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Biology subjects

Kalinka, A.

Publications and source records attributed to Kalinka, A..

2 recordsLinked to original sources

Controlling False Discovery in CRISPR Screens

Excluding false positives is critical for interpreting CRISPR screens. Here, we introduce a new Chronos module for estimating false discovery rates for identifying knockouts that cause loss of viability or have differential viability effects in different conditions. We introduce a rigorous benchmarking framework using real CRISPR data. We show with multiple real datasets that existing methods such as MAGeCK are miscalibrated and can generate uncontrolled numbers of false positives even after multiple hypothesis correction. Only Chronos correctly controls false discovery for all tested tasks. Additionally, Chronoss estimates are well-calibrated, allowing users to accurately specify the acceptable false discovery rate.

bioinformatics↗

A benchmark comparison of CRISPRn guide-RNA design algorithms and generation of small single and dual-targeting libraries to boost screening efficiency

Genome-wide CRISPR sgRNA libraries have emerged as transformative tools to systematically probe gene function. While these libraries have been iterated over time to be more efficient, their large size limits their use in some applications. Here, we benchmarked publicly available genome-wide single-targeting sgRNA libraries and evaluated dual targeting as a strategy for pooled CRISPR loss-of-function screens. We leveraged this data to design two minimal genome-wide human CRISPR-Cas9 libraries that are 50% smaller than other libraries and that preserve specificity and sensitivity, thus enabling broader deployment at scale.

molecular biology↗