{"doi":"10.1101/2025.09.25.678463","title":"EpiBlot: Joint Mapping of Chromatin Accessibility and Targeted Proteomics in HER2-expressing Breast Cancer Systems","abstract":"HER2 proteoforms promote therapeutic resistance and aggressiveness in HER2-positive breast cancer, yet their epigenetic consequences remain poorly defined. Here, we establish EpiBlot, a joint assay incorporating a customized plateATAC-seq workflow that minimizes sample inputs with single-cell western blotting to concurrently profile chromatin accessibility with protein and proteoform expression. We applied our method to engineered MCF7 cells expressing HER2 proteoforms - full-length p185HER2 or truncated 611-CTF -, where we evaluated the impact of such proteoforms on the epigenetic and protein profiles after lapatinib or doxorubicin exposure. Expression of 611-CTF elicits pervasive chromatin remodeling, whereas p185HER2 provokes only modest accessibility shifts under the same treatments. EpiBlot reveals that treatment with doxorubicin drives extensive genome-wide accessibility changes, while lapatinib treatment produces limited global effects but unmasks proteoform-specific responses. Concordance between chromatin accessibility and protein abundance is moderate, underscoring complex regulatory coupling. Extending this dual-modality approach to HER2-low patient-derived organoids uncovers distinct chromatin states and reveals a subpopulation of triple-negative breast-cancer cells expressing truncated HER2 proteoforms. We anticipate that EpiBlot will highlight the value of multimodal profiling with proteoform identification for dissecting tumor heterogeneity and therapeutic response in cancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":576077,"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":0.9406,"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":660254,"name":"Trinh Lam","orcid":"0000-0002-2274-6095","position":1,"is_corresponding":false},{"id":1328425,"name":"Nadine Goldhammer","orcid":"0000-0003-1644-3984","position":2,"is_corresponding":false},{"id":1484992,"name":"Marin Bont","orcid":"0009-0005-4789-7016","position":3,"is_corresponding":false},{"id":283437,"name":"Shruti Warhadpande","orcid":null,"position":4,"is_corresponding":false},{"id":95403,"name":"Jennifer M. Rosenbluth","orcid":"0000-0003-1314-6976","position":5,"is_corresponding":false},{"id":420688,"name":"Amy E. Herr","orcid":"0000-0002-6906-2985","position":6,"is_corresponding":false},{"id":1359741,"name":"Anna Fomitcheva Khartchenko","orcid":"0000-0002-4846-3923","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:57:56.636458Z","pmid":"41040387","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":[]}