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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
Nature Communications, Volume 10, No. 1, Article 2674, Year 2019
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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. © 2019, The Author(s).
Authors & Co-Authors
Menden, Michael Patrick
United Kingdom, Cambridge
Astrazeneca
United Kingdom, Hinxton
European Molecular Biology Laboratory
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Wang, Dennis Y.Q.
United Kingdom, Cambridge
Astrazeneca
United Kingdom, Sheffield
The University of Sheffield
Mason, Michael J.
United States, Seattle
Sage Bionetworks
Szalai, Bence
Hungary, Budapest
Semmelweis Egyetem
Hungary, Budapest
Magyar Tudomanyos Akademia
Germany, Aachen
Rheinisch-westfälische Technische Hochschule Aachen
Bulusu, Krishna C.
United Kingdom, Cambridge
Astrazeneca
Guan, Yuanfang
United States, Ann Arbor
University of Michigan, Ann Arbor
Yu, Thomas V.
United States, Seattle
Sage Bionetworks
Kang, Jaewoo
South Korea, Seoul
Korea University
Jeon, Minji
South Korea, Seoul
Korea University
Wolfinger, Russell D.
United States, Cary
Sas Institute, Inc.
Nguyen, Tin C.
United States, Reno
University of Nevada, Reno
Zaslavskiy, Mikhail
Unknown Affiliation
Abante, Jordi
United States, College Station
Texas A&m University
Abecassis, Barbara Schmitz
Netherlands, Maastricht
Universiteit Maastricht
Aben, Nanne
Netherlands, Amsterdam
The Netherlands Cancer Institute
Netherlands, Delft
Delft University of Technology
Aghamirzaie, Delasa
United States, Blacksburg
Virginia Polytechnic Institute and State University
Aittokallio, Tero A.
Finland, Helsinki
Helsingin Yliopisto
Akhtari, Farida S.
United States, Raleigh
Nc State University
Al-Lazikani, Bissan
United Kingdom, London
The Institute of Cancer Research
Alam, Tanvir
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Allam, Amin
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Allen, Chad H.G.
United Kingdom, Cambridge
University of Cambridge
de Almeida, Mariana Pelicano
Netherlands, Maastricht
Universiteit Maastricht
Altarawy, Doaa
United States, Blacksburg
Virginia Polytechnic Institute and State University
Egypt, Alexandria
Alexandria University
Alves, Vinicius M.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Amadoz, Alicia
Unknown Affiliation
Anchang, Benedict
United States, Palo Alto
Stanford University
Antolín, Albert A.
United Kingdom, London
The Institute of Cancer Research
Ash, Jeremy R.
United States, Raleigh
Nc State University
Aznar, Victoria Romeo
Argentina, Buenos Aires
Leloir Institute Foundation
Ba-Alawi, Wail
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Bagheri, Moeen
Canada, Toronto
University of Toronto
Bajic, Vladimir B.
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Ball, Gordon
Sweden, Solna
Science for Life Laboratory
Ballester, Pedro J.
France, Marseille
Centre de Recherche en Cancérologie de Marseille
France, Marseille
Institut Paoli-calmettes
France, Marseille
Aix Marseille Université
Baptista, Delora
Portugal, Braga
Universidade do Minho
Bare, Christopher J.
United States, Seattle
Sage Bionetworks
Bateson, Mathilde
Unknown Affiliation
Bender, Andreas
United Kingdom, Cambridge
University of Cambridge
Bertrand, Denis
Singapore, Singapore City
A-star, Genome Institute of Singapore
Boroevich, Keith Anthony
Japan, Yokohama
Riken Center for Integrative Medical Sciences
Bosdriesz, Evert
Netherlands, Amsterdam
The Netherlands Cancer Institute
Bougouffa, Salim
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Bounova, Gergana
Netherlands, Amsterdam
The Netherlands Cancer Institute
Brouwer, Thomas
United Kingdom, Cambridge
University of Cambridge
Bryant, Barbara M.
Unknown Affiliation
Calaza, Manuel
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Calderone, Alberto
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Calza, S.
Italy, Brescia
Università Degli Studi Di Brescia
Sweden, Stockholm
Karolinska Institutet
Capuzzi, Stephen J.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Carbonell-Caballero, José
Spain, Barcelona
Barcelona Institute of Science and Technology Bist
Carlin, Daniel E.
United States, La Jolla
University of California, San Diego
Carter, Hannah E.
