Article ; Online: A comparative study of structural variant calling in WGS from Alzheimer's disease families.
Life science alliance
2024 Volume 7, Issue 5
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 ... ...
| 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. |
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| MeSH term(s) | Humans ; Alzheimer Disease/genetics ; Whole Genome Sequencing/methods |
| Language | English |
| Publishing date | 2024-02-28 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2575-1077 |
| ISSN (online) | 2575-1077 |
| DOI | 10.26508/lsa.202302181 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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