Extending the Small Molecule Similarity Principle to All Levels of Biology
87 Pages Posted: 30 Apr 2019 Sneak Peek Status: Review CompleteMore...
We present the Chemical Checker (CC), a resource that provides processed, harmonized and integrated bioactivity data on 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 profiles. 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, and 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.
Keywords: Bioactivity signatures, chemical space, compound similarity principle, systems pharmacology
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