{"doi":"10.1101/2024.07.28.605011","title":"Determining mesoscale chromatin structure parameters from spatially correlated cleavage data using a coarse-grained oligonucleosome model","abstract":"The three-dimensional structure of chromatin has emerged as an important feature of eukaryotic gene regulation. Recent technological advances in DNA sequencing-based assays have revealed locus- and chromatin state-specific structural patterns at the length scale of a few nucleosomes (~1 kb). However, interpreting these data sets remains challenging. Radiation-induced correlated cleavage of chromatin (RICC-seq) is one such chromatin structure assay that maps DNA-DNA-contacts at base pair resolution by sequencing single-stranded DNA fragments released from irradiated cells. Here, we develop a flexible modeling and simulation framework to enable the interpretation of RICC-seq data in terms of oligonucleosome structure ensembles. Nucleosomes are modeled as rigid bodies with excluded volume and adjustable DNA wrapping, connected by linker DNA modeled as a worm-like chain. We validate the model's parameters against cryo-electron microscopy and sedimentation data. Our results show that RICC-seq is sensitive to nucleosome spacing, nucleosomal DNA wrapping, and the strength of inter-nucleosome interactions. We show that nucleosome repeat lengths consistent with orthogonal assays can be extracted from experimental RICC-seq data using a 1D convolutional neural net trained on RICC-seq signal predicted from simulated ensembles. We thus provide a suite of analysis tools that add quantitative structural interpretability to RICC-seq experiments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491530,"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":0.9312,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1248912,"name":"Nicole Pagane","orcid":"0009-0007-0079-0515","position":1,"is_corresponding":false},{"id":1337481,"name":"D. West","orcid":null,"position":2,"is_corresponding":false},{"id":554763,"name":"Andrew J. Spakowitz","orcid":"0000-0002-0585-1942","position":3,"is_corresponding":false},{"id":555523,"name":"Viviana I. Risca","orcid":"0000-0003-2670-8704","position":4,"is_corresponding":false},{"id":1337125,"name":"Ariana Brenner Clerkin","orcid":"0000-0003-0911-6619","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:08:45.247225Z","pmid":"39131347","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":[]}