Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Autores
Menden, Michael P.; Wang, Dennis; Mason, Mike J.; Szalai, Bence; Bulusu, Krishna C.; Guan, Yuanfang; Yu, Thomas; Kang, Jaewoo; Jeon, Minji; Wolfinger, Russ; Nguyen, Tin; Zaslavskiy, Mikhail; Chernomoretz, Ariel; Jang, In Sock; Ghazoui, Zara; Ahsen, Mehmet Eren; Vogel, Robert; Neto, Elias Chaibub; Norman, Thea; Tang, Eric K. Y.; Garnett, Mathew J.; Di Veroli, Giovanni Y.; Fawell, Stephen; Stolovitzky, Gustavo; Guinney, Justin; Dry, Jonathan R.; Saez-Rodriguez, Julio
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
Fil: Menden, Michael P.. Helmholtz Zentrum München - German Research Center for Environmental Health. Institute of Computational Biology; Alemania. AstraZeneca; Reino Unido. European Molecular Biology Laboratory; Reino Unido
Fil: Wang, Dennis. AstraZeneca; Reino Unido. University of Sheffield; Reino Unido
Fil: Mason, Mike J.. Sage Bionetworks; Estados Unidos
Fil: Szalai, Bence. Semmelweis University; Hungría. RWTH Aachen University; Alemania
Fil: Bulusu, Krishna C.. Astrazeneca; Reino Unido
Fil: Guan, Yuanfang. University of Michigan; Estados Unidos
Fil: Yu, Thomas. Sage Bionetworks; Estados Unidos
Fil: Kang, Jaewoo. Korea University; Corea del Norte
Fil: Jeon, Minji. Korea University; Corea del Norte
Fil: Wolfinger, Russ. Sas Institute, Inc.; Estados Unidos
Fil: Nguyen, Tin. University of Nevada; Estados Unidos
Fil: Zaslavskiy, Mikhail. Owkin, Inc.; Estados Unidos
Fil: Chernomoretz, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Jang, In Sock. Sage Bionetworks; Estados Unidos
Fil: Ghazoui, Zara. AstraZeneca; Reino Unido
Fil: Ahsen, Mehmet Eren. IBM Research. Thomas J. Watson Research Center; Estados Unidos
Fil: Vogel, Robert. IBM Research. Thomas J. Watson Research Center; Estados Unidos
Fil: Neto, Elias Chaibub. Sage Bionetworks; Estados Unidos
Fil: Norman, Thea. Sage Bionetworks; Estados Unidos
Fil: Tang, Eric K. Y.. AstraZeneca; Reino Unido
Fil: Garnett, Mathew J.. Wellcome Sanger Institute; Reino Unido
Fil: Di Veroli, Giovanni Y.. AstraZeneca; Reino Unido
Fil: Fawell, Stephen. AstraZeneca; Reino Unido
Fil: Stolovitzky, Gustavo. IBM Research. Thomas J. Watson Research Center; Estados Unidos. Icahn School of Medicine at Mount Sinai; Estados Unidos
Fil: Guinney, Justin. Sage Bionetworks; Estados Unidos
Fil: Dry, Jonathan R.. AstraZeneca; Reino Unido
Fil: Saez-Rodriguez, Julio. European Molecular Biology Laboratory; Reino Unido. RWTH Aachen University; Alemania
Materia
Drug synergy
Biomarkers
Cancer treatment
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/148271

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network_name_str CONICET Digital (CONICET)
spelling Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screenMenden, Michael P.Wang, DennisMason, Mike J.Szalai, BenceBulusu, Krishna C.Guan, YuanfangYu, ThomasKang, JaewooJeon, MinjiWolfinger, RussNguyen, TinZaslavskiy, MikhailChernomoretz, ArielJang, In SockGhazoui, ZaraAhsen, Mehmet ErenVogel, RobertNeto, Elias ChaibubNorman, TheaTang, Eric K. Y.Garnett, Mathew J.Di Veroli, Giovanni Y.Fawell, StephenStolovitzky, GustavoGuinney, JustinDry, Jonathan R.Saez-Rodriguez, JulioDrug synergyBiomarkersCancer treatmenthttps://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Fil: Menden, Michael P.. Helmholtz Zentrum München - German Research Center for Environmental Health. Institute of Computational Biology; Alemania. AstraZeneca; Reino Unido. European Molecular Biology Laboratory; Reino UnidoFil: Wang, Dennis. AstraZeneca; Reino Unido. University of Sheffield; Reino