ArticleGenome biology2020
Multiplex enCas12a screens detect functional buffering among paralogs otherwise masked in monogenic Cas9 knockout screens.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 110 citations in OpenAlex.
- Crosstalk between alternative splicing and non-coding RNAs in hepatocellular carcinoma: from regulatory mechanism to therapeutic implications.Non-coding RNA research · 2026Review
- p190A/ARHGAP35 and p190B/ARHGAP5 proteins in endometrial cancer: a novel cancer-relevant paralog interplay.Molecular oncology · 2026Article
- Article
- Double-CRISPR Knockout Simulation (DKOsim): A Monte-Carlo randomization system to model cell growth behavior and infer the optimal library design for growth-based double knockout screens.PLoS computational biology · 2026Article
- Uncovering cancer dependencies in peptide-interacting protein pockets.bioRxiv : the preprint server for biology · 2026Article
- dHyperCas12a enables multiplexed CRISPRi screens.Nature communications · 2026Article
- Analysis of Combinatorial Knockout CRISPR Screens with GRAPE: Genetic interaction Regression Analysis of Pairwise Effects.bioRxiv : the preprint server for biology · 2026Article
- RNA-coupled CRISPR screens reveal ZNF207 as a regulator of LMNA aberrant splicing in progeria.Molecular cell · 2026Article
- Quantitative analysis of genetic interactions in human cells from genome-wide CRISPR-Cas9 screens.bioRxiv : the preprint server for biology · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- A next-generation dual guide CRISPR system for genetic interaction library screening.Nature communications · 2025Article
- Efficient and multiplexed somatic genome editing with Cas12a mice.Nature biomedical engineering · 2025Article
- Methods and applications of in vivo CRISPR screening.Nature reviews. Genetics · 2025Review
- A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.Genome biology · 2025Article
- Benchmarking genetic interaction scoring methods for identifying synthetic lethality from combinatorial CRISPR screens.NAR genomics and bioinformatics · 2025Article
- Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.Molecular systems biology · 2025Article
- CROPseq-multi: a universal solution for multiplexed perturbation in high-content pooled CRISPR screens.bioRxiv : the preprint server for biology · 2025Article
- HyperCas12a enables multiplexed CRISPRi screens.bioRxiv : the preprint server for biology · 2025Article
- Z-scores outperform similar methods for analyzing CRISPR paralog synthetic lethality screens.Genome biology · 2025Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPooled library CRISPR/Cas9 knockout screening across hundreds of cell lines has identified genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the number of essential genes detected from these monogenic knockout screens is low compared to the number of constitutively expressed genes in a cell.
resultsThrough a systematic analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we observe that half of all constitutively expressed genes are never detected in any CRISPR screen and that these never-essentials are highly enriched for paralogs. We investigated functional buffering among approximately 400 candidate paralog pairs using CRISPR/enCas12a dual-gene knockout screening in three cell lines. We observe 24 synthetic lethal paralog pairs that have escaped detection by monogenic knockout screens at stringent thresholds. Nineteen of 24 (79%) synthetic lethal interactions are present in at least two out of three cell lines and 14 of 24 (58%) are present in all three cell lines tested, including alternate subunits of stable protein complexes as well as functionally redundant enzymes.
conclusionsTogether, these observations strongly suggest that functionally redundant paralogs represent a targetable set of genetic dependencies that are systematically under-represented among cell-essential genes in monogenic CRISPR-based loss of function screens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.