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Predicting Highly Connected Proteins in PIN using QSAR Art Cherkasov Apr 14, 2011 UBC / VGH THE UNIVERSITY OF BRITISH COLUMBIA.

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Presentation on theme: "Predicting Highly Connected Proteins in PIN using QSAR Art Cherkasov Apr 14, 2011 UBC / VGH THE UNIVERSITY OF BRITISH COLUMBIA."— Presentation transcript:

1 Predicting Highly Connected Proteins in PIN using QSAR Art Cherkasov Apr 14, 2011 UBC / VGH artc@interchange.ubc.ca THE UNIVERSITY OF BRITISH COLUMBIA

2 Chemical Space: Navigation(Grouping) THE UNIVERSITY OF BRITISH COLUMBIA What is Chem(o)informatics ???

3 Chemical Space: Navigation(Grouping) THE UNIVERSITY OF BRITISH COLUMBIA What is Chem(o)informatics ??? hits GARBAGE hits + GARBAGE

4 Chemical Space: Navigation(Grouping) THE UNIVERSITY OF BRITISH COLUMBIA What is Chem(o)informatics ??? hits GARBAGE hits + GARBAGE Docking works? Target Structure? LIGAND-BASED METHODS STRUCTURE -BASED METHODS De Novo works? + + +- - - Traditional Drug Design Modes

5 Multiple Test Sets Multiple Test Sets Y-randomization Combi-QSAR Modeling Combi-QSAR Modeling Activity Prediction Activity Prediction Only accept models that have Q 2 > 0.6 R 2 > 0.6 etc. Only accept models that have Q 2 > 0.6 R 2 > 0.6 etc. External validation Using Applicability Domain External validation Using Applicability Domain Split into Training, Test and External Validation sets Split into Training, Test and External Validation sets Experimental Validation Experimental Validation Database Screening Using Applicability Domain Database Screening Using Applicability Domain Validated Predictive Models with High Internal & External Accuracy Validated Predictive Models with High Internal & External Accuracy *Tropsha, A. Best Practices for QSAR Model Development, Validation, and Exploitation Mol. Inf., 2010, 29, 476 – 488 CHEMBENCH.MML.UNC.EDU Predictive QSAR Modeling Workflow* is complex Original Dataset Original Dataset Multiple Training Sets Multiple Training Sets

6 THE UNIVERSITY OF BRITISH COLUMBIA Cheminformatics ??? hits GARBAGE hits + GARBAGE Docking works? Target Structure? LIGAND-BASED METHODS STRUCTURE -BASED METHODS De Novo works? + + +- - - Traditional Drug Design Modes QSAR, FP similarity, Clustering, MolFields, etc

7 THE UNIVERSITY OF BRITISH COLUMBIA Cheminformatics !!! hits GARBAGE hits + GARBAGE Docking works? LIGAND-BASED METHODS STRUCTURE -BASED METHODS De Novo works? + + - - Conventional Drug Design Modes

8 from A. Cherkasov & A. Tropsha, Nature Drug Discovery Reviews, 2011 (in progress) QSAR – “Quantitative Structure-Activity Relationships” PubMed Citations THE UNIVERSITY OF BRITISH COLUMBIA

9 specifics of the talk: 1. Chemical Space: Quantification (Modeling ) and Navigation (Grouping) a. Ligand QSAR:: Concept:Consensus Modeling b. Ligand QSAR: :Examples: BML Model, Antibiotics 2. Peptide QSAR: :Example: Antimicrobial Peptides 3. Protein QSAR: :Example:“Hubs” in PINs THE UNIVERSITY OF BRITISH COLUMBIA

10 Quantitative Structure Activity Relationships D E S C R I P T O R S 0.613 0.380 -0.222 0.708 1.146 0.491 0.301 0.141 0.956 0.256 0.799 1.195 1.005 Principles of QSAR modeling: Compounds, Descriptors, Functions, Activity COMPOUNDSCOMPOUNDS ACTIVITYACTIVITY Slide by A. Tropsha, 2010

