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Article Dans Une Revue Environmental Health Perspectives Année : 2020

CoMPARA: Collaborative Modeling Project for Androgen Receptor Activity

Kamel Mansouri (1) , Nicole Kleinstreuer (2) , Ahmed Abdelaziz , Domenico Alberga (3) , Vinicius Alves (4, 5) , Patrik Andersson (6) , Carolina Andrade (4) , Fang Bai (7) , Ilya Balabin , Davide Ballabio (8) , Emilio Benfenati (9) , Barun Bhhatarai (10) , Scott Boyer (11) , Jingwen Chen (12) , Viviana Consonni (13) , Sherif Farag (14) , Denis Fourches (15) , Alfonso García-Sosa (16) , Paola Gramatica (10) , Francesca Grisoni (8) , Chris Grulke (17) , Huixiao Hong (18) , Dragos Horvath (19) , Xin Hu (20) , Ruili Huang (20) , Nina Jeliazkova , Jiazhong Li (7) , Xuehua Li (12) , Huanxiang Liu (7) , Serena Manganelli (21) , Giuseppe Mangiatordi (3) , Uko Maran (16) , Gilles Marcou (19) , Todd Martin , Eugene Muratov (14) , Dac-Trung Nguyen (20) , Orazio Nicolotti (3) , Nikolai Nikolov (22) , Ulf Norinder (11) , Ester Papa (10) , Michel Petitjean (23) , Geven Piir (24) , Pavel Pogodin (25) , Vladimir Poroikov (25) , Xianliang Qiao (12) , Ann Richard (1) , Alessandra Roncaglioni (21) , Patricia Ruiz (26) , Chetan Rupakheti (27) , Sugunadevi Sakkiah , Alessandro Sangion (10) , Karl-Werner Schramm , Chandrabose Selvaraj (18) , Imran Shah (1) , Sulev Sild (16) , Lixia Sun (28) , Olivier Taboureau (29) , Yun Tang (28) , Igor V. Tetko (30) , Roberto Todeschini (13) , Weida Tong (18) , Daniela Trisciuzzi (3) , Alexander Tropsha (31) , George van den Driessche (15) , Alexandre Varnek (19) , Zhongyu Wang (12) , Eva Wedebye (22) , Antony Williams (1) , Hongbin Xie (12) , Alexey Zakharov , Ziye Zheng (6) , Richard Judson (1)
1 EPA - US Environmental Protection Agency
2 National Institute of Environmental Health Sciences, National Institutes of Health
3 UNIBA - Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro
4 Federal University of Goiás [Jataí]
5 Dept. of Statistics - University of North Carolina - Chapel Hill
6 Umeå University
7 Lanzhou University
8 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
9 Istituto di Ricerche Farmacologiche "Mario Negri"
10 Uninsubria - Universitá degli Studi dell’Insubria = University of Insubria [Varese]
11 Karolinska Institutet [Stockholm]
12 Dalian University of Technology
13 Department of Statistics University of Milano Bicocca
14 UNC - University of North Carolina at Chapel Hill
15 NC State - North Carolina State University [Raleigh]
16 Institute of Computer Science [University of Tartu, Estonie]
17 U.S. ENVIRONMENTAL PROTECTION AGENCY USA
18 FDA - U.S. Food and Drug Administration
19 Laboratoire de Chémoinformatique
20 NIH - National Institutes of Health [Bethesda, MD, USA]
21 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
22 DTU - Danmarks Tekniske Universitet = Technical University of Denmark
23 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
24 University of Tartu
25 IBMC - Institute of Biomedical Chemistry [Moscou]
26 Centers for Disease Control and Prevention
27 The University of Chicago Medicine [Chicago]
28 East China University of Science and Technology
29 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
30 German Research Center for Environmental Health - Helmholtz Center München (GmbH)
31 UNC - University of North Carolina [Chapel Hill]
Ahmed Abdelaziz
  • Fonction : Auteur
Fang Bai
  • Fonction : Auteur
Ilya Balabin
  • Fonction : Auteur
Dragos Horvath
Nina Jeliazkova
  • Fonction : Auteur
Jiazhong Li
  • Fonction : Auteur
Huanxiang Liu
  • Fonction : Auteur
Gilles Marcou
Todd Martin
  • Fonction : Auteur
Ulf Norinder
  • Fonction : Auteur
  • PersonId : 992369
Geven Piir
  • Fonction : Auteur
Patricia Ruiz
  • Fonction : Auteur
  • PersonId : 867136
Sugunadevi Sakkiah
  • Fonction : Auteur
Karl-Werner Schramm
  • Fonction : Auteur
Alexandre Varnek
Antony Williams
Alexey Zakharov
  • Fonction : Auteur
Ziye Zheng
  • Fonction : Auteur

Résumé

BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling. OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP). METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCastTM metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCastTM/Tox21 HTS in vitro assays. RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set. DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of ~ 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.
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Dates et versions

hal-02489682 , version 1 (10-11-2020)

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Domaine public

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Kamel Mansouri, Nicole Kleinstreuer, Ahmed Abdelaziz, Domenico Alberga, Vinicius Alves, et al.. CoMPARA: Collaborative Modeling Project for Androgen Receptor Activity. Environmental Health Perspectives, 2020, 128 (2), pp.027002. ⟨10.1289/EHP5580⟩. ⟨hal-02489682⟩
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