Relating drug-protein interaction network with drug side effects

Sayaka Mizutani, Edouard Pauwels, Véronique Stoven, Susumu Goto, Yoshihiro Yamanishi

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system-wide approaches for linking different scales of drug actions; namely drugprotein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the cooccurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug-targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles.

Original languageEnglish
Article numberbts383
Pages (from-to)i522-i528
JournalBioinformatics
Volume28
Issue number18
DOIs
Publication statusPublished - Sep 2012

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

Fingerprint Dive into the research topics of 'Relating drug-protein interaction network with drug side effects'. Together they form a unique fingerprint.

  • Cite this

    Mizutani, S., Pauwels, E., Stoven, V., Goto, S., & Yamanishi, Y. (2012). Relating drug-protein interaction network with drug side effects. Bioinformatics, 28(18), i522-i528. [bts383]. https://doi.org/10.1093/bioinformatics/bts383