Safikhani Zhaleh, El-Hachem Nehme, Quevedo Rene, Smirnov Petr, Goldenberg Anna, Juul Birkbak Nicolai, Mason Christopher, Hatzis Christos, Shi Leming, Aerts Hugo Jwl, Quackenbush John, Haibe-Kains Benjamin
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
Institut de recherches cliniques de Montréal, Montreal, Quebec, H2W 1R7, Canada.
F1000Res. 2016 May 9;5:825. doi: 10.12688/f1000research.8705.1. eCollection 2016.
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.
2013年，我们发表了一项分析，证明在两项独立的大规模药物基因组学筛选——癌症药物敏感性基因组学（GDSC）和癌细胞系百科全书（CCLE）中报告的药物反应数据和基因-药物关联是不一致的。GDSC和CCLE的研究人员最近报告称，他们各自的研究显示出合理的一致性，并产生了相似的药物反应分子预测指标，这似乎与我们之前的发现相矛盾。重新分析作者发表的方法和结果后，我们发现他们的分析没有考虑基因组数据的变异性，更重要的是，他们比较了每项研究中不同的药物敏感性测量指标，这与我们更严格的一致性评估有很大偏差。我们对GDSC和CCLE最新的基因组和药理学数据进行比较，证实了我们之前发表的发现，即这两组报告的药物反应测量指标不一致。我们认为，在设想将药物敏感性预测指标转化为临床应用之前，采用一种有原则的方法来评估其可重复性是必要的。
