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A comparative study of structural variant calling in WGS from Alzheimer's disease families.
Thursday,2024-04-04 11:30 America/Los_Angeles — ecterry
| Title | A comparative study of structural variant calling in WGS from Alzheimer's disease families. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Malamon, JS, Farrell, JJ, Xia, LCharlie, Dombroski, BA, Das, RG, Way, J, Kuzma, AB, Valladares, O, Leung, YYee, Scanlon, AJ, Lopez, IAntonio Ba, Brehony, J, Worley, KC, Zhang, NR, San Wang, L-, Farrer, LA, Schellenberg, GD, Lee, W-P, Vardarajan, BN |
| Journal | Life Sci Alliance |
| Volume | 7 |
| Issue | 5 |
| Date Published | 2024 May |
| ISSN | 2575-1077 |
| Keywords | Alzheimer Disease, Humans, Whole Genome Sequencing |
| Abstract | <p>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.</p> |
| DOI | 10.26508/lsa.202302181 |
| Alternate Journal | Life Sci Alliance |
| PubMed ID | 38418088 |
| PubMed Central ID | PMC10902710 |
| Grant List | HHSN268201100009I / HL / NHLBI NIH HHS / United States R01 AG054076 / AG / NIA NIH HHS / United States HHSN268201100011I / HL / NHLBI NIH HHS / United States U01 HL096902 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States RF1 AG058066 / AG / NIA NIH HHS / United States U01 AG058635 / AG / NIA NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States U01 AG058654 / AG / NIA NIH HHS / United States U01 HL096812 / HL / NHLBI NIH HHS / United States U54 AG052427 / AG / NIA NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States UF1 AG068028 / AG / NIA NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268201500001C / HL / NHLBI NIH HHS / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States U01 AG049507 / AG / NIA NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States U01 AG052411 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States RF1 AG054074 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States R01 AG049607 / AG / NIA NIH HHS / United States UF1 AG047133 / AG / NIA NIH HHS / United States U01 AG057659 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01 AG062943 / AG / NIA NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States U24 AG041689 / AG / NIA NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States U01 AG058589 / AG / NIA NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States HHSN268201500001I / HL / NHLBI NIH HHS / United States U01 AG049508 / AG / NIA NIH HHS / United States U01 AG052410 / AG / NIA NIH HHS / United States U01 HL096814 / HL / NHLBI NIH HHS / United States R01 AG033040 / AG / NIA NIH HHS / United States R01 AG048927 / AG / NIA NIH HHS / United States U54 HG003079 / HG / NHGRI NIH HHS / United States U01 AG052409 / AG / NIA NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States R01 HL070825 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States RF1 AG057519 / AG / NIA NIH HHS / United States U01 HL096899 / HL / NHLBI NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States U01 AG049506 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States |
ePub date:
24/02