GenomeMixer and TRUST: Novel bioinformatics tools to improve reliability of Non-Invasive Prenatal Testing (NIPT) for fetal aneuploidies.
Aneuploidy detection
Confidence intervals
Fetal fraction
Non-invasive prenatal testing
Semi-supervised method
Journal
Computational and structural biotechnology journal
ISSN: 2001-0370
Titre abrégé: Comput Struct Biotechnol J
Pays: Netherlands
ID NLM: 101585369
Informations de publication
Date de publication:
2022
2022
Historique:
received:
22
09
2021
revised:
27
01
2022
accepted:
17
02
2022
entrez:
4
3
2022
pubmed:
5
3
2022
medline:
5
3
2022
Statut:
epublish
Résumé
Non-invasive prenatal testing (NIPT) screens for common fetal chromosomal abnormalities through analysis of circulating cell-free DNA in maternal blood by massive parallel sequencing. NIPT reliability relies on both the estimation of the fetal fraction (ff) and on the sequencing depth (sd) but how these parameters are linked is unknown. Several bioinformatics tools have been developed to determine the ff but there is no universal ff threshold applicable across diagnostics laboratories. Thus, we developed two tools allowing the implementation of a strategy for NIPT results validation in clinical practice: GenomeMixer, a semi-supervised approach to create synthetic sequences and to estimate confidence intervals for NIPT validation and TRUST to estimate the reliability of NIPT results based on confidence intervals found in this study. We retrospectively validated these new tools on 2 cohorts for a total of 1439 samples with 31 confirmed aneuploidies. Through the analysis of the interrelationship between ff, sd and chromosomal aberration detection, we demonstrate that these parameters are profoundly connected and cannot be considered independently. Our tools take in account this critical relationship to improve NIPT reliability and facilitate cross laboratory standardization of this screening test.
Identifiants
pubmed: 35242293
doi: 10.1016/j.csbj.2022.02.014
pii: S2001-0370(22)00054-X
pmc: PMC8881690
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1028-1035Informations de copyright
© 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests
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