Research ArticleDrug Screening

Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

Science Signaling  15 Oct 2013:
Vol. 6, Issue 297, pp. ra90
DOI: 10.1126/scisignal.2004657

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Guilt by Association

Cell-based screens routinely yield many small molecules that show promise as potential drugs. However, drug development requires identifying the targets of these molecules, a process that is often time-consuming and expensive. Potts et al. report an approach that combines the initial screening of molecules with the ability to assign putative biological functions. The expression of six genes was used as a surrogate for cell function to screen libraries of siRNAs, microRNAs, and natural products derived from marine species. Reagents were grouped together and assumed to have similar effects on cell functions if they produced similar gene signatures. This approach identified gene products and natural product compounds that regulated processes as diverse as the breakdown of intracellular components, directed cell migration, and survival signaling. Thus, this approach holds promise for facilitating future drug discovery.