{"doi":"10.1101/2021.08.06.455336","title":"An Isogenic Cell Line Panel for Sequence-based Screening of Targeted Anti-cancer Drugs","abstract":"Summary We describe the creation and characterization of an isogenic cell line panel representing common cancer pathways, with multiple features optimized for high-throughput screening. More than 1,800 cell lines from three normal human cells were generated using CRISPR-technologies. Surprisingly, we discovered most of these lines did not result in complete gene inactivation, despite integration of sgRNA at the desired genomic site. However, a subset of the lines harbored true, biallelic disruptions of the targeted tumor suppressor gene, yielding a final panel of 100 well-characterize lines covering 19 pathways frequently subject to loss of function in cancers. This panel included genetic markers optimized for sequence-based ratiometric assays for drug-based screening assays. To illustrate the potential utility of this panel, we developed a multiplexed high-throughput screen that identified Wee1 inhibitor MK-1775 as a selective growth inhibitor of cells with inactivation of TP53 . These cell lines and screening approach should prove useful for researchers studying a variety of cellular and biochemical phenomena.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226137,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5414,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":732242,"name":"Nicolas Wyhs","orcid":"0000-0003-4252-4470","position":1,"is_corresponding":false},{"id":658685,"name":"Surojit Sur","orcid":"0000-0003-4536-7343","position":2,"is_corresponding":false},{"id":829654,"name":"Blair Ptak","orcid":null,"position":3,"is_corresponding":false},{"id":275560,"name":"Maria Popoli","orcid":"0000-0003-2151-7749","position":4,"is_corresponding":false},{"id":829655,"name":"Laura Dobbyn","orcid":null,"position":5,"is_corresponding":false},{"id":829656,"name":"Tasos Papadopoulos","orcid":null,"position":6,"is_corresponding":false},{"id":24634,"name":"Chetan Bettegowda","orcid":"0000-0001-9991-7123","position":7,"is_corresponding":false},{"id":2254,"name":"Nickolas Papadopoulos","orcid":"0000-0001-7135-7451","position":8,"is_corresponding":false},{"id":2255,"name":"Bert Vogelstein","orcid":"0000-0003-0766-3854","position":9,"is_corresponding":false},{"id":62904,"name":"Shibin Zhou","orcid":"0000-0003-1941-4425","position":10,"is_corresponding":false},{"id":2256,"name":"Kenneth W. Kinzler","orcid":"0000-0001-5591-1176","position":11,"is_corresponding":false},{"id":829136,"name":"Ashley L. Cook","orcid":"0000-0001-6789-5732","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}