{"doi":"10.1101/2020.07.15.202929","title":"Sensitive alignment using paralogous sequence variants improves long read mapping and variant calling in segmental duplications","abstract":"Abstract The ability to characterize repetitive regions of the human genome is limited by the read lengths of short-read sequencing technologies. Although long-read sequencing technologies such as Pacific Biosciences and Oxford Nanopore can potentially overcome this limitation, long segmental duplications with high sequence identity pose challenges for long-read mapping. We describe a probabilistic method, DuploMap, designed to improve the accuracy of long read mapping in segmental duplications. It analyzes reads mapped to segmental duplications using existing long-read aligners and leverages paralogous sequence variants (PSVs) – sequence differences between paralogous sequences – to distinguish between multiple alignment locations. On simulated datasets, Duplomap increased the percentage of correctly mapped reads with high confidence for multiple long-read aligners including Minimap2 (74.3% to 90.6%) and BLASR (82.9% to 90.7%) while maintaining high precision. Across multiple whole-genome long-read datasets, DuploMap aligned an additional 8-21% of the reads in segmental duplications with high confidence relative to Minimap2. Using Duplomap aligned PacBio CCS reads, an additional 8.9 Mbp of DNA sequence was mappable, variant calling achieved a higher F1-score and 14,713 additional variants supported by linked-read data were identified. Finally, we demonstrate that a significant fraction of PSVs in segmental duplications overlap with variants and adversely impact short-read variant calling.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123885,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":280978,"name":"Vikas Bansal","orcid":"0000-0002-6684-5335","position":1,"is_corresponding":false},{"id":19699,"name":"Timofey Prodanov","orcid":"0000-0001-7469-6651","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","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":[]}