The Use of Large-Scale Chemically-Induced Transcriptome Data Acquired from LINCS to Study Small Molecules.

Abstract

Identification of the modes of action of bioactive compounds is an important issue in chemical systems biology. In this chapter we review a recently developed data-driven approach using large-scale chemically induced transcriptome data acquired from the Library of Integrated Network-based Cellular Signatures to elucidate the modes of action of bioactive compounds. First, we present a method for pathway enrichment analyses of regulated genes to reveal biological pathways activated by compounds. Next, we present a method using the pre-knowledge on chemical-protein interactome for predicting potential target proteins, including primary targets and off-targets, with transcriptional similarity. Finally, we present a method based on the target proteins for predicting new therapeutic indications for a variety of diseases. These approaches are expected to be useful for mode-of-action analysis, drug discovery, and drug repositioning.