Combined analysis of phenotypic and target-based screening in assay networks

S. Joshua Swamidass, Constantino N. Schillebeeckx, Matthew Matlock, Mark R. Hurle, Pankaj Agarwal

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Small-molecule screens are an integral part of drug discovery. Public domain data in PubChem alone represent more than 158 million measurements, 1.2 million molecules, and 4300 assays. We conducted a global analysis of these data, building a network of assays and connecting the assays if they shared nonpromiscuous active molecules. This network spans both phenotypic and target-based screens, recapitulates known biology, and identifies new polypharmacology. Phenotypic screens are extremely important for drug discovery, contributing to the discovery of a large proportion of new drugs. Connections between phenotypic and biochemical, target-based screens can suggest strategies for repurposing both small-molecule and biologic drugs. For example, a screen for molecules that prevent cell death from a mutated version of superoxide-dismutase is linked with ALOX15. This connection suggests a therapeutic role for ALOX15 inhibitors in amyotrophic lateral sclerosis. An interactive version of the network is available online (http://swami.wustl.edu/ flow/assay-network.html).

Original languageEnglish
Pages (from-to)782-790
Number of pages9
JournalJournal of Biomolecular Screening
Volume19
Issue number5
DOIs
StatePublished - Jun 2014

Keywords

  • Chemoinformatics
  • Database and data management
  • Pharmacology: ligand binding
  • Phenotypic drug discovery
  • Receptor binding
  • Statistical analyses

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