ArticleNucleic acids research2021
Minimized combinatorial CRISPR screens identify genetic interactions in autophagy.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer.The EMBO journal · 2026Article
- Genome-scale mapping of variant, enhancer and gene function in primary human CD4+ T cells.bioRxiv : the preprint server for biology · 2026Article
- Time-resolved functional genomics using deep learning reveals global hierarchical control of autophagy.Nature cell biology · 2026Article
- Disrupting the TGF-β-regulated epithelial-mesenchymal transition, apoptotic and autophagic phenotypes of 3D glioblastoma spheroids via glycolytic inhibition.Exploration of targeted anti-tumor therapy · 2026Article
- Multi-scale classification decodes the complexity of the human E3 ligome.Nature communications · 2025Article
- A next-generation dual guide CRISPR system for genetic interaction library screening.Nature communications · 2025Article
- Applications of Genome-wide Screening of CRISPR/Cas9 Knockout Library in Identifying Novel Molecular Targets for Xenobiotics.Environment & health (Washington, D.C.) · 2025Review
- A multi-layer encoder prediction model for individual sample specific gene combination effect (MLEC-iGeneCombo).PLoS computational biology · 2025Article
- CRISPR GENome and epigenome engineering improves loss-of-function genetic-screening approaches.Cell reports methods · 2025Article
- The double role of GABAergic system in systemic tumors: an updated review.Frontiers in oncology · 2025Review
- Ribosome rescue factor PELOTA modulates translation start site choice for C/EBPα protein isoforms.Life science alliance · 2024Article
- Genome-scale pan-cancer interrogation of lncRNA dependencies using CasRx.Nature methods · 2024Article
- Article
- Compact CRISPR genetic screens enabled by improved guide RNA library cloning.Genome biology · 2024Article
- SLKB: synthetic lethality knowledge base.Nucleic acids research · 2024Article
- Deciphering the mitophagy receptor network identifies a crucial role for OPTN (optineurin) in acute myeloid leukemia.Autophagy · 2023Article
- A dual sgRNA library design to probe genetic modifiers using genome-wide CRISPRi screens.BMC genomics · 2023Article
- The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension.Communications biology · 2023Article
- ReCo: automated NGS read-counting of single and combinatorial CRISPR gRNAs.Bioinformatics (Oxford, England) · 2023Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs multiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed combinatorial CRISPR libraries. We demonstrate that the library distribution skew is the critical determinant of its required screening coverage. By circumventing iterative cloning of PCR-amplified oligonucleotides, 3Cs multiplexing facilitates the generation of combinatorial CRISPR libraries with low distribution skews. We show that combinatorial 3Cs libraries can be screened with minimal coverages, reducing associated efforts and costs at least 10-fold. We apply a 3Cs multiplexing library targeting 12,736 autophagy gene combinations with 247,032 paired gRNAs in viability and reporter-based enrichment screens. In the viability screen, we identify, among others, the synthetic lethal WDR45B-PIK3R4 and the proliferation-enhancing ATG7-KEAP1 genetic interactions. In the reporter-based screen, we identify over 1,570 essential genetic interactions for autophagy flux, including interactions among paralogous genes, namely ATG2A-ATG2B, GABARAP-MAP1LC3B and GABARAP-GABARAPL2. However, we only observe few genetic interactions within paralogous gene families of more than two members, indicating functional compensation between them. This work establishes 3Cs multiplexing as a platform for genetic interaction screens at scale.
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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.