CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens

Abstract Background CRISPR-Cas9 genome-wide screens are being increasingly performed, allowing systematic explorations of cancer dependencies at unprecedented accuracy and scale. One of the major computational challenges when analysing data derived from such screens is to identify genes that are ess...

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Autores principales:	Alessandro Vinceti, Emre Karakoc, Clare Pacini, Umberto Perron, Riccardo Roberto De Lucia, Mathew J. Garnett, Francesco Iorio
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	CRISPR-Cas9 screens core-fitness genes cancer dependency algorithms benchmark Biotechnology TP248.13-248.65 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/f7df6232fdbd4a2691e1047e936b4957
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spelling	oai:doaj.org-article:f7df6232fdbd4a2691e1047e936b49572021-11-21T12:26:26ZCoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens10.1186/s12864-021-08129-51471-2164https://doaj.org/article/f7df6232fdbd4a2691e1047e936b49572021-11-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-08129-5https://doaj.org/toc/1471-2164Abstract Background CRISPR-Cas9 genome-wide screens are being increasingly performed, allowing systematic explorations of cancer dependencies at unprecedented accuracy and scale. One of the major computational challenges when analysing data derived from such screens is to identify genes that are essential for cell survival invariantly across tissues, conditions, and genomic-contexts (core-fitness genes), and to distinguish them from context-specific essential genes. This is of paramount importance to assess the safety profile of candidate therapeutic targets and for elucidating mechanisms involved in tissue-specific genetic diseases. Results We have developed CoRe: an R package implementing existing and novel methods for the identification of core-fitness genes (at two different level of stringency) from joint analyses of multiple CRISPR-Cas9 screens. We demonstrate, through a fully reproducible benchmarking pipeline, that CoRe outperforms state-of-the-art tools, yielding more reliable and biologically relevant sets of core-fitness genes. Conclusions CoRe offers a flexible pipeline, compatible with many pre-processing methods for the analysis of CRISPR data, which can be tailored onto different use-cases. The CoRe package can be used for the identification of high-confidence novel core-fitness genes, as well as a means to filter out potentially cytotoxic hits while analysing cancer dependency datasets for identifying and prioritising novel selective therapeutic targets.Alessandro VincetiEmre KarakocClare PaciniUmberto PerronRiccardo Roberto De LuciaMathew J. GarnettFrancesco IorioBMCarticleCRISPR-Cas9 screenscore-fitness genescancer dependencyalgorithmsbenchmarkBiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CRISPR-Cas9 screens core-fitness genes cancer dependency algorithms benchmark Biotechnology TP248.13-248.65 Genetics QH426-470
spellingShingle	CRISPR-Cas9 screens core-fitness genes cancer dependency algorithms benchmark Biotechnology TP248.13-248.65 Genetics QH426-470 Alessandro Vinceti Emre Karakoc Clare Pacini Umberto Perron Riccardo Roberto De Lucia Mathew J. Garnett Francesco Iorio CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
description	Abstract Background CRISPR-Cas9 genome-wide screens are being increasingly performed, allowing systematic explorations of cancer dependencies at unprecedented accuracy and scale. One of the major computational challenges when analysing data derived from such screens is to identify genes that are essential for cell survival invariantly across tissues, conditions, and genomic-contexts (core-fitness genes), and to distinguish them from context-specific essential genes. This is of paramount importance to assess the safety profile of candidate therapeutic targets and for elucidating mechanisms involved in tissue-specific genetic diseases. Results We have developed CoRe: an R package implementing existing and novel methods for the identification of core-fitness genes (at two different level of stringency) from joint analyses of multiple CRISPR-Cas9 screens. We demonstrate, through a fully reproducible benchmarking pipeline, that CoRe outperforms state-of-the-art tools, yielding more reliable and biologically relevant sets of core-fitness genes. Conclusions CoRe offers a flexible pipeline, compatible with many pre-processing methods for the analysis of CRISPR data, which can be tailored onto different use-cases. The CoRe package can be used for the identification of high-confidence novel core-fitness genes, as well as a means to filter out potentially cytotoxic hits while analysing cancer dependency datasets for identifying and prioritising novel selective therapeutic targets.
format	article
author	Alessandro Vinceti Emre Karakoc Clare Pacini Umberto Perron Riccardo Roberto De Lucia Mathew J. Garnett Francesco Iorio
author_facet	Alessandro Vinceti Emre Karakoc Clare Pacini Umberto Perron Riccardo Roberto De Lucia Mathew J. Garnett Francesco Iorio
author_sort	Alessandro Vinceti
title	CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
title_short	CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
title_full	CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
title_fullStr	CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
title_full_unstemmed	CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
title_sort	core: a robustly benchmarked r package for identifying core-fitness genes in genome-wide pooled crispr-cas9 screens
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f7df6232fdbd4a2691e1047e936b4957
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CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens

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