Assessment of pharmacogenomic agreement [version 1; referees: 3 approved]
Zhaleh Safikhani,
Nehme El-Hachem,
Rene Quevedo,
Petr Smirnov,
Anna Goldenberg,
Nicolai Juul Birkbak,
Christopher Mason,
Christos Hatzis,
Leming Shi,
Hugo JWL Aerts,
John Quackenbush,
Benjamin Haibe-Kains
Affiliations
Zhaleh Safikhani
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada
Nehme El-Hachem
Institut de recherches cliniques de Montréal, Montreal, Quebec, H2W 1R7, Canada
Rene Quevedo
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada
Petr Smirnov
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada
Anna Goldenberg
Department of Computer Science, University of Toronto, Toronto, Ontario, M5S 2E4, Canada
Nicolai Juul Birkbak
University College London, London, WC1E 6BT, UK
Christopher Mason
The Feil Family Brain and Mind Research Institute (BMRI), New York, NY, 10065, USA
Christos Hatzis
Yale Cancer Center, Yale University, New Haven, CT, 06510, USA
Leming Shi
University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA
Hugo JWL Aerts
Department of Radiation Oncology and Radiology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02215, USA
John Quackenbush
Department of Biostatistics and Computational Biology and Center for Cancer Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA
Benjamin Haibe-Kains
Department of Computer Science, University of Toronto, Toronto, Ontario, M5S 2E4, Canada
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 Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were inconsistent. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response, seemingly contradicting our previous findings. 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 consistent. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings.
