{"doi":"10.1038/s41592-021-01248-7","title":"Systematic evaluation of chromosome conformation capture assays","abstract":"Chromosome conformation capture (3C) assays are used to map chromatin interactions genome-wide. Chromatin interaction maps provide insights into the spatial organization of chromosomes and the mechanisms by which they fold. Hi-C and Micro-C are widely used 3C protocols that differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of 3C experimental parameters. We identified optimal protocol variants for either loop or compartment detection, optimizing fragment size and cross-linking chemistry. We used this knowledge to develop a greatly improved Hi-C protocol (Hi-C 3.0) that can detect both loops and compartments relatively effectively. In addition to providing benchmarked protocols, this work produced ultra-deep chromatin interaction maps using Micro-C, conventional Hi-C and Hi-C 3.0 for key cell lines used by the 4D Nucleome project.","journal":"Nature Methods","year":2021,"id":146013,"datarank":4.797746816173107,"base_score":5.616771097666572,"endowment":5.616771097666572,"self_citation_contribution":0.8425156646499858,"citation_network_contribution":3.955231151523121,"self_endowment_contribution":0.8425156646499858,"citer_contribution":3.955231151523121,"corpus_percentile":null,"corpus_rank":null,"citation_count":274,"citer_count":200,"citers_with_citation_signal":161,"citers_with_endowment":161,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109519,"name":"Liyan Yang","orcid":"0000-0002-3421-9866","position":1,"is_corresponding":false},{"id":109514,"name":"Sameer Abraham","orcid":"0000-0002-7460-2771","position":2,"is_corresponding":false},{"id":109515,"name":"Sergey V. Venev","orcid":"0000-0002-1507-7460","position":3,"is_corresponding":false},{"id":68355,"name":"Nils Krietenstein","orcid":"0000-0003-2519-6305","position":4,"is_corresponding":false},{"id":109518,"name":"Krishna Mohan Parsi","orcid":"0000-0002-6002-3816","position":5,"is_corresponding":false},{"id":43271,"name":"Hakan Özadam","orcid":"0000-0001-6571-1661","position":6,"is_corresponding":false},{"id":348429,"name":"Marlies E. Oomen","orcid":"0000-0002-2432-3862","position":7,"is_corresponding":false},{"id":620394,"name":"Ankita Nand","orcid":"0000-0001-7071-5114","position":8,"is_corresponding":false},{"id":289399,"name":"Hui Mao","orcid":"0000-0002-0147-6022","position":9,"is_corresponding":false},{"id":56351,"name":"Ryan M. Genga","orcid":null,"position":10,"is_corresponding":false},{"id":56350,"name":"Rene Maehr","orcid":"0000-0002-9520-3382","position":11,"is_corresponding":false},{"id":37164,"name":"Oliver J. Rando","orcid":"0000-0003-1516-9397","position":12,"is_corresponding":false},{"id":109520,"name":"Leonid A. Mirny","orcid":"0000-0002-0785-5410","position":13,"is_corresponding":false},{"id":109517,"name":"Johan H. Gibcus","orcid":"0000-0002-0851-7560","position":14,"is_corresponding":false},{"id":11679,"name":"Job Dekker","orcid":"0000-0001-5631-0698","position":15,"is_corresponding":false},{"id":479622,"name":"Betül Akgöl Oksuz","orcid":"0000-0002-0177-4193","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:18.947086Z","pmid":"34480151","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":[]}