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

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dc.contributor.authorMenden, Michael P.en
dc.contributor.authorWang, Dennisen
dc.contributor.authorMason, Mike J.en
dc.contributor.authorSzalai, Benceen
dc.contributor.authorBulusu, Krishna C.en
dc.contributor.authorGuan, Yuanfangen
dc.contributor.authorYu, Thomasen
dc.contributor.authorKang, Jaewooen
dc.contributor.authorJeon, Minjien
dc.contributor.authorWolfinger, Russen
dc.contributor.authorNguyen, Tinen
dc.contributor.authorZaslavskiy, Mikhailen
dc.contributor.authorJang, In Socken
dc.contributor.authorGhazoui, Zaraen
dc.contributor.authorAhsen, Mehmet Erenen
dc.contributor.authorVogel, Roberten
dc.contributor.authorNeto, Elias Chaibuben
dc.contributor.authorNorman, Theaen
dc.contributor.authorTang, Eric K. Y.en
dc.contributor.authorGarnett, Mathew J.en
dc.contributor.authorDi Veroli, Giovanni Y.en
dc.contributor.authorFawell, Stephenen
dc.contributor.authorStolovitzky, Gustavoen
dc.contributor.authorGuinney, Justinen
dc.contributor.authorDry, Jonathan R.en
dc.contributor.authorSaez-Rodriguez, Julioen
dc.contributor.authorAbante, Jordien
dc.contributor.authorAbecassis, Barbara Schmitzen
dc.contributor.authorAben, Nanneen
dc.contributor.authorAghamirzaie, Delasaen
dc.contributor.authorAittokallio, Teroen
dc.contributor.authorAkhtari, Farida S.en
dc.contributor.authorAl-lazikani, Bissanen
dc.contributor.authorAlam, Tanviren
dc.contributor.authorAllam, Aminen
dc.contributor.authorAllen, Chaden
dc.contributor.authorde Almeida, Mariana Pelicanoen
dc.contributor.authorAltarawy, Doaaen
dc.contributor.authorAlves, Viniciusen
dc.contributor.authorAmadoz, Aliciaen
dc.contributor.authorAnchang, Benedicten
dc.contributor.authorAntolin, Albert A.en
dc.contributor.authorAsh, Jeremy R.en
dc.contributor.authorRomeo Aznar, Victoriaen
dc.contributor.authorBa-alawi, Wailen
dc.contributor.authorBagheri, Moeenen
dc.contributor.authorBajic, Vladimiren
dc.contributor.authorBall, Gordonen
dc.contributor.authorBallester, Pedro J.en
dc.contributor.authorBaptista, Deloraen
dc.contributor.authorBare, Christopheren
dc.contributor.authorBateson, Mathildeen
dc.contributor.authorBender, Andreasen
dc.contributor.authorBertrand, Denisen
dc.contributor.authorWijayawardena, Bhagyaen
dc.contributor.authorBoroevich, Keith A.en
dc.contributor.authorBosdriesz, Everten
dc.contributor.authorBougouffa, Salimen
dc.contributor.authorBounova, Gerganaen
dc.contributor.authorBrouwer, Thomasen
dc.contributor.authorBryant, Barbaraen
dc.contributor.authorCalaza, Manuelen
dc.contributor.authorCalderone, Albertoen
dc.contributor.authorCalza, Stefanoen
dc.contributor.authorCapuzzi, Stephenen
dc.contributor.authorCarbonell-Caballero, Joseen
dc.contributor.authorCarlin, Danielen
dc.contributor.authorCarter, Hannahen
dc.contributor.authorCastagnoli, Luisaen
dc.contributor.authorCelebi, Remzien
dc.contributor.authorCesareni, Giannien
dc.contributor.authorChang, Hyeokyoonen
dc.contributor.authorChen, Guocaien
dc.contributor.authorChen, Haoranen
dc.contributor.authorChen, Huiyuanen
dc.contributor.authorCheng, Lijunen
dc.contributor.authorChernomoretz, Arielen
dc.contributor.authorChicco, Davideen
dc.contributor.authorCho, Kwang-Hyunen
dc.contributor.authorCho, Sunghwanen
dc.contributor.authorChoi, Daeseonen
dc.contributor.authorChoi, Jaejoonen
dc.contributor.authorChoi, Kwanghunen
dc.contributor.authorChoi, Minsooen
dc.contributor.authorDe Cock, Martineen
dc.contributor.authorCoker, Elizabethen
dc.contributor.authorCortes-Ciriano, Isidroen
dc.contributor.authorCserzo, Miklosen
dc.contributor.authorCubuk, Cankuten
dc.contributor.authorCurtis, Christinaen
dc.contributor.authorVan Daele, Driesen
dc.contributor.authorDang, Cuong C.en