United States, La Jolla
University of California, San Diego
Castagnoli, Luisa
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Çelebi, Remzi
Turkey, Izmir
Ege Üniversitesi
Cesareni, Gianni
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Chang, Hyeokyoon
South Korea, Seoul
Korea University
Chen, Guocai
United States, Houston
University of Texas Health Science Center at Houston
Chen, Haoran
United States, College Station
Texas A&m University
Chen, Huiyuan
United States, Cleveland
Case Western Reserve University
Cheng, Lijun
United States, Indianapolis
Indiana University School of Medicine
Chernomoretz, Ariel
Argentina, Buenos Aires
Leloir Institute Foundation
Chicco, Davide
Canada, Toronto
Princess Margaret Cancer Centre
Cho, Kwang-hyun
South Korea, Daejeon
Korea Advanced Institute of Science and Technology
Choi, Daeseon
Unknown Affiliation
Choi, Jaejoon
Unknown Affiliation
Choi, Kwanghun
South Korea, Seoul
Korea University
Choi, Minsoo
Unknown Affiliation
De Cock, Martine
United States, Tacoma
University of Washington, Tacoma
Coker, Elizabeth A.
United Kingdom, London
The Institute of Cancer Research
Cortes-Ciriano, Isidro
France, Paris
Cnrs Centre National de la Recherche Scientifique
Cserzö, Miklós
Hungary, Budapest
Semmelweis Egyetem
Hungary, Budapest
Magyar Tudomanyos Akademia
Çubuk, Cankut
Spain, Sevilla
Hospital Universitario Virgen Del Rocío
Curtis, Christina N.
United States, Palo Alto
Stanford University
Daele, Dries Van
Belgium, Leuven
Ku Leuven
Dang, Cuong Cao
France, Marseille
Centre de Recherche en Cancérologie de Marseille
France, Marseille
Institut Paoli-calmettes
France, Marseille
Aix Marseille Université
Dijkstra, Tjeerd M.H.
Germany, Tubingen
Max Planck Institute for Developmental Biology
Dopazo, Joaquin A.
Spain, Sevilla
Hospital Universitario Virgen Del Rocío
Drəghici, Sorin
United States, Detroit
Wayne State University
Drosou, Anastasios
Greece, Thessaloniki
Centre for Research and Technology-hellas
Dumontier, Michel J.
Netherlands, Maastricht
Universiteit Maastricht
Ehrhart, Friederike
Netherlands, Maastricht
Universiteit Maastricht
Eid, Fatma Elzahraa
United States, Blacksburg
Virginia Polytechnic Institute and State University
Egypt, Cairo
Al-azhar University
ElHefnawi, Mahmoud M.
Egypt, Giza
National Research Centre
Egypt, 6th October
Nile University
Elmarakeby, Haitham A.
United States, Blacksburg
Virginia Polytechnic Institute and State University
Egypt, Cairo
Al-azhar University
van Engelen, Bo
Netherlands, Maastricht
Universiteit Maastricht
Engin, Hatice Billur
United States, La Jolla
University of California, San Diego
de Esch, Iwan J.P.
Netherlands, Amsterdam
Vrije Universiteit Amsterdam
Evelo, Chris T.A.
Netherlands, Maastricht
Universiteit Maastricht
Falcão, André O.
Portugal, Lisbon
Faculdade de Ciências, Universidade de Lisboa
Farag, Sherif
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Fernandez-Lozano, Carlos
Spain, A Coruna
Universidade da Coruña
Fisch, Kathleen M.
United States, La Jolla
University of California, San Diego
Flobak, Åsmund
Norway, Trondheim
Norges Teknisk-naturvitenskapelige Universitet
Norway, Trondheim
Universitetssykehuset I Trondheim
Fornari, Chiara
United Kingdom, Cambridge
Astrazeneca
Foroushani, Amir
United States, San Marcos
Texas State University
Fotso, Donatien Chedom
United Kingdom, Oxford
University of Oxford
Fourches, Denis
United States, Raleigh
Nc State University
Friend, Stephen H.
United States, Seattle
Sage Bionetworks
Frigessi, Arnoldo
Norway, Oslo
Universitetet I Oslo
Gao, Feng
Hong Kong, Hong Kong
City University of Hong Kong
Godzik, Adam
United States, San Diego
Sanford Burnham Prebys Medical Discovery Institute
Gomez-Cabrero, David
Sweden, Solna
Science for Life Laboratory
United Kingdom, London
King's College London
Gönen, Mehmet
Turkey, Istanbul
Koç Üniversitesi
Guney, Emre
Spain, Barcelona
Centro de Regulacion Genomica, Barcelona
Haibe-Kains, Benjamin
Canada, Toronto
University Health Network University of Toronto
Heath, Lenwood S.
United States, Blacksburg
Virginia Polytechnic Institute and State University
Hidalgo, Marta R.
