{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13(1)"],"submitter":["Ford K"],"pubmed_abstract":["Cell-cycle control is accomplished by cyclin-dependent kinases (CDKs), motivating extensive research into CDK targeting small-molecule drugs as cancer therapeutics. Here we use combinatorial CRISPR/Cas9 perturbations to uncover an extensive network of functional interdependencies among CDKs and related factors, identifying 43 synthetic-lethal and 12 synergistic interactions. We dissect CDK perturbations using single-cell RNAseq, for which we develop a novel computational framework to precisely quantify cell-cycle effects and diverse cell states orchestrated by specific CDKs. While pairwise disruption of CDK4/6 is synthetic-lethal, only CDK6 is required for normal cell-cycle progression and transcriptional activation. Multiple CDKs (CDK1/7/9/12) are synthetic-lethal in combination with PRMT"],"journal":["Scientific reports"],"pagination":["7678"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10175263"],"repository":["biostudies-literature"],"pubmed_title":["Multimodal perturbation analyses of cyclin-dependent kinases reveal a network of synthetic lethalities associated with cell-cycle regulation and transcriptional regulation."],"pmcid":["PMC10175263"],"pubmed_authors":["Ford K","Plongthongkum N","Zhang K","Chu WK","Fong SH","Meluzzi D","Tamayo P","Rainaldi J","Arunachalam V","VanArsdale T","Paul T","Jensen-Pergakes K","Mali P","Panwala R","Ideker T","Bienkowska J","Kostrowicki J","Munson BP","Kreisberg JF"],"additional_accession":[]},"is_claimable":false,"name":"Multimodal perturbation analyses of cyclin-dependent kinases reveal a network of synthetic lethalities associated with cell-cycle regulation and transcriptional regulation.","description":"Cell-cycle control is accomplished by cyclin-dependent kinases (CDKs), motivating extensive research into CDK targeting small-molecule drugs as cancer therapeutics. Here we use combinatorial CRISPR/Cas9 perturbations to uncover an extensive network of functional interdependencies among CDKs and related factors, identifying 43 synthetic-lethal and 12 synergistic interactions. We dissect CDK perturbations using single-cell RNAseq, for which we develop a novel computational framework to precisely quantify cell-cycle effects and diverse cell states orchestrated by specific CDKs. While pairwise disruption of CDK4/6 is synthetic-lethal, only CDK6 is required for normal cell-cycle progression and transcriptional activation. Multiple CDKs (CDK1/7/9/12) are synthetic-lethal in combination with PRMT","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2025-04-26T14:29:11.233Z","creation":"2025-04-06T14:34:57.399Z"},"accession":"S-EPMC10175263","cross_references":{"pubmed":["37169829"],"doi":["10.1038/s41598-023-33329-2"]}}