title: Assessment of pharmacogenomic agreement.
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 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.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Zhaleh
authors.initials: Z
authors.lastname: Safikhani
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, Quebec, H2W 1R7, Canada.
authors.forename: Nehme
authors.initials: N
authors.lastname: El-Hachem
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Rene
authors.initials: R
authors.lastname: Quevedo
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Petr
authors.initials: P
authors.lastname: Smirnov
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Department of Computer Science, University of Toronto, Toronto, Ontario, M5S 2E4, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Goldenberg
authors.affiliation: University College London, London, WC1E 6BT, UK.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Juul Birkbak
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, 10065, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, 10021, USA; The Feil Family Brain and Mind Research Institute (BMRI), New York, NY, 10065, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Mason
authors.affiliation: Section of Medical Oncology, Yale School of Medicine, New Haven, CT, 06520, USA; Yale Cancer Center, Yale University, New Haven, CT, 06510, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Hatzis
authors.affiliation: Fudan University, Shanghai City, 200135, China; University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Leming
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA; Department of Radiation Oncology and Radiology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02215, USA.
authors.forename: Hugo Jwl
authors.initials: HJ
authors.lastname: Aerts
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA; Department of Biostatistics and Computational Biology and Center for Cancer Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada; Department of Computer Science, University of Toronto, Toronto, Ontario, M5S 2E4, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
keywords: Bioinformatics; Biomarkers; Cancer Cell Lines; Drug Response; Experimental Design; High-Throughput Screening; Pharmacogenomics; Statistics