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However, the assumption that CRISPR screens are saturating has been largely untested. Through integrated analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we show that a typical CRISPR screen has a \u223c20% false negative rate, in addition to library-specific false negatives. Replicability falls sharply as gene expression decreases, while cancer subtype-specific genes within a tissue show distinct profiles compared to false negatives. Cumulative analyses across tissues improves our understanding of core essential genes and suggest only a small number of lineage-specific essential genes, enriched for transcription factors that define pathways of tissue differentiation. To recover false negatives, we introduce a method, Joint Log Odds of Essentiality (JLOE), which builds on our prior work with BAGEL to selectively rescue the false negatives without an increased false discovery rate.<\/jats:p>","DOI":"10.1093\/nar\/gkad046","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T13:55:06Z","timestamp":1673963706000},"page":"1637-1651","source":"Crossref","is-referenced-by-count":9,"title":["Recovering false negatives in CRISPR fitness screens with JLOE"],"prefix":"10.1093","volume":"51","author":[{"given":"Merve","family":"Dede","sequence":"first","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston , TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1880-3341","authenticated-orcid":false,"given":"Traver","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston , TX, USA"},{"name":"Department of Cancer Biology, The University of Texas MD Anderson Cancer Center , Houston , TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"2023040808302540900_","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1101\/SQB.1951.016.01.006","article-title":"Some recent studies bearing on the one gene-one enzyme hypothesis","volume":"16","author":"Horowitz","year":"1951","journal-title":"Cold Spring Harb. 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