{"doi":"10.1101/2024.04.02.24305233","title":"Concordance of whole-genome long-read sequencing with standard clinical testing for Prader-Willi and Angelman syndromes","abstract":"Abstract Current clinical testing approaches for individuals with suspected imprinting disorders are complex, often requiring multiple tests performed in a stepwise fashion to make a precise molecular diagnosis. We investigated whether whole-genome long-read sequencing (LRS) could be used as a single data source to simultaneously evaluate copy number variants (CNVs), single nucleotide variants (SNVs), structural variants (SVs), and differences in methylation in a cohort of individuals known to have either Prader-Willi or Angelman syndrome. We evaluated 25 individuals sequenced to an average depth of coverage of 36x on an Oxford Nanopore PromethION. A custom one-page report was generated that could be used to assess copy number, SNVs, and methylation patterns at select CpG sites within the 15q11.2-q13.1 region and prioritize candidate pathogenic variants in UBE3A . After training with three positive controls, three analysts blinded to the known clinical diagnosis arrived at the correct molecular diagnosis for 22 out of 22 cases (20 true positive, 2 negative controls). Our findings demonstrate the utility of LRS as a single, comprehensive data source for complex clinical testing, offering potential benefits such as reduced testing costs, increased diagnostic yield, and shorter turnaround times in the clinical laboratory.","journal":"medRxiv","year":2024,"id":490560,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9348,"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":492789,"name":"Miranda Galey","orcid":"0000-0002-4721-7499","position":1,"is_corresponding":false},{"id":308533,"name":"Anita E. Beck","orcid":"0000-0002-7965-0326","position":2,"is_corresponding":false},{"id":243282,"name":"Madelyn A. Gillentine","orcid":"0000-0002-8989-2214","position":3,"is_corresponding":false},{"id":1336154,"name":"Jaya Narayanan","orcid":null,"position":4,"is_corresponding":false},{"id":1235122,"name":"Nikhita Damaraju","orcid":"0000-0001-5054-037X","position":5,"is_corresponding":false},{"id":790670,"name":"Joy Goffena","orcid":"0000-0002-2346-2879","position":6,"is_corresponding":false},{"id":1324904,"name":"Sophie Storz","orcid":"0009-0001-3099-9738","position":7,"is_corresponding":false},{"id":24426,"name":"Danny E. Miller","orcid":"0000-0001-6096-8601","position":8,"is_corresponding":false},{"id":822538,"name":"Cate Paschal","orcid":"0000-0002-9400-5560","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:08:37.162700Z","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":[]}