An interactive web application for processing, correcting, and visualizing genome-wide pooled CRISPR-Cas9 screens

• Published in: Cell reports methods Vol. 3; no. 1; p. 100373
• Main Authors: Vinceti, Alessandro, De Lucia, Riccardo Roberto, Cremaschi, Paolo, Perron, Umberto, Karakoc, Emre, Mauri, Luca, Fernandez, Carlos, Kluczynski, Krzysztof Henryk, Anderson, Daniel Stephen, Iorio, Francesco
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-01-2023; Elsevier
• Subjects: bias correction; cancer dependency; copy number; CRISPR-Cas9 screens; data exploration; data visualization; gene essentiality; post-genomic data; unsupervised analysis; web application; CP: biotechnology; gene essentiality; CRISPR-Cas9 screens; bias correction; web application; unsupervised analysis; post-genomic data; CP: systems biology; data exploration; data visualization; copy number; cancer dependency
• ISSN: 2667-2375; 2667-2375
• DOI: 10.1016/j.crmeth.2022.100373

A limitation of pooled CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes arising from copy-number-amplified genomics regions. To solve this issue, we previously developed CRISPRcleanR: a computational method implemented as R/python package and in a dockerized version. CRISPRcleanR detects and corrects biased responses to CRISPR-Cas9 targeting in an unsupervised fashion, accurately reducing false-positive signals while maintaining sensitivity in identifying relevant genetic dependencies. Here, we present CRISPRcleanRWebApp, a web application enabling access to CRISPRcleanR through an intuitive interface. CRISPRcleanRWebApp removes the complexity of R/python language user interactions; provides user-friendly access to a complete analytical pipeline, not requiring any data pre-processing and generating gene-level summaries of essentiality with associated statistical scores; and offers a range of interactively explorable plots while supporting a more comprehensive range of CRISPR guide RNAs’ libraries than the original package. CRISPRcleanRWebApp is available at https://crisprcleanr-webapp.fht.org/.
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•CRISPRcleanR corrects biases in CRISPR-Cas9 screens•CRISPRcleanRWebApp is a web-based, user-friendly front end for CRISPRcleanR•CRISPRcleanRWebApp processes raw sequencing files and produces interactive results
Several computational tools exist for correcting gene-independent responses to CRISPR-Cas9 targeting. Among these, CRISPRcleanR has been the first to correct such biases in an unsupervised manner (i.e., not requiring input copy-number data of the screened model). To broaden the CRISPRcleanR user base, we enriched it with original functionalities and developed CRISPRcleanRWebApp, a web application front-end to the CRISPRcleanR R package. CRISPRcleanRWebApp provides an intuitive graphical interface and automated workflows for complete CRISPR-Cas9 data processing, analysis, and visualization.
A major problem affecting CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes found in copy-number-amplified regions. Vinceti et al. present CRISPRcleanRWebApp, a web application based on the CRISPRcleanR R package that corrects such biases in an unsupervised manner. CRISPRcleanRWebApp provides an intuitive and user-friendly graphical interface.