A comparative study of structural variant calling in WGS from Alzheimer's disease families
© 2024 Malamon et al..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
---|---|
Enthalten in: |
Life science alliance - 7(2024), 5 vom: 28. März |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Malamon, John S [VerfasserIn] |
---|
Links: |
---|
Themen: |
---|
Anmerkungen: |
Date Completed 01.03.2024 Date Revised 02.03.2024 published: Electronic-Print Citation Status MEDLINE |
---|
doi: |
10.26508/lsa.202302181 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM369080084 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM369080084 | ||
003 | DE-627 | ||
005 | 20240302232636.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240229s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.26508/lsa.202302181 |2 doi | |
028 | 5 | 2 | |a pubmed24n1314.xml |
035 | |a (DE-627)NLM369080084 | ||
035 | |a (NLM)38418088 | ||
035 | |a (PII)e202302181 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Malamon, John S |e verfasserin |4 aut | |
245 | 1 | 2 | |a A comparative study of structural variant calling in WGS from Alzheimer's disease families |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 01.03.2024 | ||
500 | |a Date Revised 02.03.2024 | ||
500 | |a published: Electronic-Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2024 Malamon et al. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
700 | 1 | |a Farrell, John J |e verfasserin |4 aut | |
700 | 1 | |a Xia, Li Charlie |e verfasserin |4 aut | |
700 | 1 | |a Dombroski, Beth A |e verfasserin |4 aut | |
700 | 1 | |a Das, Rueben G |e verfasserin |4 aut | |
700 | 1 | |a Way, Jessica |e verfasserin |4 aut | |
700 | 1 | |a Kuzma, Amanda B |e verfasserin |4 aut | |
700 | 1 | |a Valladares, Otto |e verfasserin |4 aut | |
700 | 1 | |a Leung, Yuk Yee |e verfasserin |4 aut | |
700 | 1 | |a Scanlon, Allison J |e verfasserin |4 aut | |
700 | 1 | |a Lopez, Irving Antonio Barrera |e verfasserin |4 aut | |
700 | 1 | |a Brehony, Jack |e verfasserin |4 aut | |
700 | 1 | |a Worley, Kim C |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Nancy R |e verfasserin |4 aut | |
700 | 1 | |a Wang, Li-San |e verfasserin |4 aut | |
700 | 1 | |a Farrer, Lindsay A |e verfasserin |4 aut | |
700 | 1 | |a Schellenberg, Gerard D |e verfasserin |4 aut | |
700 | 1 | |a Lee, Wan-Ping |e verfasserin |4 aut | |
700 | 1 | |a Vardarajan, Badri N |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Life science alliance |d 2018 |g 7(2024), 5 vom: 28. März |w (DE-627)NLM286067536 |x 2575-1077 |7 nnns |
773 | 1 | 8 | |g volume:7 |g year:2024 |g number:5 |g day:28 |g month:03 |
856 | 4 | 0 | |u http://dx.doi.org/10.26508/lsa.202302181 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 7 |j 2024 |e 5 |b 28 |c 03 |