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Public domain HTS fingerprints: design and evaluation of compound bioactivity profiles from PubChem’s bioassay repository

Helal, Kazi Yasin, Maciejewski, Mateusz , Gregori-Puigjane, Elisabet, Glick, Meir and Wassermann, Anne Mai (2016) Public domain HTS fingerprints: design and evaluation of compound bioactivity profiles from PubChem’s bioassay repository. Journal of Chemical Information and Modeling, 56 (2). pp. 390-398. ISSN 1549-95961549-960X


Molecular profiling efforts aim at characterizing the biological actions of small molecules by screening them in hundreds of different biochemical and/or cell-based assays. Together, these assays yield a rich data landscape of the target-based and phenotypic effects of the tested compounds. However, submitting an entire compound library to a molecular profiling panel can easily become cost-prohibitive. Here, we make use of historical screening assays to create comprehensive bioactivity profiles for more than 300,000 small molecules. These bioactivity profiles, termed PubChem high-throughput screening fingerprints (PubChem HTSFPs), report small molecule activities in 243 different PubChem bioassays. Although the assays originate from originally independently pursued drug or probe discovery projects, we demonstrate their value as molecular signatures when used in combination. We use these PubChem HTSFPs as molecular descriptors in hit expansion experiments for 33 different targets and phenotypes, showing that, on average, they lead to 29 times as many hits in a set of 1000 molecules chosen as a random screening subset of the same size (average ROC score: 0.85). Moreover, we demonstrate that PubChem HTSFPs retrieve hits that are structurally diverse and distinct from active compounds retrieved by chemical similarity-based hit expansion methods. PubChem HTSFPs are made freely available for the chemical biology research community and can be downloaded from the Novartis website.

Item Type: Article
Keywords: bioactivity profiles, HTS fingerprints, PubChem bioassays, scaffold hopping, virtual screening
Date Deposited: 08 Dec 2015 00:45
Last Modified: 04 Jul 2016 23:45


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