UnidoFil: Mason, Mike J.. Sage Bionetworks; Estados UnidosFil: Szalai, Bence. Semmelweis University; Hungría. RWTH Aachen University; AlemaniaFil: Bulusu, Krishna C.. Astrazeneca; Reino UnidoFil: Guan, Yuanfang. University of Michigan; Estados UnidosFil: Yu, Thomas. Sage Bionetworks; Estados UnidosFil: Kang, Jaewoo. Korea University; Corea del NorteFil: Jeon, Minji. Korea University; Corea del NorteFil: Wolfinger, Russ. Sas Institute, Inc.; Estados UnidosFil: Nguyen, Tin. University of Nevada; Estados UnidosFil: Zaslavskiy, Mikhail. Owkin, Inc.; Estados UnidosFil: Chernomoretz, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Jang, In Sock. Sage Bionetworks; Estados UnidosFil: Ghazoui, Zara. AstraZeneca; Reino UnidoFil: Ahsen, Mehmet Eren. IBM Research. Thomas J. Watson Research Center; Estados UnidosFil: Vogel, Robert. IBM Research. Thomas J. Watson Research Center; Estados UnidosFil: Neto, Elias Chaibub. Sage Bionetworks; Estados UnidosFil: Norman, Thea. Sage Bionetworks; Estados UnidosFil: Tang, Eric K. Y.. AstraZeneca; Reino UnidoFil: Garnett, Mathew J.. Wellcome Sanger Institute; Reino UnidoFil: Di Veroli, Giovanni Y.. AstraZeneca; Reino UnidoFil: Fawell, Stephen. AstraZeneca; Reino UnidoFil: Stolovitzky, Gustavo. IBM Research. Thomas J. Watson Research Center; Estados Unidos. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Guinney, Justin. Sage Bionetworks; Estados UnidosFil: Dry, Jonathan R.. AstraZeneca; Reino UnidoFil: Saez-Rodriguez, Julio. European Molecular Biology Laboratory; Reino Unido. RWTH Aachen University; AlemaniaNature Publishing Group2019-06-17info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/148271Menden, Michael P.; Wang, Dennis; Mason, Mike J.; Szalai, Bence; Bulusu, Krishna C.; et al.; Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen; Nature Publishing Group; Nature Communications; 10; 1; 17-6-2019; 1-172041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-019-09799-2info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-019-09799-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:07Zoai:ri.conicet.gov.ar:11336/148271instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:51:07.471CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
title Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
spellingShingle Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
Menden, Michael P.
Drug synergy
Biomarkers
Cancer treatment
title_short Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
title_full Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
title_fullStr Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
title_full_unstemmed Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
title_sort Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
dc.creator.none.fl_str_mv Menden, Michael P.
Wang, Dennis
Mason, Mike J.
Szalai, Bence
Bulusu, Krishna C.
Guan, Yuanfang
Yu, Thomas
Kang, Jaewoo
Jeon, Minji
Wolfinger, Russ
Nguyen, Tin
Zaslavskiy, Mikhail
Chernomoretz, Ariel
Jang, In Sock
Ghazoui, Zara
Ahsen, Mehmet Eren
Vogel, Robert
Neto, Elias Chaibub
Norman, Thea
Tang, Eric K. Y.
Garnett, Mathew J.
Di Veroli, Giovanni Y.
Fawell, Stephen
Stolovitzky, Gustavo
Guinney, Justin
Dry, Jonathan R.
Saez-Rodriguez, Julio
author Menden, Michael P.
author_facet Menden, Michael P.
Wang, Dennis
Mason, Mike J.
Szalai, Bence
Bulusu, Krishna C.
Guan, Yuanfang
Yu, Thomas
Kang, Jaewoo
Jeon, Minji
Wolfinger, Russ
Nguyen, Tin
Zaslavskiy, Mikhail
Chernomoretz, Ariel
Jang, In Sock
Ghazoui, Zara
Ahsen, Mehmet Eren
Vogel, Robert
Neto, Elias Chaibub
Norman, Thea
Tang, Eric K. Y.
