{"doi":"10.1101/2022.05.31.494230","title":"Achieving single nucleotide sensitivity in direct hybridization genome imaging","abstract":"Abstract Direct visualization of point mutations in situ can be informative for studying genetic diseases and nuclear biology. We describe a direct hybridization genome imaging method with single-nucleotide sensitivity, sgGOLDFISH, which leverages the high cleavage specificity of enhanced Cas9 combined with a single extended guide RNA to load a superhelicase and reveal probe binding sites through local denaturation. Using sgGOLDFISH, we identified base-editor-modified and unmodified progeroid fibroblasts from a heterogeneous population, validated the identification through progerin immunofluorescence, and demonstrated accurate sub-nuclear localization of point mutations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303429,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":688245,"name":"Wayne Taylor Cottle","orcid":"0000-0002-3024-5848","position":1,"is_corresponding":false},{"id":467229,"name":"Haobo Wang","orcid":"0000-0002-3606-5282","position":2,"is_corresponding":false},{"id":475675,"name":"Momčilo Gavrilov","orcid":"0000-0002-5816-3406","position":3,"is_corresponding":false},{"id":656706,"name":"Roger S. Zou","orcid":"0000-0003-1338-6398","position":4,"is_corresponding":false},{"id":459162,"name":"Scott Bailey","orcid":"0000-0003-1953-7089","position":5,"is_corresponding":false},{"id":22168,"name":"Taekjip Ha","orcid":"0000-0003-2195-6258","position":6,"is_corresponding":false},{"id":255699,"name":"Yanbo Wang","orcid":"0000-0001-7329-4386","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","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":[]}