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Determination of minimal transcriptional signatures of compounds for target prediction

Nigsch, Florian and Hutz, Janna and Cornett, Allen and Selinger, Douglas and Mcallister, Gregory and Bandyopadhyay, Somnath and Loureiro, Joseph and Jenkins, Jeremy (2012) Determination of minimal transcriptional signatures of compounds for target prediction. EURASIP Journal on Bioinformatics and Systems Biology, 1 (2). p. 2.

Abstract

The identification of molecular target and mechanism of action of compounds is a key hurdle in drug discovery. Multiplexed techniques for bead-based expression profiling allow the measurement of transcriptional signatures of compound-treated cells in high-throughput mode. Such profiles can be used to gain insight into compounds’ mode of action (MoA) and the protein targets they are modulating. Through the proxy of target prediction from such gene signatures we explored important aspects of the use of transcriptional profiles to capture biological variability of perturbed cellular assays. We found that signatures derived from expression data and signatures derived from biological interactions networks performed equally well, and we showed that gene signatures can be optimised using a genetic algorithm. Gene signatures of ~128 genes seemed to be most generic, capturing a maximum of the perturbation inflicted on cells through compound treatment. Moreover, we found evidence for oxidative phosphorylation to be one of the most general ways to capture compound perturbation.

Item Type: Article
Date Deposited: 26 Apr 2016 23:46
Last Modified: 26 Apr 2016 23:46
URI: https://oak.novartis.com/id/eprint/6673

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