PharmGKB: The Pharmacogenomics Knowledge Base
ABSTRACT The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) is an interactive tool for researchers investigating how genetic variation effects drug response. The PharmGKB web site, www.pharmgkb.org, displays genotype, molecular, and clinical primary data integrated with literature, pathway representations, protocol information, and links to additional external resources. Users can search and browse the knowledge base by genes, drugs, diseases, and pathways. Registration is free to the entire research community but subject to an agreement to respect the rights and privacy of the individuals whose information is contained within the database. Registered users can access and download primary data to aid in the design of future pharmacogenetics and pharmacogenomics studies.
- SourceAvailable from: Eric R Gamazon[Show abstract] [Hide abstract]
ABSTRACT: Alternative splicing is a major cellular mechanism in metazoans for generating proteomic diversity. A large proportion of protein-coding genes in multicellular organisms undergo alternative splicing, and in humans, it has been estimated that nearly 90 % of protein-coding genes-much larger than expected-are subject to alternative splicing. Genomic analyses of alternative splicing have illuminated its universal role in shaping the evolution of genomes, in the control of developmental processes, and in the dynamic regulation of the transcriptome to influence phenotype. Disruption of the splicing machinery has been found to drive pathophysiology, and indeed reprogramming of aberrant splicing can provide novel approaches to the development of molecular therapy. This review focuses on the recent progress in our understanding of alternative splicing brought about by the unprecedented explosive growth of genomic data and highlights the relevance of human splicing variation on disease and therapy.Human Genetics 06/2014; 133(6). DOI:10.1007/s00439-013-1411-3 · 4.52 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The genetic bases of complex traits often involve multiple inherited genetic factors that function in a network basis. By promoting or reducing the expression of functional genes that are directly or indirectly related to a trait, gene regulation has been proposed as a major determinant of trait variation. The combined analysis of genetic and gene expression data, termed genetical genomics analysis or eQTL mapping, holds great promise in disentangling the mechanism of gene regulation. Given that genes function in a network basis, the detection of a genetic system as a whole could shed novel light into the role of gene regulation. We hypothesized that gene expression changes are often caused by the regulation of a set of variants that belongs to a common genetic system (e.g., a gene network or a pathway). We proposed to combine individual signals (e.g., p-values) within a genetic system to form an overall signal while considering correlations between variants, with the goal of inferring the role of the whole system in regulating gene expression in an eQTL mapping framework. A Satterwhite approximation method is applied to approximate the distribution of the combined p-values. Both simulation and real data analysis showed the relative merits of the combined method. Our method provides a novel strategy in addressing questions related to gene regulations from a systems biology perspective.Statistics and its interface 01/2011; 4(1):381-388. DOI:10.4310/SII.2011.v4.n3.a13 · 0.46 Impact Factor
Article: Use of i.v. antibiotics at home.Community nurse 09/1996; 2(7):15-6.