title: Functional mapping of drug response with pharmacodynamic-pharmacokinetic principles.
abstract: Recent research in pharmacogenomics has inspired our hope to predict drug response by linking it with DNA information extracted from the human genome. However, many genetic models of drug response do not incorporate biochemical principles of host-drug interactions, limiting the effectiveness of the predictive models. We argue that functional mapping, a computational tool aimed at identifying genes and genetic networks that control dynamic traits, can help explain the detailed genetic architecture of drug response by incorporating pharmacokinetic and pharmacodynamic processes. Functional mapping is particularly powerful in determining the genetic commonality and differences of drug efficacy vs. drug toxicity and drug sensitivity vs. drug resistance. We pinpoint several future directions in which functional mapping can be coupled with systems biology to unravel the genetic and metabolic machinery of drug response.
authors.affiliation: Center for Statistical Genetics, Pennsylvania State University, Hershey, PA 17033, USA.
authors.forename: Kwangmi
authors.initials: K
authors.lastname: Ahn
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Luo
authors.forename: Arthur
authors.initials: A
authors.lastname: Berg
authors.forename: David
authors.initials: D
authors.lastname: Keefe
authors.forename: Rongling
authors.initials: R
authors.lastname: Wu
mesh_terms: D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D019454:Chronotherapy; D003198:Computer Simulation; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D000069437:Pharmacological Phenomena; D040641:Quantitative Trait Loci; D016896:Treatment Outcome
chemical_list: D054316:Biomarkers, Pharmacological; D004364:Pharmaceutical Preparations