The Tox21 10K Compound Library: Collaborative Chemistry Advancing Toxicology.
The Tox21 10K Compound Library: Collaborative Chemistry Advancing Toxicology.
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DOI：
10.1021/acs.chemrestox.0c00264
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发表时间：
2021-02-15
影响因子：
4.1
通讯作者：
Tice RR
中科院分区：
文献类型：
--
作者：
Richard AM;Huang R;Waidyanatha S;Shinn P;Collins BJ;Thillainadarajah I;Grulke CM;Williams AJ;Lougee RR;Judson RS;Houck KA;Shobair M;Yang C;Rathman JF;Yasgar A;Fitzpatrick SC;Simeonov A;Thomas RS;Crofton KM;Paules RS;Bucher JR;Austin CP;Kavlock RJ;Tice RR
Since 2009, the Tox21 project has screened ∼8500 chemicals in more than 70 high-throughput assays, generating upward of 100 million data points, with all data publicly available through partner websites at the United States Environmental Protection Agency (EPA), National Center for Advancing Translational Sciences (NCATS), and National Toxicology Program (NTP). Underpinning this public effort is the largest compound library ever constructed specifically for improving understanding of the chemical basis of toxicity across research and regulatory domains. Each Tox21 federal partner brought specialized resources and capabilities to the partnership, including three approximately equal-sized compound libraries. All Tox21 data generated to date have resulted from a confluence of ideas, technologies, and expertise used to design, screen, and analyze the Tox21 10K library. The different programmatic objectives of the partners led to three distinct, overlapping compound libraries that, when combined, not only covered a diversity of chemical structures, use-categories, and properties but also incorporated many types of compound replicates. The history of development of the Tox21 “10K” chemical library and data workflows implemented to ensure quality chemical annotations and allow for various reproducibility assessments are described. Cheminformatics profiling demonstrates how the three partner libraries complement one another to expand the reach of each individual library, as reflected in coverage of regulatory lists, predicted toxicity end points, and physicochemical properties. ToxPrint chemotypes (CTs) and enrichment approaches further demonstrate how the combined partner libraries amplify structure–activity patterns that would otherwise not be detected. Finally, CT enrichments are used to probe global patterns of activity in combined ToxCast and Tox21 activity data sets relative to test-set size and chemical versus biological end point diversity, illustrating the power of CT approaches to discern patterns in chemical–activity data sets. These results support a central premise of the Tox21 program: A collaborative merging of programmatically distinct compound libraries would yield greater rewards than could be achieved separately.
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影响因子：
7.4
作者：
Attene-Ramos, Matias S.;Miller, Nicole;Huang, Ruili;Michael, Sam;Itkin, Misha;Kavlock, Robert J.;Austin, Christopher P.;Shinn, Paul;Simeonov, Anton;Tice, Raymond R.;Xia, Menghang
通讯作者：
Xia, Menghang
影响因子：
--
作者：
Cassano A;Manganaro A;Martin T;Young D;Piclin N;Pintore M;Bigoni D;Benfenati E
通讯作者：
Benfenati E
影响因子：
4.6
作者：
Huang R;Sakamuru S;Martin MT;Reif DM;Judson RS;Houck KA;Casey W;Hsieh JH;Shockley KR;Ceger P;Fostel J;Witt KL;Tong W;Rotroff DM;Zhao T;Shinn P;Simeonov A;Dix DJ;Austin CP;Kavlock RJ;Tice RR;Xia M
通讯作者：
Xia M
影响因子：
10.4
作者：
Huang R;Xia M;Cho MH;Sakamuru S;Shinn P;Houck KA;Dix DJ;Judson RS;Witt KL;Kavlock RJ;Tice RR;Austin CP
通讯作者：
Austin CP
影响因子：
3
作者：
Arena, VC;Sussman, NB;Macina, OT
通讯作者：
Macina, OT