{"doi":"10.1101/2025.10.28.685155","title":"Diploid donor-specific assembly enhances somatic structural variant detection in cancer genomes","abstract":"Somatic structural variants (SVs) play a crucial role in tumor development and evolution, yet their identification remains challenging, partly due to limitations in current reference genomes. We present a systematic evaluation of diploid donor-specific assemblies (DSAs)—generated based on hybrid long-read sequencing data—as the reference genome for detecting somatic SVs. We analyzed six tumor-normal cell line pairs, using the EchoSV tool we developed to consolidate haplotype-based SVs into a single DSA-based set and to compare SVs across reference genomes. Across Illumina, PacBio HiFi, and Oxford Nanopore Technology (ONT) data, DSA-based analysis improved read-mapping quality, identified over 20% additional SVs compared to GRCh38 and CHM13, and reduced germline artifacts. Most DSA-specific SVs were isolated deletions or insertions in repetitive elements, especially in satellite regions. By tracking sequence-context differences, we identified scenarios in which DSAs enabled detection of SVs missed on GRCh38/CHM13, and confirmed their functional impact with RNA-seq. These results highlight the value of integrating diploid DSAs into somatic SV analysis.","journal":null,"year":2025,"id":1986,"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":0.4366,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-10-29","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23350,"name":"Han Qu","orcid":"0000-0002-6016-5152","position":1,"is_corresponding":false},{"id":23351,"name":"Qian Qin","orcid":"0000-0002-2119-6263","position":2,"is_corresponding":false},{"id":30887,"name":"Alexandra P. Lewis","orcid":"0000-0002-6195-4786","position":3,"is_corresponding":false},{"id":1821,"name":"Peter J. Park","orcid":"0000-0001-9378-960X","position":4,"is_corresponding":false},{"id":23349,"name":"Yuwei Zhang","orcid":"0000-0003-4917-8056","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}