dc.contributor.authorDijkstra, Tjeerden
dc.contributor.authorDopazo, Joaquinen
dc.contributor.authorDraghici, Sorinen
dc.contributor.authorDrosou, Anastasiosen
dc.contributor.authorDumontier, Michelen
dc.contributor.authorEhrhart, Friederikeen
dc.contributor.authorEid, Fatma-Elzahraaen
dc.contributor.authorElHefnawi, Mahmouden
dc.contributor.authorElmarakeby, Haitham A.en
dc.contributor.authorvan Engelen, Boen
dc.contributor.authorEngin, Hatice Billuren
dc.contributor.authorde Esch, Iwanen
dc.contributor.authorEvelo, Chrisen
dc.contributor.authorFalcao, Andre O.en
dc.contributor.authorFarag, Sherifen
dc.contributor.authorFernandez-Lozano, Carlosen
dc.contributor.authorFisch, Kathleenen
dc.contributor.authorFlobak, Asmunden
dc.contributor.authorFornari, Chiaraen
dc.contributor.authorForoushani, Amir B. K.en
dc.contributor.authorFotso, Donatien Chedomen
dc.contributor.authorFourches, Denisen
dc.contributor.authorFriend, Stephenen
dc.contributor.authorFrigessi, Arnoldoen
dc.contributor.authorGao, Fengen
dc.contributor.authorGao, Xiaotingen
dc.contributor.authorGerold, Jeffrey M.en
dc.contributor.authorGestraud, Pierreen
dc.contributor.authorGhosh, Samiken
dc.contributor.authorGillberg, Jussien
dc.contributor.authorGodoy-Lorite, Antoniaen
dc.contributor.authorGodynyuk, Lizzyen
dc.contributor.authorGodzik, Adamen
dc.contributor.authorGoldenberg, Annaen
dc.contributor.authorGomez-Cabrero, Daviden
dc.contributor.authorGonen, Mehmeten
dc.contributor.authorde Graaf, Chrisen
dc.contributor.authorGray, Harryen
dc.contributor.authorGrechkin, Maximen
dc.contributor.authorGuimera, Rogeren
dc.contributor.authorGuney, Emreen
dc.contributor.authorHaibe-Kains, Benjaminen
dc.contributor.authorHan, Younghyunen
dc.contributor.authorHase, Takeshien
dc.contributor.authorHe, Dien
dc.contributor.authorHe, Liyeen
dc.contributor.authorHeath, Lenwood S.en
dc.contributor.authorHellton, Kristoffer H.en
dc.contributor.authorHelmer-Citterich, Manuelaen
dc.contributor.authorHidalgo, Marta R.en
dc.contributor.authorHidru, Danielen
dc.contributor.authorHill, Steven M.en
dc.contributor.authorHochreiter, Seppen
dc.contributor.authorHong, Seungpyoen
dc.contributor.authorHovig, Eivinden
dc.contributor.authorHsueh, Ya-Chihen
dc.contributor.authorHu, Zhiyuanen
dc.contributor.authorHuang, Justin K.en
dc.contributor.authorHuang, R. Stephanieen
dc.contributor.authorHunyady, Laszloen
dc.contributor.authorHwang, Jinseuben
dc.contributor.authorHwang, Tae Hyunen
dc.contributor.authorHwang, Woochangen
dc.contributor.authorHwang, Yongdeuken
dc.contributor.authorIsayev, Olexandren
dc.contributor.authorWalk, Oliver Bear Don'ten
dc.contributor.authorJack, Johnen
dc.contributor.authorJahandideh, Samaden
dc.contributor.authorJi, Jiadongen
dc.contributor.authorJo, Yousangen
dc.contributor.authorKamola, Piotr J.en
dc.contributor.authorKanev, Georgi K.en
dc.contributor.authorKaracosta, Loukiaen
dc.contributor.authorKarimi, Mostafaen
dc.contributor.authorKaski, Samuelen
dc.contributor.authorKazanov, Maraten
dc.contributor.authorKhamis, Abdullah M.en
dc.contributor.authorKhan, Suleiman Alien
dc.contributor.authorKiani, Narsis A.en
dc.contributor.authorKim, Allenen
dc.contributor.authorKim, Jinhanen
dc.contributor.authorKim, Juntaeen
dc.contributor.authorKim, Kiseongen
dc.contributor.authorKim, Kyungen
dc.contributor.authorKim, Sunkyuen
dc.contributor.authorKim, Yongsooen
dc.contributor.authorKim, Yunseongen
dc.contributor.authorKirk, Paul D. W.en
dc.contributor.authorKitano, Hiroakien
dc.contributor.authorKlambauer, Gunteren
dc.contributor.authorKnowles, Daviden
dc.contributor.authorKo, Melissaen
dc.contributor.authorKohn-Luque, Alvaroen
dc.contributor.authorKooistra, Albert J.en
dc.contributor.authorKuenemann, Melaine A.en
dc.contributor.authorKuiper, Martinen