11 Quantitative Structure Property Relationships D E S C R I P T O R S 0.613 0.380 -0.222 0.708 1.146 0.491 0.301 0.141 0.956 0.256 0.799 1.195 1.005 COMPOUNDSCOMPOUNDS PROPERTYPROPERTY Principles of QSAR modeling: Compounds, Descriptors, Functions, Activity Slide by A. Tropsha, 2010

12 THE UNIVERSITY OF BRITISH COLUMBIA 10 40 - 10 120 compounds with C, H, O, N, P, S, F, Cl, Br, I, and MW < 500 ?? Compounds : Chemical Universe

13 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA. THE UNIVERSITY OF BRITISH COLUMBIA Descriptors: “Inductive” etc

14 THE UNIVERSITY OF BRITISH COLUMBIA Functions: MLR, PLS, kNN, SVM, ANN, Binary Regression, Decision Tree, RandomForest, PCA, Hybrid Methods, LDA, etc

15 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Activity: Continuous, Binary Molecular structure gets translated into numbers (descriptors) THE UNIVERSITY OF BRITISH COLUMBIA f ( Descriptors) ~ Activity Activity: Continuous Binary

16 Chemical Space: Activity (Property) Quantification THE UNIVERSITY OF BRITISH COLUMBIA

17 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA THE UNIVERSITY OF BRITISH COLUMBIA EXAMPLE: QSAR TOX CONSENSUS MODELING:2008

18 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA THE UNIVERSITY OF BRITISH COLUMBIA Group ID Modeling Techniques Descriptor TypeApplicability Domain Definition UNCkNN, SVMMolconnZ, Dragon Euclidean distance threshold between a test compound and compounds in the modeling set ULP MLR, SVM, kNN Fragments (ISIDA), Molecular (CODESSA-Pro) Euclidean distance threshold between a compound and compounds in the modeling set; bounding box UIMLR/OLSDragonLeverage approach UKPLSDragon Residual standard deviation and leverage within the PLSR model VCCLABASNNE-state indices Maximal correlation coefficient of the test molecule to the training set molecules in the space of models UBC MLR, ANN, SVM, PLS IND_I Range of independent variables values in the training set +/- 15% Overview of QSAR modeling approaches employed by six cheminformatic groups involved in this study.

19 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA THE UNIVERSITY OF BRITISH COLUMBIA ModelGroup ID Modeling Set (n=644)Validation Set I (n=339)Validation Set II (n=110) Q 2 abs MAE Coverage (%) R 2 abs MAE Coverage (%) R 2 abs MAE Coverage (%) kNN-DragonUNC0.920.221000.850.2780.20.720.3352.7 kNN- MolconnZ UNC0.910.2399.80.840.3084.30.440.3953.6 SVM-DragonUNC0.930.211000.810.3180.20.830.2752.7 SVM- MolconnZ UNC0.890.251000.830.3084.30.550.3753.6 ISIDA-kNNULP0.770.371000.730.3678.50.630.3742.7 ISIDA-SVMULP0.950.151000.760.321000.380.50100 ISIDA-MLRULP0.940.201000.810.3195.90.650.4151.8 CODESSA- MLR ULP0.720.421000.710.441000.580.47100 OLSUI0.860.3092.10.770.3597.00.590.4398.2 PLSUK0.880.2897.70.810.3496.10.590.4095.5 ASNNVCCLAB0.830.3183.90.870.2887.40.750.3271.8 PLS-IND_IUBC0.760.391000.740.3999.70.450.54100 MLR-IND_IUBC0.770.391000.750.4099.70.460.53100 ANN-IND_IUBC0.770.391000.760.3999.70.460.53100 SVM-IND_IUBC0.790.311000.790.3599.70.530.46100

