ArticleNature biotechnology2020
Genetic interaction mapping and exon-resolution functional genomics with a hybrid Cas9-Cas12a platform.
Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 146 citations in OpenAlex.
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- Analysis of Combinatorial Knockout CRISPR Screens with GRAPE: Genetic interaction Regression Analysis of Pairwise Effects.bioRxiv : the preprint server for biology · 2026Article
- Splice isoform-perturbation coupled to single cell transcriptome profiling reveals functions of microexons in neurogenesis and autism-linked pathways.Nature communications · 2026Article
- Single-cell exon deletion profiling reveals splicing events that shape gene expression and cell state dynamics.Nature communications · 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
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- Search-and-remove genome editing allows selection of cells by DNA sequence.Nature communications · 2025Article
- 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
- Cas13d-mediated isoform-specific RNA knockdown with a unified computational and experimental toolbox.Nature communications · 2025Article
- Z-scores outperform similar methods for analyzing CRISPR paralog synthetic lethality screens.Genome biology · 2025Article
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- BaCoN (Balanced Correlation Network) improves prediction of gene buffering.Molecular systems biology · 2025Article
- The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.Nature genetics · 2025Article
- CRISPR GENome and epigenome engineering improves loss-of-function genetic-screening approaches.Cell reports methods · 2025Article
27 more citing papers are in PubMed but not listed here.
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13 authors at 2 institutions in 2 countries.
Funding
Abstract
Systematic mapping of genetic interactions (GIs) and interrogation of the functions of sizable genomic segments in mammalian cells represent important goals of biomedical research. To advance these goals, we present a CRISPR (clustered regularly interspaced short palindromic repeats)-based screening system for combinatorial genetic manipulation that employs coexpression of CRISPR-associated nucleases 9 and 12a (Cas9 and Cas12a) and machine-learning-optimized libraries of hybrid Cas9-Cas12a guide RNAs. This system, named Cas Hybrid for Multiplexed Editing and screening Applications (CHyMErA), outperforms genetic screens using Cas9 or Cas12a editing alone. Application of CHyMErA to the ablation of mammalian paralog gene pairs reveals extensive GIs and uncovers phenotypes normally masked by functional redundancy. Application of CHyMErA in a chemogenetic interaction screen identifies genes that impact cell growth in response to mTOR pathway inhibition. Moreover, by systematically targeting thousands of alternative splicing events, CHyMErA identifies exons underlying human cell line fitness. CHyMErA thus represents an effective screening approach for GI mapping and the functional analysis of sizable genomic regions, such as alternative exons.
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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.