dc.contributor.authorKurz, Christophen
dc.contributor.authorKwon, Mijinen
dc.contributor.authorvan Laarhoven, Twanen
dc.contributor.authorLaegreid, Astriden
dc.contributor.authorLederer, Simoneen
dc.contributor.authorLee, Heewonen
dc.contributor.authorLee, Jeonen
dc.contributor.authorLee, Yun Wooen
dc.contributor.authorLeppaho, Eemelien
dc.contributor.authorLewis, Richarden
dc.contributor.authorLi, Jingen
dc.contributor.authorLi, Langen
dc.contributor.authorLiley, Jamesen
dc.contributor.authorLim, Weng Khongen
dc.contributor.authorLin, Chiehen
dc.contributor.authorLiu, Yiyien
dc.contributor.authorLopez, Yosvanyen
dc.contributor.authorLow, Joshuaen
dc.contributor.authorLysenko, Artemen
dc.contributor.authorMachado, Danielen
dc.contributor.authorMadhukar, Neelen
dc.contributor.authorDe Maeyer, Driesen
dc.contributor.authorMalpartida, Ana Belenen
dc.contributor.authorMamitsuka, Hiroshien
dc.contributor.authorMarabita, Francescoen
dc.contributor.authorMarchal, Kathleenen
dc.contributor.authorMarttinen, Pekkaen
dc.contributor.authorMason, Danielen
dc.contributor.authorMazaheri, Alirezaen
dc.contributor.authorMehmood, Arfaen
dc.contributor.authorMehreen, Alien
dc.contributor.authorMichaut, Magalien
dc.contributor.authorMiller, Ryan A.en
dc.contributor.authorMitsopoulos, Costasen
dc.contributor.authorModos, Dezsoen
dc.contributor.authorVan Moerbeke, Marijkeen
dc.contributor.authorMoo, Keaganen
dc.contributor.authorMotsinger-Reif, Alisonen
dc.contributor.authorMovva, Rajiven
dc.contributor.authorMuraru, Sebastianen
dc.contributor.authorMuratov, Eugeneen
dc.contributor.authorMushthofa, Mushthofaen
dc.contributor.authorNagarajan, Niranjanen
dc.contributor.authorNakken, Sigveen
dc.contributor.authorNath, Aritroen
dc.contributor.authorNeuvial, Pierreen
dc.contributor.authorNewton, Richarden
dc.contributor.authorNing, Zhengen
dc.contributor.authorDe Niz, Carlosen
dc.contributor.authorOliva, Baldoen
dc.contributor.authorOlsen, Catharinaen
dc.contributor.authorPalmeri, Antonioen
dc.contributor.authorPanesar, Bhawanen
dc.contributor.authorPapadopoulos, Stavrosen
dc.contributor.authorPark, Jaesuben
dc.contributor.authorPark, Seonyeongen
dc.contributor.authorPark, Sungjoonen
dc.contributor.authorPawitan, Yudien
dc.contributor.authorPeluso, Danieleen
dc.contributor.authorPendyala, Sriramen
dc.contributor.authorPeng, Jianen
dc.contributor.authorPerfetto, Liviaen
dc.contributor.authorPirro, Stefanoen
dc.contributor.authorPlevritis, Sylviaen
dc.contributor.authorPoliti, Reginaen
dc.contributor.authorPoon, Hoifungen
dc.contributor.authorPorta, Eduarden
dc.contributor.authorPrellner, Isaken
dc.contributor.authorPreuer, Kristinaen
dc.contributor.authorAngel Pujana, Miguelen
dc.contributor.authorRamnarine, Ricardoen
dc.contributor.authorReid, John E.en
dc.contributor.authorReyal, Fabienen
dc.contributor.authorRichardson, Sylviaen
dc.contributor.authorRicketts, Camiren
dc.contributor.authorRieswijk, Lindaen
dc.contributor.authorRocha, Miguelen
dc.contributor.authorRodriguez-Gonzalvez, Carmenen
dc.contributor.authorRoell, Kyleen
dc.contributor.authorRotroff, Danielen
dc.contributor.authorde Ruiter, Julian R.en
dc.contributor.authorRukawa, Ployen
dc.contributor.authorSadacca, Benjaminen
dc.contributor.authorSafikhani, Zhalehen
dc.contributor.authorSafitri, Fitaen
dc.contributor.authorSales-Pardo, Martaen
dc.contributor.authorSauer, Sebastianen
dc.contributor.authorSchlichting, Moritzen
dc.contributor.authorSeoane, Jose A.en
dc.contributor.authorSerra, Jordien
dc.contributor.authorShang, Ming-Meien
dc.contributor.authorSharma, Aloken
dc.contributor.authorSharma, Harien
dc.contributor.authorShen, Yangen
dc.contributor.authorShiga, Motokien
dc.contributor.authorShin, Moonshiken
dc.contributor.authorShkedy, Ziven
dc.contributor.authorShopsowitz, Kevinen
