S. Joshua Swamidass, MD PhD

Combined Analysis of Phenotypic and Target-Based Screening in Assay Networks

A robot arm (foreground) retrieves assay plates from incubators and places them at compound transfer stations or hands them off to another arm (background) that services liquid dispensers or plate readers.


Citation:

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.

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 onlineĀ (http://swami.wustl.edu/flow/assay_network.html).

Site: http://jbx.sagepub.com/content/early/2014/02/20/1087057114523068