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Sample to Insight Alexander Kaplun, PhD Sep 22 2015 1 PGMD: a comprehensive pharmacogenomic database for personalized medicine and drug discovery
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Sample to Insight Got diagnosed. Now what?
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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
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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
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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
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Sample to Insight Types of evidence
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Sample to Insight HapMap D’, LOD, and R 2 scores Computed for all PGMD sites Includes between non-PGMD sites Linkage Disequilibrium
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Sample to Insight Allele frequencies Major sources including: EVS 1000 Genomes HapMap
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Sample to Insight Delivery models Online PGMD Web Interface Download MySQL database TSV BED GFF Custom Pipeline Integration
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Sample to Insight Patient with complex genotype
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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
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Sample to Insight PGMD analysis of the patient’s exome
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Sample to Insight The result: 171 PGx variants
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Sample to Insight 54 of them are cancer therapy related
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Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER
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Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDS
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Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDS GEMCITABINE
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Sample to Insight 54 of them are cancer therapy related NON-SMALL-CELL LUNG CANCER PLATINUM COMPOUNDSGEMCITABINE BREAST CANCER
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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
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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
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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
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Sample to Insight 54 of them are cancer therapy related MULTIPLE CANCERS
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Sample to Insight 54 of them are cancer therapy related MULTIPLE CANCERS METHOTREXATE (needs higher dose) ANTHRACYCLINES (more side effects)
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Sample to Insight
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