Open PHACTS computational protocols for in silico target validation of cellular phenotypic screens: knowing the knowns.

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  • dc.contributor.author Digles, Danielaca
  • dc.contributor.author Queralt Rosinach, Núriaca
  • dc.contributor.author Furlong, Laura I., 1971-ca
  • dc.contributor.author Jacoby, Edgarca
  • dc.date.accessioned 2017-01-11T08:36:41Z
  • dc.date.available 2017-01-11T08:36:41Z
  • dc.date.issued 2016
  • dc.description.abstract Phenotypic screening is in a renaissance phase and is expected by many academic and industry leaders to accelerate the discovery of new drugs for new biology. Given that phenotypic screening is per definition target agnostic, the emphasis of in silico and in vitro follow-up work is on the exploration of possible molecular mechanisms and efficacy targets underlying the biological processes interrogated by the phenotypic screening experiments. Herein, we present six exemplar computational protocols for the interpretation of cellular phenotypic screens based on the integration of compound, target, pathway, and disease data established by the IMI Open PHACTS project. The protocols annotate phenotypic hit lists and allow follow-up experiments and mechanistic conclusions. The annotations included are from ChEMBL, ChEBI, GO, WikiPathways and DisGeNET. Also provided are protocols which select from the IUPHAR/BPS Guide to PHARMACOLOGY interaction file selective compounds to probe potential targets and a correlation robot which systematically aims to identify an overlap of active compounds in both the phenotypic as well as any kinase assay. The protocols are applied to a phenotypic pre-lamin A/C splicing assay selected from the ChEMBL database to illustrate the process. The computational protocols make use of the Open PHACTS API and data and are built within the Pipeline Pilot and KNIME workflow tools.ca
  • dc.description.sponsorship The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115191, resources of which are composed of financial contributions from the EU's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in-kind contribution. L. I. F. received support from ISCIII-FEDER (PI13/00082, CP10/00524) and the EU H2020 Programme 2014-2020 under grant agreements no. 634143 (MedBioinformatics) and no. 676559 (Elixir-Excelerate). The Research Programme on Biomedical Informatics (GRIB) is a node of the Spanish National Institute of Bioinformatics (INB).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Digles D, Zdrazil B, Neefs JM, Van Vlijmen H, Herhaus C, Caracoti A. et al. Open PHACTS computational protocols for in silico target validation of cellular phenotypic screens: knowing the knowns. Medchemcomm. 2016 Jun 1;7(6):1237-44. DOI: 10.1039/c6md00065gca
  • dc.identifier.doi http://dx.doi.org/10.1039/c6md00065g
  • dc.identifier.issn 2040-2503
  • dc.identifier.uri http://hdl.handle.net/10230/27868
  • dc.language.iso engca
  • dc.publisher Royal Society of Chemistryca
  • dc.relation.ispartof Medchemcomm. 2016 Jun 1;7(6):1237-44
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115191
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634143
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/676559
  • dc.rights This journal is © The Royal Society of Chemistry 2016. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri https://creativecommons.org/licenses/by/3.0/ca
  • dc.subject.other Fenotipca
  • dc.subject.other Biologia computacionalca
  • dc.title Open PHACTS computational protocols for in silico target validation of cellular phenotypic screens: knowing the knowns.ca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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