{"doi":"10.1093/nar/gkaf678","title":"Untargeted CUT&Tag reads are enriched at accessible chromatin and restrict identification of potential G4-forming sequences in G4-targeted CUT&Tag experiments","abstract":"G-quadruplex DNA structures (G4s) form within single-stranded DNA in nucleosome-free chromatin. G4s modulate gene expression and genomic stability, so high-throughput, genome-wide mapping of G4s has generated strong research interest and methodological innovation. Recently, the Cleavage Under Targets and Tagmentation (CUT&Tag) method has been adapted to map G4s using an antibody, a nanobody, and G4-binding small molecules to target Tn5 tagmentation to G4s. These novel methods have generated high-resolution maps of G4s, but we have observed a strong colocalization between untargeted and G4-targeted CUT&Tag signal enrichment, leading us to wonder whether this colocalized signal enrichment would impact G4 mapping using these methods. We observed that the genome-wide signal distribution of untargeted CUT&Tag libraries was highly correlated with that of both cell-line-matched ATAC-seq libraries and cell-line-matched G4-mapping CUT&Tag libraries. When peaks were called from G4-mapping CUT&Tag libraries using the SEACR algorithm with inclusion of the respective matched untargeted CUT&Tag libraries, certain peaks at potential G4-forming sequences were excluded, slightly enhancing precision with which G4s are mapped while limiting recall of potential G4s. Consequently, we recommend that care be exercised when interpreting G4-targeted CUT&Tag experiments unless untargeted tagmentation is taken into account or minimized through protocol optimization.","journal":"Nucleic Acids Research","year":2025,"id":517557,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":304981,"name":"Alicia K. Byrd","orcid":"0000-0001-5484-0759","position":1,"is_corresponding":false},{"id":729593,"name":"Matthew D. Thompson","orcid":"0000-0003-1999-0385","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T02:48:59.410472Z","pmid":"40682824","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":[]}