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Pathway and network-based strategies to translate genetic discoveries into effective therapies

By Casey S. Greene, Benjamin F. Voight

Posted 03 May 2016
bioRxiv DOI: 10.1101/051524 (published DOI: 10.1093/hmg/ddw160)

One way to design a drug is to attempt to phenocopy a genetic variant that is known to have the desired effect. In general, drugs that are supported by genetic associations progress further in the development pipeline. However, the number of associations that are candidates for development into drugs is limited because many associations are in noncoding regions or difficult to target genes. Approaches that overlay information from pathway databases or biological networks can expand the potential target list. In cases where the initial variant is not targetable or there is no variant with the desired effect, this may reveal new means to target a disease. In this review we discuss recent examples in the domain of pathway and network-based drug repositioning from genetic associations. We highlight important caveats and challenges for the field, and we discuss opportunities for further development.

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