PI-550: Pharmacogenomics and Metabolomics (2 credits)
1.Multi-omics: Basic introduction to genomics, structural and functional genomics, transcriptomics, proteomics, metabolomics, metagenomics, pharmacogenomics, immunomes and their role in drug discovery.
2.Human Genome Project: History, milestones, background and organization of HGP, how the human genome was mapped, strategies in identifying human disease genes. Genome mapping and Assembly programs (Phred, Phrap, EULER, etc), Genome analysis tools (Mummer, Geneplot, Artemis, BLASt2, MegaBlast).
3.DNA sequencing methods: Manual & automated: Maxam and Gilbert and Sanger method. Chain termination method, Pyrosequencing. Next-Generation Sequencing (NGS): Understanding of NGS and its role in bioinformatics, concepts of DNASeq, RNASeq, ChIPSeq, metagenomics, single cell sequences, data collection, processing, interpretation and quantification of NGS data, tools and software available for NGS data.
4.Biomarker Identification: Definitions, classifications, and characteristics of biomarkers, the importance of biomarkers for modern medicine and bioinformatics analysis of genomic polymorphism, recognizing functional regions in the human genome and interpreting GWAS studies, tools and techniques for identification of biomarker and target validation.
5.Metabolomics: Definition, metabolites and metabolite profiling, metabolomics vs metabonomic, targeted and untargeted metabolomics, pathway and metabolome databases. Pharmacogenomics of Phase I/II/II metabolism: CYP 450 enzyme, CYP inhibition/induction, UGT isoforms, kinetics exhibited by UGTs (inhibition/induction), efflux/influx transporters, drug resistance due to over expression of efflux transporters, substrate/inhibitor selectivity of efflux transporters, IVIVC/ in silico modelling, case studies, non CYP metabloism.
6.Reactive metabolites and drug safety: Optimizing drug candidates - Phase I, II and III metabolisms, drug metabolism and disposition profile of drugs, identification of the site of metabolism (SoM), structure metabolism relationships (SMR) and quantum chemical parameters in determining SoM, case studies.
7.PK/PD Modelling: Drug interaction (PK-PD interactions), altered pharmacokinetics, understanding concentration/ response, mechanism-based PK/PD models, simulation for study design including estimation methods and simulation methods, computer-aided simulation for predicting PK/PD.
8.Personalized medicine: Concept of personalized medicine, inter individual differences and genetic basis for variability in drug response / metabolism and susceptibility to adverse effects; gene-drug interaction; future of drug therapy. Use of Genomics in drug target identification, drug development and disease diagnosis.
9.Immunoinformatic: Applications in immunoinformatic and computational immunology, epitope prediction, design and evaluation of vaccine design, case studies
10.Multi-omics Applications: Multi-omics approaches in cancer, cancer resistance