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Extending the small molecule similarity principle to all levels of biology

Duran-Frigola, M.; Pauls, E.; Gitart-Pla, O.; Bertoni, M.; Alcalde, V.; Amat, D.; Juan-Blanco, T.; Aloy, P.

2019-08-24 bioinformatics
10.1101/745703 bioRxiv
Show abstract

We present the Chemical Checker (CC), a resource that provides processed, harmonized and integrated bioactivity data on 800,000 small molecules. The CC divides data into five levels of increasing complexity, ranging from the chemical properties of compounds to their clinical outcomes. In between, it considers targets, off-targets, perturbed biological networks and several cell-based assays such as gene expression, growth inhibition and morphological profilings. In the CC, bioactivity data are expressed in a vector format, which naturally extends the notion of chemical similarity between compounds to similarities between bioactivity signatures of different kinds. We show how CC signatures can boost the performance of drug discovery tasks that typically capitalize on chemical descriptors, including target identification and library characterization. Moreover, we demonstrate and experimentally validate that CC signatures can be used to reverse and mimic biological signatures of disease models and genetic perturbations, options that are otherwise impossible using chemical information alone.

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