20 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA THE UNIVERSITY OF BRITISH COLUMBIA ModelGroup ID Modeling Set (n=644)Validation Set I (n=339)Validation Set II (n=110) Q 2 abs MAE Coverage (%) R 2 abs MAE Coverage (%) R 2 abs MAE Coverage (%) kNN-DragonUNC0.920.221000.850.2780.20.720.3352.7 kNN- MolconnZ UNC0.910.2399.80.840.3084.30.440.3953.6 SVM-DragonUNC0.930.211000.810.3180.20.830.2752.7 SVM- MolconnZ UNC0.890.251000.830.3084.30.550.3753.6 ISIDA-kNNULP0.770.371000.730.3678.50.630.3742.7 ISIDA-SVMULP0.950.151000.760.321000.380.50100 ISIDA-MLRULP0.940.201000.810.3195.90.650.4151.8 CODESSA- MLR ULP0.720.421000.710.441000.580.47100 OLSUI0.860.3092.10.770.3597.00.590.4398.2 PLSUK0.880.2897.70.810.3496.10.590.4095.5 ASNNVCCLAB0.830.3183.90.870.2887.40.750.3271.8 PLS-IND_IUBC0.760.391000.740.3999.70.450.54100 MLR-IND_IUBC0.770.391000.750.4099.70.460.53100 ANN-IND_IUBC0.770.391000.760.3999.70.460.53100 SVM-IND_IUBC0.790.311000.790.3599.70.530.46100 Consensus Model I a -0.920.231000.850.291000.670.39100 Consensus Model II b -0.920.221000.870.271000.700.34100 Consensus Model IIB c -0.920.221000.870.271000.700.36100 Consensus Model III d -0.920.221000.860.2899.70.700.3498.2

21 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA THE UNIVERSITY OF BRITISH COLUMBIA

22 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA THE UNIVERSITY OF BRITISH COLUMBIA QSAR CONSENSUS MODELING:2010

23 23 Geography of collaboration 40 scientists, 15 institutions Slide by A. Tropsha, 2011

24 Chemical Space: Navigation(Grouping) THE UNIVERSITY OF BRITISH COLUMBIA

25

26

27 MEDICINE INFECTIOUS DISEASES THE UNIVERSITY OF BRITISH COLUMBIA

28 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA db50 THE UNIVERSITY OF BRITISH COLUMBIA

29 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA MERCK Database QSAR annotation as Antibiotics and BML THE UNIVERSITY OF BRITISH COLUMBIA

30 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA CONFIRMED CONFIRMED CONFIRMED THE UNIVERSITY OF BRITISH COLUMBIA MERCK Database QSAR annotation as Antibiotics and BML

31 THE UNIVERSITY OF BRITISH COLUMBIA `

32 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA THE UNIVERSITY OF BRITISH COLUMBIA A number of QSAR models have been elaborated to separate individual clusters within the dataset of 958 human therapeutics, 519 antimicrobials, 1202 drug-like chemicals, as well as 1102 human-, 551 bacterial-, 2351 plant- and 825 fungal metabolites. Antimicrobials from Drugs Antimicrobials from Drug-likes Distinguishing Antimicrobials from all others Distinguishing Antimicrobials versus Drugs versus Drug- likes QSAR model for Bacterial Metabolites TrainTestTrainTestTrainTestTrainTestTrainTest T_P32713033214029412427089360139 T_N63124884134214906211486644792347 F_P4933714322017143926 F_N333530236641108584819 SPEC0.930.880.990.960.980.970.990.980.950.93 SENS0.910.790.920.860.820.750.710.610.88 ACCUR0.920.850.970.930.950.920.930.910.930.92 PPV0.870.800.980.910.900.860.940.860.900.84 NPV0.950.880.970.940.960.940.930.920.940.95

33 Separation of various classes of substances in the chemical space Antibacterials Inactive Chemicals General drugs Bacterial metabolites THE UNIVERSITY OF BRITISH COLUMBIA

