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.