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Assessment of pharmacogenomic agreement

Zhaleh Safikhani, Nehme El-Hachem, Rene Quevedo, Petr Smirnov, Anna Goldenberg, Nicolai Juul Birkbak, Christopher E. Mason, Christos Hatzis, Leming Shi, Hugo JWL Aerts, John Quackenbush, Benjamin Haibe-Kains
doi: https://doi.org/10.1101/048470
Zhaleh Safikhani
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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Nehme El-Hachem
3Institut de recherches cliniques de Montréal, Montreal, Quebec, Canada
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Rene Quevedo
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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Petr Smirnov
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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Anna Goldenberg
4Hospital for Sick Children, Toronto, Ontario, Canada
5Department of Computer Science, University of Toronto, Toronto, Ontario, Canada
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Nicolai Juul Birkbak
6University College London, London, United Kingdom
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Christopher E. Mason
7Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA
8The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA,
9The Feil Family Brain and Mind Research Institute (BMRI), New York, NY, USA
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Christos Hatzis
10Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut; USA
11Yale Cancer Center, Yale University, New Haven, Connecticut, USA
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Leming Shi
12Fudan University, Shanghai City, China
13University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Hugo JWL Aerts
14Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. USA
15Department of Radiation Oncology and Radiology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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John Quackenbush
16Department of Biostatistics and Computational Biology and Center for Cancer Computational Biology, Boston, Massachusetts, USA
17Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
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Benjamin Haibe-Kains
1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
5Department of Computer Science, University of Toronto, Toronto, Ontario, Canada
9The Feil Family Brain and Mind Research Institute (BMRI), New York, NY, USA
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Abstract

In 2013 we published an analysis demonstrating that drug response data and gene-drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer1 (GDSC) and Cancer Cell Line Encyclopedia2 (CCLE), were inconsistent3. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response4, seemingly contradicting our previous findings3. Reanalyzing the authors’ published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent5. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 13, 2016.
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Assessment of pharmacogenomic agreement
Zhaleh Safikhani, Nehme El-Hachem, Rene Quevedo, Petr Smirnov, Anna Goldenberg, Nicolai Juul Birkbak, Christopher E. Mason, Christos Hatzis, Leming Shi, Hugo JWL Aerts, John Quackenbush, Benjamin Haibe-Kains
bioRxiv 048470; doi: https://doi.org/10.1101/048470
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Assessment of pharmacogenomic agreement
Zhaleh Safikhani, Nehme El-Hachem, Rene Quevedo, Petr Smirnov, Anna Goldenberg, Nicolai Juul Birkbak, Christopher E. Mason, Christos Hatzis, Leming Shi, Hugo JWL Aerts, John Quackenbush, Benjamin Haibe-Kains
bioRxiv 048470; doi: https://doi.org/10.1101/048470

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