34 The two acyl hydrazone-based in silico hits with potent selective inhibitory activity towards MRSA Pyruvate Kinase. IC 50 (mM) Growth inhibition (%) Compound StructureMRSA PK Human M1 PK Human M2 PK Human R PK Human L PK S. aureus HeLa IS-63 0.85 450 519 450 38 10 13 FP search of ZINC db with BML scoring THE UNIVERSITY OF BRITISH COLUMBIA

35 The two acyl hydrazone-based in silico hits with potent selective inhibitory activity towards MRSA Pyruvate Kinase. IC 50 (mM) Growth inhibition (%) Compound StructureMRSA PK Human M1 PK Human M2 PK Human R PK Human L PK S. aureus HeLa IS-63 0.85 450 519 450 38 10 13 IS-130 0.091 375 125 350 350 35 0 THE UNIVERSITY OF BRITISH COLUMBIA

36 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA b aGOGOf   )( Pareto’s inequality law introduced more then a century ago (Pareto, 1897 ) economic-, professional-, sexual- and social networks airline routing power lines connections language networks internet hyperlinks protein interactomes brain organization metabolic pathways food and ecological webs 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0100200300400500 Power law Weibull analytical Weibull by plotting experiment THE UNIVERSITY OF BRITISH COLUMBIA

37 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Most common distinct molecular scaffolds classified for the studied groups of chemical substances THE UNIVERSITY OF BRITISH COLUMBIA

38 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Most common distinct substituents classified for the studied groups of chemical substances THE UNIVERSITY OF BRITISH COLUMBIA

39 GoingBigger -> Peptide QSAR:: Antimicrobial Peptides THE UNIVERSITY OF BRITISH COLUMBIA

40 Bad Bugs Need Drugs: IDSA, March 2006 Antimicrobial Availability Task Force Widespread prevalence of MDR bacteria in hospitals Few drugs in a pipeline, Urgent need for R&D Experts Fear Increase in Drug-resistant Infectious Here: Globe and Mail, March 2006 MRSA, a treatment-resistant form of bacteria that spreads through direct contact, is called a greater threat to public health than SARS or bird flu. The Boston Globe, August 21, 2006 THE UNIVERSITY OF BRITISH COLUMBIA

41 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Antimicrobial Peptides (AMP) Modes of Action Oren and Shai (Biopolymers 1998) 8-50 AA long, gene-coded, often contain lead sequence, parts of innate immunity THE UNIVERSITY OF BRITISH COLUMBIA

42 Factors Influencing activity of AMP’s: Usually helical, but can be beta, cyclic, irregular, induced IKWLKIFL THE UNIVERSITY OF BRITISH COLUMBIA

43 Factors Influencing activity of AMP’s: Hydrophobicity, Positive Charge, two-phased IKWLKIFLBUT: 9^20 possible sequence variants!!! THE UNIVERSITY OF BRITISH COLUMBIA

44 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Sources of antibiotic peptides SWISS-PROT database: ftp://ftp.ebi.ac.uk/pub/databases/swissprot/release/sprot42.dat University of Nebraska Medical Center: http://aps.unmc.edu/AP/main.php http://aps.unmc.edu/AP/main.php Biochemistry Department University of Triest, Italy: http://www.bbcm.units.it/~tossi/pag5.htm http://www.bbcm.units.it/~tossi/pag5.htm National Library of Health Sciences, TERKKO, University of Helsinki: http://oma.terkko.helsinki.fi:8080/~SAPD/login School of Crystallography, Birkbeck University of London: http://www.cryst.bbk.ac.uk/peptaibol/peptaibol_database_1lettercodes.htm http://www.cryst.bbk.ac.uk/peptaibol/peptaibol_database_1lettercodes.htm THE UNIVERSITY OF BRITISH COLUMBIA

