PT - JOURNAL ARTICLE AU - Bernhard Schmierer AU - Sandeep K. Botla AU - Jilin Zhang AU - Mikko Turunen AU - Teemu Kivioja AU - Jussi Taipale TI - CRISPR/Cas9 screening using unique molecular identifiers AID - 10.1101/114355 DP - 2017 Jan 01 TA - bioRxiv PG - 114355 4099 - http://biorxiv.org/content/early/2017/05/15/114355.short 4100 - http://biorxiv.org/content/early/2017/05/15/114355.full AB - Loss of function screening by CRISPR/Cas9 gene knockout with pooled, lentiviral guide libraries is a widely applicable method for systematic identification of genes contributing to diverse cellular phenotypes. Here, random sequence labels (RSLs) are incorporated into the guide library, which act as unique molecular identifiers (UMIs) to allow massively parallel lineage tracing and lineage dropout screening. RSLs greatly improve the reproducibility of results by increasing both the precision and the accuracy of screens. They reduce the number of cells and sequencing reads needed to reach a set statistical power, or allow a more robust screen using the same number of cells.