dc.contributor.authorSinai, Samen
dc.contributor.authorSkola, Dylanen
dc.contributor.authorSmirnov, Petren
dc.contributor.authorSoerensen, Izel Fourieen
dc.contributor.authorSoerensen, Peteren
dc.contributor.authorSong, Je-Hoonen
dc.contributor.authorSong, Sang Oken
dc.contributor.authorSoufan, Othmanen
dc.contributor.authorSpitzmueller, Andreasen
dc.contributor.authorSteipe, Borisen
dc.contributor.authorSuphavilai, Chayapornen
dc.contributor.authorTamayo, Sergio Pulidoen
dc.contributor.authorTamborero, Daviden
dc.contributor.authorTang, Jingen
dc.contributor.authorTanoli, Zia-ur-Rehmanen
dc.contributor.authorTarres-Deulofeu, Marcen
dc.contributor.authorTegner, Jesperen
dc.contributor.authorThommesen, Liven
dc.contributor.authorTonekaboni, Seyed Ali Madanien
dc.contributor.authorTran, Hong T.en
dc.contributor.authorDe Troyer, Ewouden
dc.contributor.authorTruong, Amyen
dc.contributor.authorTsunoda, Tatsuhikoen
dc.contributor.authorTuru, Gaboren
dc.contributor.authorTzeng, Guang-Yoen
dc.contributor.authorVerbeke, Lievenen
dc.contributor.authorVidela, Santiagoen
dc.contributor.authorVis, Danielen
dc.contributor.authorVoronkov, Andreyen
dc.contributor.authorVotis, Konstantinosen
dc.contributor.authorWang, Ashleyen
dc.contributor.authorWang, Hong-Qiang Horaceen
dc.contributor.authorWang, Po-Weien
dc.contributor.authorWang, Shengen
dc.contributor.authorWang, Weien
dc.contributor.authorWang, Xiaochenen
dc.contributor.authorWang, Xinen
dc.contributor.authorWennerberg, Kristeren
dc.contributor.authorWernisch, Lorenzen
dc.contributor.authorWessels, Lodewyken
dc.contributor.authorvan Westen, Gerard J. P.en
dc.contributor.authorWesterman, Bart A.en
dc.contributor.authorWhite, Simon Richarden
dc.contributor.authorWillighagen, Egonen
dc.contributor.authorWurdinger, Tomen
dc.contributor.authorXie, Leien
dc.contributor.authorXie, Shuilianen
dc.contributor.authorXu, Huaen
dc.contributor.authorYadav, Bhagwanen
dc.contributor.authorYau, Christopheren
dc.contributor.authorYeerna, Huwateen
dc.contributor.authorYin, Jia Weien
dc.contributor.authorYu, Michaelen
dc.contributor.authorYu, MinHwanen
dc.contributor.authorYun, So Jeongen
dc.contributor.authorZakharov, Alexeyen
dc.contributor.authorZamichos, Alexandrosen
dc.contributor.authorZanin, Massimilianoen
dc.contributor.authorZeng, Lien
dc.contributor.authorZenil, Hectoren
dc.contributor.authorZhang, Fredericken
dc.contributor.authorZhang, Pengyueen
dc.contributor.authorZhang, Weien
dc.contributor.authorZhao, Hongyuen
dc.contributor.authorZhao, Lanen
dc.contributor.authorZheng, Wenjinen
dc.contributor.authorZoufir, Azedineen
dc.contributor.authorZucknick, Manuelaen
dc.contributor.departmentComputer Scienceen
dc.date.accessioned2019-07-30T16:43:00Zen
dc.date.available2019-07-30T16:43:00Zen
dc.date.issued2019-06-17en
dc.description.abstractThe 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.en
dc.description.notesWe thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194).en
dc.description.sponsorshipAstraZenecaen
dc.description.sponsorshipEuropean Union Horizon 2020 research [668858 PrECISE]en
dc.description.sponsorshipJoint Research Center for Computational Biomedicine (Bayer AG)en
dc.description.sponsorshipNational Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciencesen
dc.description.sponsorshipWellcome Trust [102696, 206194]en
dc.identifier.doihttps://doi.org/10.1038/s41467-019-09799-2en
dc.identifier.issn2041-1723en
dc.identifier.other2674en
dc.identifier.pmid31209238en
dc.identifier.urihttp://hdl.handle.net/10919/92046en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleCommunity assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screenen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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