45 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Examples of typical gene-coded AMPs: beta-Defensins, alpha-Defensins Cecropins, Cholecystokinins Stomoxyns, Gastrins, Transferrins, Magainins, Brevinins, Xenopsins Dermaseptins, Provicilins Cupiennines, Vicilins, Corticostatins, Apidaecin, Cathelicidin, Statherins, Histatins Bombinins, Dermaseptins, Maximins, Dermadistinctins, Maculatina, Caerins, Aureins, Citropin, Waglerins, Gastrins, Cholecystokinins, Magainins, Xenopsins non -TOXIC non - IMMUNOGENIC do not cause RESISTANCE fast and broadly ACTIVE THE UNIVERSITY OF BRITISH COLUMBIA

46 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Examples of typical gene-coded AMPs: beta-Defensins, alpha-Defensins Cecropins, Cholecystokinins Stomoxyns, Gastrins, Transferrins, Magainins, Brevinins, Xenopsins Dermaseptins, Provicilins Cupiennines, Vicilins, Corticostatins, Apidaecin, Cathelicidin, Statherins, Histatins Bombinins, Dermaseptins, Maximins, Dermadistinctins, Maculatina, Caerins, Aureins, Citropin, Waglerins, Gastrins, Cholecystokinins, Magainins, Xenopsins non -TOXIC non - IMMUNOGENIC do not cause RESISTANCE fast and broadly ACTIVE BIOINFORMATICS APPROACHES TO MODELING AMPs ALL FAILED! THE UNIVERSITY OF BRITISH COLUMBIA

47 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Designed Cheminformatics pipeline for AMPs 2020 100,000 THE UNIVERSITY OF BRITISH COLUMBIA

48 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Training set Top % as actives AccuracySpecificitySensitivity Positive Predictive Value A 5%0.960.980.620.58 10%0.930.940.760.39 25%0.78 0.850.17 B 5%0.940.970.330.30 10%0.880.900.330.12 25%0.77 0.800.12 A+B 5%0.950.970.47 10%0.910.920.540.27 25%0.760.770.660.13 10 cross Trained statistics for AMPs QSAR models THE UNIVERSITY OF BRITISH COLUMBIA

49 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA 100,000 PEPTIDES have been designed using random sequence composition with ongoing enrichment for key aminoacids Subjected to QSAR and 20 AMPs Synthesized and TESTED THE UNIVERSITY OF BRITISH COLUMBIA

50 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA SRANDARD USED: Compound MX-226 (aka MBI-226, omiganan) ILRWPWPWRRK - prevention of wounds - burn -device-related infections (central venous catheter related infections) In Phase III-b clinical trials by MIGENIX© THE UNIVERSITY OF BRITISH COLUMBIA

51 Pseudomonas aeruginosa, Pseudomonas maltophilia, Staphylococcus aureus, Enterobacter cloacae THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE INFECTIOUS DISEASES 100,000 randomly designed, 20 tested from Q1-Q4 (predicted high-, medium-, and low-actives EX VIVO against 12 bacterial strains (uM) THE UNIVERSITY OF BRITISH COLUMBIA

52 Pseudomonas aeruginosa, Pseudomonas maltophilia, Staphylococcus aureus, Enterobacter cloacae THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE INFECTIOUS DISEASES THE UNIVERSITY OF BRITISH COLUMBIA

53 Pseudomonas aeruginosa, Pseudomonas maltophilia, Staphylococcus aureus, Enterobacter cloacae THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE INFECTIOUS DISEASES THE UNIVERSITY OF BRITISH COLUMBIA

54 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA ACTIVITY CHARGE H 2 0 – phobic moment H 2 0 – phobicity PROPERTIES DISTRIBUTIONS AMONG HIGH-, MEDIUM- AND LOW- ACTIVES THE UNIVERSITY OF BRITISH COLUMBIA

55 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Untreated THE UNIVERSITY OF BRITISH COLUMBIA

56 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA Treated THE UNIVERSITY OF BRITISH COLUMBIA