Garnett, Mathew J.
Di Veroli, Giovanni Y.
Fawell, Stephen
Stolovitzky, Gustavo
Guinney, Justin
Dry, Jonathan R.
Saez-Rodriguez, Julio
author_role author
author2 Wang, Dennis
Mason, Mike J.
Szalai, Bence
Bulusu, Krishna C.
Guan, Yuanfang
Yu, Thomas
Kang, Jaewoo
Jeon, Minji
Wolfinger, Russ
Nguyen, Tin
Zaslavskiy, Mikhail
Chernomoretz, Ariel
Jang, In Sock
Ghazoui, Zara
Ahsen, Mehmet Eren
Vogel, Robert
Neto, Elias Chaibub
Norman, Thea
Tang, Eric K. Y.
Garnett, Mathew J.
Di Veroli, Giovanni Y.
Fawell, Stephen
Stolovitzky, Gustavo
Guinney, Justin
Dry, Jonathan R.
Saez-Rodriguez, Julio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Drug synergy
Biomarkers
Cancer treatment
topic Drug synergy
Biomarkers
Cancer treatment
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
Fil: Menden, Michael P.. Helmholtz Zentrum München - German Research Center for Environmental Health. Institute of Computational Biology; Alemania. AstraZeneca; Reino Unido. European Molecular Biology Laboratory; Reino Unido
Fil: Wang, Dennis. AstraZeneca; Reino Unido. University of Sheffield; Reino Unido
Fil: Mason, Mike J.. Sage Bionetworks; Estados Unidos
Fil: Szalai, Bence. Semmelweis University; Hungría. RWTH Aachen University; Alemania
Fil: Bulusu, Krishna C.. Astrazeneca; Reino Unido
Fil: Guan, Yuanfang. University of Michigan; Estados Unidos
Fil: Yu, Thomas. Sage Bionetworks; Estados Unidos
Fil: Kang, Jaewoo. Korea University; Corea del Norte
Fil: Jeon, Minji. Korea University; Corea del Norte
Fil: Wolfinger, Russ. Sas Institute, Inc.; Estados Unidos
Fil: Nguyen, Tin. University of Nevada; Estados Unidos
Fil: Zaslavskiy, Mikhail. Owkin, Inc.; Estados Unidos
Fil: Chernomoretz, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Jang, In Sock. Sage Bionetworks; Estados Unidos
Fil: Ghazoui, Zara. AstraZeneca; Reino Unido
Fil: Ahsen, Mehmet Eren. IBM Research. Thomas J. Watson Research Center; Estados Unidos
Fil: Vogel, Robert. IBM Research. Thomas J. Watson Research Center; Estados Unidos
Fil: Neto, Elias Chaibub. Sage Bionetworks; Estados Unidos
Fil: Norman, Thea. Sage Bionetworks; Estados Unidos
Fil: Tang, Eric K. Y.. AstraZeneca; Reino Unido
Fil: Garnett, Mathew J.. Wellcome Sanger Institute; Reino Unido
Fil: Di Veroli, Giovanni Y.. AstraZeneca; Reino Unido
Fil: Fawell, Stephen. AstraZeneca; Reino Unido
Fil: Stolovitzky, Gustavo. IBM Research. Thomas J. Watson Research Center; Estados Unidos. Icahn School of Medicine at Mount Sinai; Estados Unidos
Fil: Guinney, Justin. Sage Bionetworks; Estados Unidos
Fil: Dry, Jonathan R.. AstraZeneca; Reino Unido
Fil: Saez-Rodriguez, Julio. European Molecular Biology Laboratory; Reino Unido. RWTH Aachen University; Alemania
description The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
publishDate 2019
dc.date.none.fl_str_mv 2019-06-17
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/148271
Menden, Michael P.; Wang, Dennis; Mason, Mike J.; Szalai, Bence; Bulusu, Krishna C.; et al.; Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen; Nature Publishing Group; Nature Communications; 10; 1; 17-6-2019; 1-17
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/148271
identifier_str_mv Menden, Michael P.; Wang, Dennis; Mason, Mike J.; Szalai, Bence; Bulusu, Krishna C.; et al.; Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen; Nature Publishing Group; Nature Communications; 10; 1; 17-6-2019; 1-17
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-019-09799-2
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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