Swamidass, S. J., Schillebeeckx, C. N., Matlock, M., Hurle, M. R., & Agarwal, P. (2014). Combined Analysis of Phenotypic and Target-Based Screening in Assay Networks. Journal of biomolecular screening, 1087057114523068.
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).