57 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA TOXICITY THE UNIVERSITY OF BRITISH COLUMBIA

58 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA IN VIVO Ability of new antimicrobial peptides HHC-10 and HHC-36 to protect mice against S. aureus infections. Bacterial loads in the peritoneal lavage from individual mice after 24 h of infection. Dead animals were assigned the highest CFU count obtained in the experiment. The solid line represents the arithmetic mean for each group. `` THE UNIVERSITY OF BRITISH COLUMBIA

59 GoingEvenBigger -> Protein QSAR THE UNIVERSITY OF BRITISH COLUMBIA

60 Protein interaction networksare scale-free networks The web of human sexual contacts (Liljeros et al., Nature, 411 (2001) 907. The food network Neurons connections THE UNIVERSITY OF BRITISH COLUMBIA

61 MRSA Proteins Interactions Network 2D representation of the developed MRSA PIN. Hub proteins are marked in yellow and non-hubs are in blue. The conventional antimicrobial targets are marked in red if they are also non-hubs. The conventional antimicrobial targets are marked in pink if they are also hubs. THE UNIVERSITY OF BRITISH COLUMBIA

62 MRSA Proteins Interactions Network TASK: to sample the network with fewest experiments? THE UNIVERSITY OF BRITISH COLUMBIA HUBS !

63 Training / Testing setE. coliS. cerevisiae D. melanogaster H. sapiens # of proteins2860539769356592 # of hubs (10% of total proteins)286535628620 # of non-hubs (90% of total proteins)2574486263075972 # of protein interactions13888371671999419115 minimum # of interactions per hub20331613 A summary of protein interaction data used in the training and testing of the hub classifiers THE UNIVERSITY OF BRITISH COLUMBIA

64 Query speciesSubject species E. coli S. cerevisiae D. melanogaster H. sapiens E. coli % of hubs with similar proteins18.18%15.03%18.18% % of non-hubs with similar proteins8.00%5.67%5.75% % of conserved hubs4.20%1.05%2.80% % of conserved non-hubs6.72%5.56%5.36% S. cerevisiae % of hubs with similar proteins7.48%34.02%39.44% % of non-hubs with similar proteins3.78%10.98%11.74% % of conserved hubs3.55%6.36%10.28% % of conserved non-hubs2.88%10.22%10.26% D. melanogaster % of hubs with similar proteins1.27%12.26%23.89% % of non-hubs with similar proteins1.93%9.75%20.64% % of conserved hubs1.11%6.69% % of conserved non-hubs1.43%7.23%17.82% H. sapiens % of hubs with similar proteins2.58%22.10%37.90% % of non-hubs with similar proteins2.28%12.34%24.55% % of conserved hubs1.94%10.00%9.35% % of conserved non-hubs1.62%8.98%21.78% Hub proteins conservation among species

65

66

67 IndexQSAR descriptors 1number of residues 2molecular weight 3-22fraction of each residues in sequence 23fraction of polar residues in sequence 24fraction of hydrophobic residues 25fraction of charged residues 26net charge at pH = 7.0 27 average hydrophobicity,  G trans (kcal/mol) 28 average “hydrophilicity”,  G app (kcal/mol) 29fraction of surface residues in sequence 30estimated surface area 31estimated volume 32-51fraction of each residue at surface 52fraction of polar residues at surface 53fraction of hydrophobic residues at surface 54fraction of charged residues at surface 55net surface charge 56average surface hydrophobicity 57average surface hydrophilicity 58ratio of average surface hydrophobicity to average hydrophobicity for sequence 59ratio of average surface “hydrophilicity” to average hydrophilicity for sequence 60isoelectric point (elementary charge unit) 61isoelectric point of surface (elementary charge unit) 62fraction of random coil residues 63fraction of α-helix residues 64 fraction of  -sheet residues 65helix-to-coil ratio for surface – helix-to-coil ratio for sequence 66average surface polarizability (kcal/mol) 67average surface MEP (kcal/mol) 68average surface ionization potential (kcal/mol) 69average surface electron affinity (kcal/mol) 70average surface electronegativity (kcal/mol) 71number of coil stretches > 4 residues in length 72length of longest contiguous coil stretch 73fraction of flexible coil residues in sequence 74fraction of flexible residues at surface 75average flexibility index for coil residues at the surface THE UNIVERSITY OF BRITISH COLUMBIA

