{"doi":"10.1101/gr.277334.122","title":"Gaps and complex structurally variant loci in phased genome assemblies","abstract":"There has been tremendous progress in phased genome assembly production by combining long-read data with parental information or linked-read data. Nevertheless, a typical phased genome assembly generated by trio-hifiasm still generates more than 140 gaps. We perform a detailed analysis of gaps, assembly breaks, and misorientations from 182 haploid assemblies obtained from a diversity panel of 77 unique human samples. Although trio-based approaches using HiFi are the current gold standard, chromosome-wide phasing accuracy is comparable when using Strand-seq instead of parental data. Importantly, the majority of assembly gaps cluster near the largest and most identical repeats (including segmental duplications [35.4%], satellite DNA [22.3%], or regions enriched in GA/AT-rich DNA [27.4%]). Consequently, 1513 protein-coding genes overlap assembly gaps in at least one haplotype, and 231 are recurrently disrupted or missing from five or more haplotypes. Furthermore, we estimate that 6-7 Mbp of DNA are misorientated per haplotype irrespective of whether trio-free or trio-based approaches are used. Of these misorientations, 81% correspond to bona fide large inversion polymorphisms in the human species, most of which are flanked by large segmental duplications. We also identify large-scale alignment discontinuities consistent with 11.9 Mbp of deletions and 161.4 Mbp of insertions per haploid genome. Although 99% of this variation corresponds to satellite DNA, we identify 230 regions of euchromatic DNA with frequent expansions and contractions, nearly half of which overlap with 197 protein-coding genes. Such variable and incompletely assembled regions are important targets for future algorithmic development and pangenome representation.","journal":"Genome Research","year":2023,"id":389374,"datarank":0.62147020895873,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":0.0,"self_endowment_contribution":0.62147020895873,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":24561,"name":"Mitchell R. Vollger","orcid":"0000-0002-8651-1615","position":1,"is_corresponding":false},{"id":19702,"name":"William T. Harvey","orcid":"0000-0003-0646-7528","position":2,"is_corresponding":false},{"id":55037,"name":"Allison N. Rozanski","orcid":"0000-0002-5034-1773","position":3,"is_corresponding":false},{"id":19693,"name":"Peter Ebert","orcid":"0000-0001-7441-532X","position":4,"is_corresponding":false},{"id":6314,"name":"Hickey, Glenn","orcid":"0000-0002-2280-9404","position":5,"is_corresponding":false},{"id":19715,"name":"Patrick Hasenfeld","orcid":"0000-0003-2319-2482","position":6,"is_corresponding":false},{"id":30904,"name":"Ashley D. Sanders","orcid":"0000-0003-3945-0677","position":7,"is_corresponding":false},{"id":92308,"name":"Catherine Brasseur","orcid":"0000-0002-9481-013X","position":8,"is_corresponding":false},{"id":108507,"name":"Jan O. Korbel","orcid":"0000-0002-2798-3794","position":9,"is_corresponding":false},{"id":108063,"name":"Benedict Paten","orcid":"0000-0001-8863-3539","position":10,"is_corresponding":false},{"id":6321,"name":"Tobias Marschall","orcid":"0000-0002-9376-1030","position":11,"is_corresponding":false},{"id":2125,"name":"Evan E. Eichler","orcid":"0000-0002-8246-4014","position":12,"is_corresponding":false},{"id":19696,"name":"David Porubsky","orcid":"0000-0001-8414-8966","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:22.323414Z","pmid":"37164484","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":[]}