{"doi":"10.26508/lsa.202302181","title":"A comparative study of structural variant calling in WGS from Alzheimer’s disease families","abstract":"Detecting structural variants (SVs) in whole-genome sequencing poses significant challenges. We present a protocol for variant calling, merging, genotyping, sensitivity analysis, and laboratory validation for generating a high-quality SV call set in whole-genome sequencing from the Alzheimer's Disease Sequencing Project comprising 578 individuals from 111 families. Employing two complementary pipelines, Scalpel and Parliament, for SV/indel calling, we assessed sensitivity through sample replicates (N = 9) with in silico variant spike-ins. We developed a novel metric, D-score, to evaluate caller specificity for deletions. The accuracy of deletions was evaluated by Sanger sequencing. We generated a high-quality call set of 152,301 deletions of diverse sizes. Sanger sequencing validated 114 of 146 detected deletions (78.1%). Scalpel excelled in accuracy for deletions ≤100 bp, whereas Parliament was optimal for deletions >900 bp. Overall, 83.0% and 72.5% of calls by Scalpel and Parliament were validated, respectively, including all 11 deletions called by both Parliament and Scalpel between 101 and 900 bp. Our flexible protocol successfully generated a high-quality deletion call set and a truth set of Sanger sequencing-validated deletions with precise breakpoints spanning 1-17,000 bp.","journal":"Life Science Alliance","year":2024,"id":463127,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.935,"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":227323,"name":"John J. Farrell","orcid":"0000-0001-6502-1572","position":1,"is_corresponding":false},{"id":995918,"name":"Li Charlie Xia","orcid":null,"position":2,"is_corresponding":false},{"id":455275,"name":"Beth A. Dombroski","orcid":"0000-0002-5334-1306","position":3,"is_corresponding":false},{"id":995585,"name":"Gautami Das","orcid":"0000-0001-9204-0605","position":4,"is_corresponding":false},{"id":857031,"name":"Jessica Way","orcid":null,"position":5,"is_corresponding":false},{"id":568262,"name":"Amanda B Kuzma","orcid":"0000-0002-6064-5420","position":6,"is_corresponding":false},{"id":60359,"name":"Otto Valladares","orcid":"0000-0001-8055-2187","position":7,"is_corresponding":false},{"id":568264,"name":"Yuk Yee Leung","orcid":"0000-0002-3047-5440","position":8,"is_corresponding":false},{"id":995919,"name":"Allison J. Scanlon","orcid":null,"position":9,"is_corresponding":false},{"id":55250,"name":"Irving Barrera","orcid":"0000-0001-6099-4316","position":10,"is_corresponding":false},{"id":995920,"name":"Jack Brehony","orcid":null,"position":11,"is_corresponding":false},{"id":20068,"name":"Kim C. Worley","orcid":"0000-0002-0282-1000","position":12,"is_corresponding":false},{"id":17026,"name":"Nancy R. Zhang","orcid":"0000-0002-0880-5749","position":13,"is_corresponding":false},{"id":261852,"name":"Li‐San Wang","orcid":"0000-0002-3684-0031","position":14,"is_corresponding":false},{"id":27609,"name":"Lindsay A. Farrer","orcid":"0000-0001-5533-4225","position":15,"is_corresponding":false},{"id":27607,"name":"Gerard D. Schellenberg","orcid":"0000-0003-1115-2475","position":16,"is_corresponding":false},{"id":568260,"name":"Wan‐Ping Lee","orcid":"0000-0002-5305-1181","position":17,"is_corresponding":false},{"id":63303,"name":"Badri N. Vardarajan","orcid":"0000-0002-5560-4085","position":18,"is_corresponding":false},{"id":995584,"name":"John Malamon","orcid":"0000-0002-4561-997X","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:04:28.838123Z","pmid":"38418088","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":[]}