Short tandem repeat stutter model inferred from direct measurement of in vitro stutter noise.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 03 2019
18 03 2019
Historique:
accepted:
02
01
2019
revised:
19
12
2018
received:
27
05
2018
pubmed:
31
1
2019
medline:
16
10
2019
entrez:
31
1
2019
Statut:
ppublish
Résumé
Short tandem repeats (STRs) are polymorphic genomic loci valuable for various applications such as research, diagnostics and forensics. However, their polymorphic nature also introduces noise during in vitro amplification, making them difficult to analyze. Although it is possible to overcome stutter noise by using amplification-free library preparation, such protocols are presently incompatible with single cell analysis and with targeted-enrichment protocols. To address this challenge, we have designed a method for direct measurement of in vitro noise. Using a synthetic STR sequencing library, we have calibrated a Markov model for the prediction of stutter patterns at any amplification cycle. By employing this model, we have managed to genotype accurately cases of severe amplification bias, and biallelic STR signals, and validated our model for several high-fidelity PCR enzymes. Finally, we compared this model in the context of a naïve STR genotyping strategy against the state-of-the-art on a benchmark of single cells, demonstrating superior accuracy.
Identifiants
pubmed: 30698816
pii: 5304323
doi: 10.1093/nar/gky1318
pmc: PMC6412005
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2436-2445Subventions
Organisme : European Research Council
ID : 233047
Pays : International
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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