دورية أكاديمية
Connecting Small Molecules with Similar Assay Performance Profiles Leads to New Biological Hypotheses.
| العنوان: | Connecting Small Molecules with Similar Assay Performance Profiles Leads to New Biological Hypotheses. |
|---|---|
| المؤلفون: | Dančík V; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA Mathematical Institute of the Slovak Academy of Sciences, Košice, Slovakia (on leave)., Carrel H; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Bodycombe NE; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Seiler KP; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA Champlain College, Division of Information Technology & Sciences, Burlington, VT, USA., Fomina-Yadlin D; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Kubicek ST; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA CeMM Research Center for Molecular Medicine, Vienna, Austria., Hartwell K; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Shamji AF; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Wagner BK; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA., Clemons PA; Center for the Science of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, USA pclemons@broadinstitute.org. |
| المصدر: | Journal of biomolecular screening [J Biomol Screen] 2014 Jun; Vol. 19 (5), pp. 771-81. Date of Electronic Publication: 2014 Jan 24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Sage Publications Country of Publication: United States NLM ID: 9612112 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-454X (Electronic) Linking ISSN: 10870571 NLM ISO Abbreviation: J Biomol Screen Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2004- > : Thousand Oaks, CA : Sage Publications Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c1996- |
| مواضيع طبية MeSH: | Drug Evaluation, Preclinical/*methods , High-Throughput Screening Assays/*methods , Small Molecule Libraries/*chemistry, Algorithms ; Animals ; Bayes Theorem ; Cell Line, Tumor ; Cluster Analysis ; Humans ; Membrane Potential, Mitochondrial ; Mice ; Models, Molecular ; Phenotype ; Reproducibility of Results |
| مستخلص: | High-throughput screening allows rapid identification of new candidate compounds for biological probe or drug development. Here, we describe a principled method to generate "assay performance profiles" for individual compounds that can serve as a basis for similarity searches and cluster analyses. Our method overcomes three challenges associated with generating robust assay performance profiles: (1) we transform data, allowing us to build profiles from assays having diverse dynamic ranges and variability; (2) we apply appropriate mathematical principles to handle missing data; and (3) we mitigate the fact that loss-of-signal assay measurements may not distinguish between multiple mechanisms that can lead to certain phenotypes (e.g., cell death). Our method connected compounds with similar mechanisms of action, enabling prediction of new targets and mechanisms both for known bioactives and for compounds emerging from new screens. Furthermore, we used Bayesian modeling of promiscuous compounds to distinguish between broadly bioactive and narrowly bioactive compound communities. Several examples illustrate the utility of our method to support mechanism-of-action studies in probe development and target identification projects. (© 2014 Society for Laboratory Automation and Screening.) |
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| معلومات مُعتمدة: | UL1RR024924 United States RR NCRR NIH HHS; RL1HG004671 United States HG NHGRI NIH HHS; DP2 DK083048 United States DK NIDDK NIH HHS; UL1 RR024924 United States RR NCRR NIH HHS; RL1 GM084437 United States GM NIGMS NIH HHS; DP2-DK083048 United States DK NIDDK NIH HHS; RL1 HG004671 United States HG NHGRI NIH HHS; RL1 CA133834 United States CA NCI NIH HHS; RL1CA133834 United States CA NCI NIH HHS; RL1GM084437 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: high-throughput screening; mechanism of action; small-molecule profiling; target identification |
| المشرفين على المادة: | 0 (Small Molecule Libraries) |
| تواريخ الأحداث: | Date Created: 20140128 Date Completed: 20161213 Latest Revision: 20211021 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5554958 |
| DOI: | 10.1177/1087057113520226 |
| PMID: | 24464433 |
| قاعدة البيانات: | MEDLINE |
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