{"doi":"10.1016/j.xgen.2022.100098","title":"CASCADE: high-throughput characterization of regulatory complex binding altered by non-coding variants","abstract":"Non-coding DNA variants (NCVs) impact gene expression by altering binding sites for regulatory complexes. New high-throughput methods are needed to characterize the impact of NCVs on regulatory complexes. We developed CASCADE (Customizable Approach to Survey Complex Assembly at DNA Elements), an array-based high-throughput method to profile cofactor (COF) recruitment. CASCADE identifies DNA-bound transcription factor-cofactor (TF-COF) complexes in nuclear extracts and quantifies the impact of NCVs on their binding. We demonstrate CASCADE sensitivity in characterizing condition-specific recruitment of COFs p300 and RBBP5 (MLL subunit) to the CXCL10 promoter in lipopolysaccharide (LPS)-stimulated human macrophages and quantify the impact of all possible NCVs. To demonstrate applicability to NCV screens, we profile TF-COF binding to ∼1,700 single-nucleotide polymorphism quantitative trait loci (SNP-QTLs) in human macrophages and identify perturbed ETS domain-containing complexes. CASCADE will facilitate high-throughput testing of molecular mechanisms of NCVs for diverse biological applications.","journal":"Cell Genomics","year":2022,"id":261762,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"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":575128,"name":"Heather Hook","orcid":null,"position":1,"is_corresponding":false},{"id":575129,"name":"Rose Zhao","orcid":null,"position":2,"is_corresponding":false},{"id":574414,"name":"Jessica L. Keenan","orcid":"0000-0001-5012-662X","position":3,"is_corresponding":false},{"id":574415,"name":"Ashley Penvose","orcid":"0000-0001-9448-9094","position":4,"is_corresponding":false},{"id":575130,"name":"Yemi Osayame","orcid":null,"position":5,"is_corresponding":false},{"id":575131,"name":"Nima Mohaghegh","orcid":null,"position":6,"is_corresponding":false},{"id":229081,"name":"Xiaoting Chen","orcid":"0000-0002-3782-3962","position":7,"is_corresponding":false},{"id":250977,"name":"Sreeja Parameswaran","orcid":"0009-0002-3631-3669","position":8,"is_corresponding":false},{"id":250976,"name":"Leah C. Kottyan","orcid":"0000-0003-3979-2220","position":9,"is_corresponding":false},{"id":19923,"name":"Matthew T. Weirauch","orcid":"0000-0001-7977-9122","position":10,"is_corresponding":false},{"id":56375,"name":"Trevor Siggers","orcid":"0000-0002-8039-7639","position":11,"is_corresponding":false},{"id":574413,"name":"David A. Bray","orcid":"0009-0008-7453-3818","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:26:16.663144Z","pmid":"35252945","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":[]}