ArticleGenome biology2019
Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Multi-omics analysis identifies GINS1 as a prognostic biomarker in lung adenocarcinoma, linked to macrophage polarization and tumor cell survival.Discover oncology · 2026Article
- CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability.Journal of pharmaceutical analysis · 2026Review
- Comparative Analysis of CRISPR/Cas9 Delivery Methods in Marine Teleost Cell Lines.International journal of molecular sciences · 2025Article
- Revealing genetic drivers of ovarian cancer and chemoresistance: insights from whole-genome CRISPR-knockout library screens.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- The present and future of the Cancer Dependency Map.Nature reviews. Cancer · 2025Review
- CRISPR/Cas9-based discovery of ccRCC therapeutic opportunities through molecular mechanism and immune microenvironment analysis.Frontiers in immunology · 2025Article
- A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data.Genome biology · 2024Article
- Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries.Nature communications · 2024Article
- Prognostic and chemotherapeutic response prediction by proliferation essential gene signature: Investigating POLE2 in bladder cancer progression and cisplatin resistance.Journal of Cancer · 2024Article
- Precise homology-directed installation of large genomic edits in human cells with cleaving and nicking high-specificity Cas9 variants.Nucleic acids research · 2023Article
- Article
- An interactive web application for processing, correcting, and visualizing genome-wide pooled CRISPR-Cas9 screens.Cell reports methods · 2023Article
- Review
- High-content CRISPR screening.Nature reviews. Methods primers · 2022Article
- Common computational tools for analyzing CRISPR screens.Emerging topics in life sciences · 2021Review
- Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects.Genome biology · 2021Article
- CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens.BMC genomics · 2021Article
- A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing.Nature communications · 2021Article
- Genome-wide interrogation of gene functions through base editor screens empowered by barcoded sgRNAs.Nature biotechnology · 2021Article
- Integrated cross-study datasets of genetic dependencies in cancer.Nature communications · 2021Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundCRISPR-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.
resultsUtilizing 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 duplication 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.
conclusionOur analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing in cancer cells.
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