Journal Article

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

Boyle, Isabella, Boehm, Jesse S., Hahn, William C., McFarland, James M., Vazquez, Francisca, Tsherniak, Aviad, Root, David E., Dempster, Joshua M.

2021

Overview

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 .

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Algorithms / Animal Genetics and Genomics / Bias / Bioinformatics / biomarkers / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Cell growth / Cell proliferation / Cloning / Clustered Regularly Interspaced Short Palindromic Repeats / Computational Biology / Copy number / CRISPR / CRISPR-Cas Systems / data collection / dynamic models / Evolutionary Biology / Experiments / Fitness / Gene Knockout Techniques / Gene Library / gene targeting / Genes / Genome / Genomes / Genotype & phenotype / Human Genetics / Humans / Infections / Life Sciences / Method / Methods / Microbial Genetics and Genomics / Mutation / Neoplasms - genetics / Plant Genetics and Genomics / Population Dynamics