%0 Journal Article %J Nat Commun %D 2019 %T Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen. %A Menden, Michael P %A Wang, Dennis %A Mason, Mike J %A Szalai, Bence %A Bulusu, Krishna C %A Guan, Yuanfang %A Yu, Thomas %A Kang, Jaewoo %A Jeon, Minji %A Wolfinger, Russ %A Nguyen, Tin %A Zaslavskiy, Mikhail %A Jang, In Sock %A Ghazoui, Zara %A Ahsen, Mehmet Eren %A Vogel, Robert %A Neto, Elias Chaibub %A Norman, Thea %A Tang, Eric K Y %A Garnett, Mathew J %A Veroli, Giovanni Y Di %A Fawell, Stephen %A Stolovitzky, Gustavo %A Guinney, Justin %A Dry, Jonathan R %A Saez-Rodriguez, Julio %K ADAM17 Protein %K Antineoplastic Combined Chemotherapy Protocols %K Benchmarking %K Biomarkers, Tumor %K Cell Line, Tumor %K Computational Biology %K Datasets as Topic %K Drug Antagonism %K Drug Resistance, Neoplasm %K Drug Synergism %K Genomics %K Humans %K Molecular Targeted Therapy %K mutation %K Neoplasms %K pharmacogenetics %K Phosphatidylinositol 3-Kinases %K Phosphoinositide-3 Kinase Inhibitors %K Treatment Outcome %X

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.

%B Nat Commun %V 10 %P 2674 %8 2019 06 17 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/31209238?dopt=Abstract %R 10.1038/s41467-019-09799-2 %0 Journal Article %J Brief Bioinform %D 2008 %T Interoperability with Moby 1.0--it's better than sharing your toothbrush! %A Wilkinson, Mark D %A Senger, Martin %A Kawas, Edward %A Bruskiewich, Richard %A Gouzy, Jerome %A Noirot, Celine %A Bardou, Philippe %A Ng, Ambrose %A Haase, Dirk %A Saiz, Enrique de Andres %A Wang, Dennis %A Gibbons, Frank %A Gordon, Paul M K %A Sensen, Christoph W %A Carrasco, Jose Manuel Rodriguez %A Fernández, José M %A Shen, Lixin %A Links, Matthew %A Ng, Michael %A Opushneva, Nina %A Neerincx, Pieter B T %A Leunissen, Jack A M %A Ernst, Rebecca %A Twigger, Simon %A Usadel, Bjorn %A Good, Benjamin %A Wong, Yan %A Stein, Lincoln %A Crosby, William %A Karlsson, Johan %A Royo, Romina %A Párraga, Iván %A Ramírez, Sergio %A Gelpi, Josep Lluis %A Trelles, Oswaldo %A Pisano, David G %A Jimenez, Natalia %A Kerhornou, Arnaud %A Rosset, Roman %A Zamacola, Leire %A Tárraga, Joaquín %A Huerta-Cepas, Jaime %A Carazo, Jose María %A Dopazo, Joaquin %A Guigó, Roderic %A Navarro, Arcadi %A Orozco, Modesto %A Valencia, Alfonso %A Claros, M Gonzalo %A Pérez, Antonio J %A Aldana, Jose %A Rojano, M Mar %A Fernandez-Santa Cruz, Raul %A Navas, Ismael %A Schiltz, Gary %A Farmer, Andrew %A Gessler, Damian %A Schoof, Heiko %A Groscurth, Andreas %K Computational Biology %K Database Management Systems %K Databases, Factual %K Information Storage and Retrieval %K Internet %K Programming Languages %K Systems Integration %X

The BioMoby project was initiated in 2001 from within the model organism database community. It aimed to standardize methodologies to facilitate information exchange and access to analytical resources, using a consensus driven approach. Six years later, the BioMoby development community is pleased to announce the release of the 1.0 version of the interoperability framework, registry Application Programming Interface and supporting Perl and Java code-bases. Together, these provide interoperable access to over 1400 bioinformatics resources worldwide through the BioMoby platform, and this number continues to grow. Here we highlight and discuss the features of BioMoby that make it distinct from other Semantic Web Service and interoperability initiatives, and that have been instrumental to its deployment and use by a wide community of bioinformatics service providers. The standard, client software, and supporting code libraries are all freely available at http://www.biomoby.org/.

%B Brief Bioinform %V 9 %P 220-31 %8 2008 May %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/18238804?dopt=Abstract %R 10.1093/bib/bbn003