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Assessment of Genetic Drift in Large Pharmacogenomic Studies.
Cell Systems ( IF 9.0 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.cels.2020.08.012
Rene Quevedo 1 , Petr Smirnov 1 , Denis Tkachuk 2 , Chantal Ho 2 , Nehme El-Hachem 3 , Zhaleh Safikhani 1 , Trevor J Pugh 4 , Benjamin Haibe-Kains 5
Affiliation  

Genomic instability affects the reproducibility of experiments that rely on cancer cell lines. However, measuring the genomic integrity of these cells throughout a study is a costly endeavor that is commonly forgone. Here, we validate the identity of cancer cell lines in three pharmacogenomic studies and screen for genetic drift within and between datasets. Using SNP data from these datasets encompassing 1,497 unique cell lines and 63 unique pharmacological compounds, we show that genetic drift is widely prevalent in almost all cell lines with a median of 4.5%–6.1% of the total genome size drifted between any two isogenic cell lines. This study highlights the need for molecular profiling of cell lines to minimize the effects of passaging or misidentification in biomedical studies. We developed the CCLid web application, available at www.cclid.ca, to allow users to screen the genomic profiles of their cell lines against these datasets. A record of this paper’s transparent peer review process is included in the Supplemental Information.



中文翻译:

大型药物基因组学研究中的遗传漂移评估。

基因组不稳定性影响依赖癌细胞系的实验的可重复性。然而,在整个研究中测量这些细胞的基因组完整性是一项成本高昂的工作,通常会被放弃。在这里,我们验证了三项药物基因组学研究中癌细胞系的身份,并筛选数据集内和数据集之间的遗传漂移。使用来自这些数据集的 SNP 数据,包括 1,497 个独特的细胞系和 63 个独特的药理学化合物,我们表明遗传漂移在几乎所有细胞系中广泛存在,在任何两个同基因细胞之间漂移的总基因组大小的中位数为 4.5%–6.1%线。这项研究强调需要对细胞系进行分子分析,以最大限度地减少生物医学研究中传代或错误识别的影响。我们开发了 CCLid 网络应用程序,可从 www.cclid.ca 获得,允许用户根据这些数据集筛选其细胞系的基因组谱。本文的透明同行评审过程的记录包含在补充信息中。

更新日期:2020-10-30
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