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Extending the Small Molecule Similarity Principle to All Levels of Biology

87 Pages Posted: 30 Apr 2019 Sneak Peek Status: Review Complete

See all articles by Miquel Duran-Frigola

Miquel Duran-Frigola

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Eduardo Pauls

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Oriol Guitart-Pla

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Martino Bertoni

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Modesto Orozco-Ruiz

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Víctor Alcalde

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Víctor M. Diaz

Autonomous University of Barcelona - Programa de Recerca en Càncer

Antoni Berenguer-Llergo

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

David Amat

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Teresa Juan-Blanco

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Antonio García de Herreros

Autonomous University of Barcelona - Programa de Recerca en Càncer

Patrick Aloy

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

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Abstract

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

Suggested Citation

Duran-Frigola, Miquel and Pauls, Eduardo and Guitart-Pla, Oriol and Bertoni, Martino and Orozco-Ruiz, Modesto and Alcalde, Víctor and Diaz, Víctor M. and Berenguer-Llergo, Antoni and Amat, David and Juan-Blanco, Teresa and de Herreros, Antonio García and Aloy, Patrick, Extending the Small Molecule Similarity Principle to All Levels of Biology (April 29, 2019). Available at SSRN: https://ssrn.com/abstract=3380254 or http://dx.doi.org/10.2139/ssrn.3380254
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Miquel Duran-Frigola

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology ( email )

Spain

Eduardo Pauls

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

Oriol Guitart-Pla

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

Martino Bertoni

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

Modesto Orozco-Ruiz

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

Víctor Alcalde

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

Víctor M. Diaz

Autonomous University of Barcelona - Programa de Recerca en Càncer

Spain

Antoni Berenguer-Llergo

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

David Amat

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

Teresa Juan-Blanco

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology

Spain

Antonio García De Herreros

Autonomous University of Barcelona - Programa de Recerca en Càncer

Spain

Patrick Aloy (Contact Author)

Barcelona Institute of Science and Technology (BIST) - Joint IRB-BSC-CRG Program in Computational Biology ( email )

Spain

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