Large-scale elucidation of drug response pathways in humans

Yael Silberberg, Assaf Gottlieb, Martin Kupiec, Eytan Ruppin, Roded Sharan

Research output: Contribution to journalArticlepeer-review

Abstract

Elucidating signaling pathways is a fundamental step in understanding cellular processes and developing new therapeutic strategies. Here we introduce a method for the large-scale elucidation of signaling pathways involved in cellular response to drugs. Combining drug targets, drug response expression profiles, and the human physical interaction network, we infer 99 human drug response pathways and study their properties. Based on the newly inferred pathways, we develop a pathway-based drug-drug similarity measure and compare it to two common, gold standard drug-drug similarity measures. Remarkably, our measure provides better correspondence to these gold standards than similarity measures that are based on associations between drugs and known pathways, or on drug-specific gene expression profiles. It further improves the prediction of drug side effects and indications, elucidating specific response pathways that may be associated with these drug properties. Supplementary Material for this article is available at www.liebertonline.com/cmb.

Original languageEnglish
Pages (from-to)163-174
Number of pages12
JournalJournal of Computational Biology
Volume19
Issue number2
DOIs
StatePublished - 1 Feb 2012

Keywords

  • algorithms
  • gene networks
  • graphs and networks
  • paths

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