Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects

作者：Joshua M. Dempster, Isabella Boyle, Francisca Vázquez, David E. Root, Jesse S. Boehm, William C. Hahn, Aviad Tsherniak, James M. McFarland · 发表于：Genome biology · 年份：2021 · DOI：10.1186/s13059-021-02540-7 · 被引用次数：427 · 研究领域：CRISPR and Genetic Engineering、Evolution and Genetic Dynamics、Gene Regulatory Network Analysis

CRISPR loss of function screens are powerful tools to interrogate biology but exhibit a number of biases and artifacts that can confound the results. Here, we introduce Chronos, an algorithm for inferring gene knockout fitness effects based on an explicit model of cell proliferation dynamics after CRISPR gene knockout. We test Chronos on two pan-cancer CRISPR datasets and one longitudinal CRISPR screen. Chronos generally outperforms competitors in separation of controls and strength of biomarker associations, particularly when longitudinal data is available. Additionally, Chronos exhibits the lowest copy number and screen quality bias of evaluated methods. Chronos is available at https://github.com/broadinstitute/chronos .