Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects.

Dataset ID Technology Samples
EGAD00001004124 Illumina HiSeq 2000 12

Dataset Description

CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed. Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene independent manner. In contrast, amplifications caused by whole chromosomal duplications have little to no impact on fitness. This effect is cell line specific and dependent on the ploidy status. We devise a copy-number ratio metric that substantially improves the detection of gene-independent cell fitness effects in CRISPR-Cas9 screens. Furthermore, we develop a computational tool, called Crispy, to account for these effects on a single sample basis and provide corrected gene fitness effects. Our analysis demonstrates the importance of structural rearrangements in mediating the ... (Show More)

Data Use Conditions

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Label Code Version Modifier
general research use and clinical care DUO:0000005 2017-10-16
research use only DUO:0000014 2017-10-16
publication required DUO:0000019 2017-10-16
user specific restriction DUO:0000026 2017-10-16
institution specific restriction DUO:0000028 2017-10-16