68 E. coli hub classifier Four-fold cross-validation average performance Training sensitivityspecificityaccuracyPPVNPV 86.71%91.60%91.11%53.41%98.41% Testing sensitivityspecificityaccuracyPPVNPV 51.40%88.19%84.51%32.59%94.23% S. cerevisiae hub classifier Four-fold cross-validation average performance Training sensitivityspecificityaccuracyPPVNPV 84.36%88.99%88.53%45.74%98.10% Testing sensitivityspecificityaccuracyPPVNPV 62.99%86.16%83.86%33.37%95.49% D. melanogaster hub classifier Four-fold cross-validation average performance Training sensitivityspecificityaccuracyPPVNPV 74.95%87.24%86.12%36.90%97.22% Testing sensitivityspecificityaccuracyPPVNPV 41.24%83.86%80.00%20.28%93.48% H. sapiens hub classifier Four-fold cross-validation average performance Training sensitivityspecificityaccuracyPPVNPV 51.77%91.31%87.59%38.21%94.80% Testing sensitivityspecificityaccuracyPPVNPV 26.61%88.78%82.93%19.76%92.10% THE UNIVERSITY OF BRITISH COLUMBIA

69

70

71 MRSA Proteins Interactions Network THE UNIVERSITY OF BRITISH COLUMBIA Bait coverage summary and conserved interactions for MRSA and other PIN datasets. nr = non-redundant. * Percentages were calculated with respect to the subject species.

72 TakeHomeMessages { -> QSAR allows sampling and navigating through Chemical Space as well as modeling complex mol properties -> When done properly, QSAR can handle even unconventional systems like peptides -> QSAR methodology can/should substitute sequence- based ideology (bioinformatics) on many levels } THE UNIVERSITY OF BRITISH COLUMBIA

73 GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTAC CCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTA CTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTG GGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACT CATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAA GATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCT TGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTC TTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCT CAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGA GTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGAC CTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTC TGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGAC CTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGG TGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGT TCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCG GGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCT CCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGC AGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACT CCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACG GCACTTCTAATTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCA GGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCC TGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCAC ATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATG ATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGC TGATGATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAA TCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAAT CAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCA GCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGAC GAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACAT CAGGCTCTGACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGATGGAGCTTCCCCCTTGAGTCG GGCTGCTGAAGGGGGGTAGGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACAGTGCTGGCATCA GGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGGCTT CTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCAC AAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAG GGCACAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCA TAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGGCAGCCAGTGCCACC ATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCATGAGGCCG TTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTG GCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACC GGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCC AAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACA TTTGCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCG GAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTCTAAC TCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCAC TCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTT TCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGT GAAGGAGGGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTG GACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCATGTTGAA UBC I.D., Microbiology CIHR/MSFHR Bioinformatics CIHR V.I.D.O. U.Sask. Saskatoon, SK Genome Canada, Genome BC THE UNIVERSITY OF BRITISH COLUMBIA Lab: Michael Hsing Simon Chan Nels Thorstein Chris Fjell Fuqiang Ban Melian Huang Ken Bydler Osvaldo Santos-Filho P. Axiero Evgeny Maksakov UBC Microbiology REW Hancock K Hilpert H Jenssen U.Sask VIDO: L Babuick & team SFU Computer Sciences C. Sahinalp E. Karakoc F. Hormozdiari UBC/VGH Prostate Centre


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