Integrated systems pharmacology analysis of clinical drug-induced peripheral neuropathy

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 - Jan 1 2014

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Pharmacology
Clinical Pharmacology
Peripheral Nervous System Diseases
Integrated System
Drugs
Genes
Pharmaceutical Preparations
Proteins
Cell death
Antigens
Labels
Incidence
Target
Gene
Protein
Regression Tree
Permutation Test
Apoptosis
Tree Algorithms
Proliferating Cell Nuclear Antigen

ASJC Scopus subject areas

  • Modeling and Simulation
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Integrated systems pharmacology analysis of clinical drug-induced peripheral neuropathy. / Hur, Junguk; Guo, A. Y.; Loh, W. Y.; Feldman, E. L.; Bai, J. P.F.

In: CPT: Pharmacometrics and Systems Pharmacology, Vol. 3, No. 5, e114, 01.01.2014.

Research output: Contribution to journalArticle

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