1. Sample to Insight Alexander Kaplun, PhD Sep 22 2015 1 PGMD: a comprehensive pharmacogenomic database for personalized medicine and drug discovery

2. Sample to Insight Got diagnosed. Now what?

3. Sample to Insight PGMD TM Comprehensive pharmacogenomic database PGx/ADME panels FDA and EMA approved drugs containing PGx labels Associations from 6500+ publications from 500+ journals studying >1400 drugs

4. Sample to Insight A comprehensive source of PGx data Focus on peer-reviewed scientific literature Experimental results are extracted by highly trained genetic experts Content is updated 4x per year

5. Sample to Insight Facilitates mapping of variants onto genome at position or genotype level Associations from 6500+ publications from 500+ journals studying >1400 drugs Median dose requirement of warfarin in patients with CYP2C9*1/CYP2C9*3 haplotype is 2.6 mg Genotype/haplotype specific findings p-value -.001 Relative Risk, Hazards Ratio, 95% Confidence Interval when available Statistical significance 22 cases with A/C genotype, 159 subjects studied, Design - Clinical Trial Pop: European Continental Ancestry Group, Age: 24-95, Treatment: All patients are treated with 0.5 mg to 10 mg/day of warfarin Study details (All studies are in vivo) PGMD: PharmacoGenomic Mutation Database

6. Sample to Insight Types of evidence

7. Sample to Insight HapMap D’, LOD, and R 2 scores Computed for all PGMD sites Includes between non-PGMD sites Linkage Disequilibrium

8. Sample to Insight Allele frequencies Major sources including: EVS 1000 Genomes HapMap

9. Sample to Insight Delivery models Online PGMD Web Interface Download MySQL database TSV BED GFF Custom Pipeline Integration

10. Sample to Insight Patient with complex genotype

11. Sample to Insight Genome Trax™ Candidate Genes Disease causing variants Regulatory variants Over 190 million annotations total TrackRelease 2015.1 HGMD® inherited disease mutations146,581 HGMD® imputed mutations14,570 Pharmacogenomic Variants806,806 GWAS Catalogue18,735 COSMIC somatic disease mutations2,626,811 ClinVar127,638 TRANSFAC® experimentally verified TFBS15,330 ChIP-seq Transcription Factor Binding Sites9,178,528 Predicted TF@DNase I hypersensitivity sites10,732,462 miRNA gene sites2,735 PTMs (Post-Translational Modifications)35,079 PROTEOME ™ disease genes14,905 PROTEOME ™ Drug target genes2,976 PROTEOME ™ Pathway genes2,057 HGMD® disease genes27,257 SIFT &Polyphen predictions, conservation88,986,833 EVS allele frequencies3,663,071 Allele frequency from 1000 Genomes12,330,177 dbSNP common SNPs13,604,359 dbSNP60,879,061 Function prediction & frequency

12. Sample to Insight PGMD analysis of the patient’s exome

13. Sample to Insight The result: 171 PGx variants

14. Sample to Insight 54 of them are cancer therapy related

15. Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER

16. Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDS

17. Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDS GEMCITABINE

18. Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDSGEMCITABINE BREAST CANCER

19. Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDSGEMCITABINE BREAST CANCER DOCETAXEL OR OTHER TAXANES ADJUVANT AROMATASE INHIBITOR THERAPY

20. Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDSGEMCITABINE BREAST CANCER DOCETAXEL OR OTHER TAXANES ADJUVANT AROMATASE INHIBITOR THERAPY COLORECTAL CANCER

21. Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDSGEMCITABINE BREAST CANCER DOCETAXEL OR OTHER TAXANES ADJUVANT AROMATASE INHIBITOR THERAPY COLORECTAL CANCER FOLFOX PROTOCOL

22. Sample to Insight 54 of them are cancer therapy related MULTIPLE CANCERS

23. Sample to Insight 54 of them are cancer therapy related MULTIPLE CANCERS METHOTREXATE (needs higher dose) ANTHRACYCLINES (more side effects)

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