Integrated systems pharmacology analysis of clinical drug-induced peripheral neuropathy

J. Hur, A. Y. Guo, W. Y. Loh, E. L. Feldman, J. P.F. Bai

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

A systems pharmacology approach was undertaken to define and identify the proteins/genes significantly associated with clinical incidence and severity of drug-induced peripheral neuropathy (DIPN). Pharmacological networks of 234 DIPN drugs, their known targets (both intended and unintended), and the intermediator proteins/genes interacting with these drugs via their known targets were examined. A permutation test identified 230 DIPN-associated intermediators that were enriched with apoptosis and stress response genes. Neuropathy incidence and severity were curated from drug labels and literature, and were used to build a predictive model of DIPN using a regression tree algorithm, based on the drug targets and their intermediators. DIPN drugs whose targets interacted with both v-myc avian myelocytomatosis viral oncogene homolog (MYC) and proliferating cell nuclear antigen-associated factor (PAF15) were associated with a neuropathy incidence of 38.1%, whereas drugs interacting only with MYC had an incidence of 2.9%. These results warrant further investigation in order to develop a predictive tool for the DIPN potential of a new drug.

Original languageEnglish (US)
Article numbere114
JournalCPT: Pharmacometrics and Systems Pharmacology
Volume3
Issue number5
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

  • Modeling and Simulation
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Integrated systems pharmacology analysis of clinical drug-induced peripheral neuropathy'. Together they form a unique fingerprint.

  • Cite this