The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

PLoS One. 2016 Oct 25;11(10):e0165496. doi: 10.1371/journal.pone.0165496. eCollection 2016.

Abstract

A drug's biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO) terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347), monoamine transmembrane transporter activity (GO:0008504), negative regulation of synaptic transmission (GO:0050805), neuroactive ligand-receptor interaction (hsa04080), serotonergic synapse (hsa04726), and linoleic acid metabolism (hsa00591), among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives.

MeSH terms

  • Computational Biology / methods*
  • Gene Ontology
  • Half-Life
  • Humans
  • Linoleic Acid / metabolism
  • Metabolic Networks and Pathways
  • Organic Anion Transporters / metabolism
  • Pharmaceutical Preparations / metabolism*
  • Synapses / metabolism
  • Synaptic Transmission / genetics
  • Vesicular Monoamine Transport Proteins / metabolism

Substances

  • Organic Anion Transporters
  • Pharmaceutical Preparations
  • Vesicular Monoamine Transport Proteins
  • Linoleic Acid

Grants and funding

National Natural Science Foundation of China (31371335, 61303099), Shanghai Sailing Program and The Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) (2016245). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.