1. Overview of Bioinformatics A/P Shoba Ranganathan Justin Choo National University of Singapore A Tutorial on Bioinformatics

2. What is Bioinformatics ? Bioinformatics is “the study of the information content and information flow in biological systems and processes”. - Michael Liebman in “Bioinformatics: An Editorial Perspective” (http://www.netsci.org/Science/Bioinform/feature01.html) Annotate -> store -> search/retrieve -> analyze -> visualize Nucleic acid sequence (genes and RNAs), protein sequence and structural information.

3. SARS & Its Implication...

4. SARS - Bioinformatics In Action

5. Sequencing Of SARS … Photo above shows the sequencing area of the lab. Taken from http://www.bcgsc.ca/bioinfo/SARS/

6. Partial Sequence of SARS … >gi|30248028|gb|AY274119.3| SARS coronavirus TOR2, complete genome ATATTAGGTTTTTACCTACCCAGGAAAAGCCAACCAACCTCGATCTCTTGTAGATCTGTTCTCTAAACGA ACTTTAAAATCTGTGTAGCTGTCGCTCGGCTGCATGCCTAGTGCACCTACGCAGTATAAACAATAATAAA TTTTACTGTCGTTGACAAGAAACGAGTAACTCGTCCCTCTTCTGCAGACTGCTTACGGTTTCGTCCGTGT TGCAGTCGATCATCAGCATACCTAGGTTTCGTCCGGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTTC TTGGTGTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTCCTTCAGGTTAGAGACGTGCTAGTGCG TGGCTTCGGGGACTCTGTGGAAGAGGCCCTATCGGAGGCACGTGAACACCTCAAAAATGGCACTTGTGGT CTAGTAGAGCTGGAAAAAGGCGTACTGCCCCAGCTTGAACAGCCCTATGTGTTCATTAAACGTTCTGATG CCTTAAGCACCAATCACGGCCACAAGGTCGTTGAGCTGGTTGCAGAAATGGACGGCATTCAGTACGGTCG TAGCGGTATAACACTGGGAGTACTCGTGCCACATGTGGGCGAAACCCCAATTGCATACCGCAATGTTCTT CTTCGTAAGAACGGTAATAAGGGAGCCGGTGGTCATAGCTATGGCATCGATCTAAAGTCTTATGACTTAG GTGACGAGCTTGGCACTGATCCCATTGAAGATTATGAACAAAACTGGAACACTAAGCATGGCAGTGGTGC ACTCCGTGAACTCACTCGTGAGCTCAATGGAGGTGCAGTCACTCGCTATGTCGACAACAATTTCTGTGGC CCAGATGGGTACCCTCTTGATTGCATCAAAGATTTTCTCGCACGCGCGGGCAAGTCAATGTGCACTCTTT CCGAACAACTTGATTACATCGAGTCGAAGAGAGGTGTCTACTGCTGCCGTGACCATGAGCATGAAATTGC CTGGTTCACTGAGCGCTCTGATAAGAGCTACGAGCACCAGACACCCTTCGAAATTAAGAGTGCCAAGAAA TTTGACACTTTCAAAGGGGAATGCCCAAAGTTTGTGTTTCCTCTTAACTCAAAAGTCAAAGTCATTCAAC CACGTGTTGAAAAGAAAAAGACTGAGGGTTTCATGGGGCGTATACGCTCTGTGTACCCTGTTGCATCTCC ACAGGAGTGTAACAATATGCACTTGTCTACCTTGATGAAATGTAATCATTGCGATGAAGTTTCATGGCAG ACGTGCGACTTTCTGAAAGCCACTTGTGAACATTGTGGCACTGAAAATTTAGTTATTGAAGGACCTACTA............... The complete genome of SARS, obtained from http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?30248028:NCBI:4812069

7. Bioinformatics -Timeline 1980 2005 2000 1990 1985 1995 Single Structures Modeling & Geometry Forces & Simulation Docking Sequences, Sequence-Structure Relationships Alignment Structure Prediction Fold recognition Genomics Dealing with many sequences Gene finding & Genome Annotation Databases Integrative Analysis Expression & Proteomics Data Data mining Simulation again…(whole cells?).

8. Biological Databases Collect, organise and classify data Query the dataset Retrieve entries based on keyword search Genbank PDB EMBL

9. Sequence Analysis Software What is the information contained in a biological sequence? How can we analyse it to gain knowledge? Does it contain any functional clues?

10. Sequence Comparison How can we compare a given sequence to the millions in the database? Which ones are truly related by evolution? What can the study of related sequences tell us?

11. Sequence Alignment After collecting a set of related sequences, how can we compare them as a set? How should we line up the sequences so that the most similar portions are together? What do we do with sequences of different lengths?

12. Protein Structure The function of a protein is a consequence of its folded state: Anfinsen, 1961 The 3D fold of a protein is called its structure In 3D, the business end of the protein has contributions from different regions of its sequence Picture taken from http://www.strgen.org/

13. Visualization Using graphic tools to view structures Simple commands to analyse structures and active sites Different graphic representations and colouring schemes Picture taken from http://www.nature.com/

14. Careers in Bioinformatics Genomics: Genome sequencing of –Bacteria, viruses –Animals –Plants Comparative genomics Annotation and Mapping Gene Discovery

15. Careers in Bioinformatics Functional Genomics (Gene Expression and Regulation): Control Regions –Switches –Circuits –Bypass –Feedback loops Environmental Effects Diseased States Chemical Consequences

16. Careers in Bioinformatics Pharmacogenomics: SNPs –Regional, ethnic variations –Inheritance patterns –Radiological/ecological modifications Therapeutic target recognition Correlation of drug and expression effects Pathway Effects

17. Careers in Bioinformatics Proteomics: Protein Profiling –Alternate splice variants –Orphan genes –Cryptic introns Gene Therapy

18. Careers in Bioinformatics Structural Genomics: Experimental Protein structures –Apo state –Holo state –Structural modifications Membrane Proteins Homology Modelling Comparative Modelling

19. Careers in Bioinformatics Drug and Vaccine Design: Screening Natural Products –Plants –Fungi –Bacteria Chemicals In silico modifications of ligands Vaccine design and delivery

20. Job Sectors Academia Research Institutes Biotechnology Bioinformatics Pharmaceutical Agriculture Biodiversity

21. The End