Spain, Sevilla
Hospital Universitario Virgen Del Rocío
Hochreiter, Sepp
Austria, Linz
Johannes Kepler University Linz
Hu, Zhiyuan
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Huang, Rong Stephanie
United States, Minneapolis
University of Minnesota Twin Cities
Hunyady, László
Hungary, Budapest
Semmelweis Egyetem
Hungary, Budapest
Magyar Tudomanyos Akademia
Kanev, Georgi K.
Netherlands, Amsterdam
Vrije Universiteit Amsterdam
Kaski, Samuel
Finland, Espoo
Aalto University
Khamis, Abdullah M.
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Klambauer, Günter
Austria, Linz
Johannes Kepler University Linz
Knowles, David A.
United States, Palo Alto
Stanford University
Li, Lang
United States, Columbus
The Ohio State University College of Medicine
Lim, Weng Khong
Singapore, Singapore City
National University of Singapore
Lysenko, Artem
Japan, Yokohama
Riken Center for Integrative Medical Sciences
Marchal, Kathleen
Belgium, Ghent
Universiteit Gent
Marttinen, Pekka
Finland, Helsinki
Helsinki Institute for Information Technology
Michaut, Magali
Netherlands, Amsterdam
The Netherlands Cancer Institute
Módos, Dezső
United Kingdom, Cambridge
University of Cambridge
Motsinger-Reif, Alison Anne
United States, Raleigh
Nc State University
Mushthofa, Mushthofa
Belgium, Ghent
Universiteit Gent
Nagarajan, Niranjan
Singapore, Singapore City
A-star, Genome Institute of Singapore
Pawitan, Yudi
Sweden, Stockholm
Karolinska Institutet
Peng, Jian
United States, Urbana
University of Illinois Urbana-champaign
Pujana, Miguel Àngel G.
Spain, Hospitalet de Llobregat
Institute Catala Oncologia
Spain, Hospitalet de Llobregat
Institut D'investigació Biomedica de Bellvitge
Reyal, Fabien
France, Paris
Institut Curie
Richardson, Sylvia T.
United Kingdom, Cambridge
Mrc Biostatistics Unit
Shang, Mingmei
Sweden, Solna
Science for Life Laboratory
Shkedy, Ziv
Belgium, Hasselt
Universiteit Hasselt
Soufan, Othman Mohammad
Netherlands, Amsterdam
The Netherlands Cancer Institute
Tegnér, Jesper N.
Sweden, Solna
Science for Life Laboratory
Saudi Arabia, Thuwal
King Abdullah University of Science and Technology
Madani Tonekaboni, Seyed Ali
Canada, Toronto
University Health Network University of Toronto
Tsunoda, Tatsuhiko
Japan, Yokohama
Riken Center for Integrative Medical Sciences
Japan, Tokyo
Tokyo Medical and Dental University
Japan, Kawaguchi
Japan Science and Technology Agency
Verbeke, Lieven P.C.
Belgium, Ghent
Universiteit Gent
Wang, Xin
Hong Kong, Hong Kong
City University of Hong Kong
Wernisch, Lorenz
United Kingdom, Cambridge
Mrc Biostatistics Unit
White, Simon R.
United Kingdom, Cambridge
Mrc Biostatistics Unit
Willighagen, Egon L.
Netherlands, Maastricht
Universiteit Maastricht
Würdinger, Thomas W.
Netherlands, Amsterdam
Cancer Center Amsterdam
Yadav, Bhagwan
Finland, Helsinki
Helsingin Yliopisto
Yau, Christopher
United Kingdom, Birmingham
University of Birmingham
Zakharov, Alexey V.
United States, Bethesda
National Institutes of Health Nih
Zhao, Hongyu
United States, New Haven
Yale University
Ahsen, Mehmet Eren
United States, Yorktown Heights
Ibm Thomas J. Watson Research Center
Chaibub Neto, Elias
United States, Seattle
Sage Bionetworks
Norman, Thea C.
United States, Seattle
Sage Bionetworks
Stolovitzky, Gustavo A.
United States, Yorktown Heights
Ibm Thomas J. Watson Research Center
United States, New York
Icahn School of Medicine at Mount Sinai
Guinney, Justin H.
United States, Seattle
Sage Bionetworks
Sáez-Rodríguez, Julio
United Kingdom, Hinxton
European Molecular Biology Laboratory
Germany, Aachen
Rheinisch-westfälische Technische Hochschule Aachen
Germany, Heidelberg
Universität Heidelberg
Statistics
Citations: 219
Authors: 154
Affiliations: 133
Identifiers
Doi:
10.1038/s41467-019-09799-2
ISSN:
20411723
Research Areas
Cancer
Health System And Policy
Study Design
Case-Control Study