[Development of Decomposition Approach for Comprehensive Understanding of Drug Effects].

ABSTRACT

As the term polypharmacology suggests, there are multiple actions of small-molecule compounds. We proposed a decomposition and understanding concept that sheds light on the small effects in comparison to the large effects by decomposing these multiple effects. This concept was embodied by describing the effects of the compounds in a transcriptome profile, followed by factor analysis to extract latent variables as decomposed effects. Application of this approach to public datasets resulted in the inferences of compound effects consistent with existing knowledge such as gene ontologies and pathways. In one experimental validation, the potential inducibility of endoplasmic reticulum stress of several commercial drugs was detected by decomposition. Another study successfully discriminated the effects of a natural product and its derivatives despite their structural similarity. In the era of big data, it is important to infer conceptual elements composed of measurable elements as a higher layer than the given data of a specimen, which can expand our perception and understanding of the specimen. This review introduces an example of such a philosophy by applying it to the multiple effects of drugs to contribute to the understanding.