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A comprehensive performance analysis of sequence-based within-sample testing NIPT methods

BACKGROUND: Non-Invasive Prenatal Testing is often performed by utilizing read coverage-based profiles obtained from shallow whole genome sequencing to detect fetal copy number variations. Such screening typically operates on a discretized binned representation of the genome, where (ab)normality of...

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Autores principales: Mokveld, Tom, Al-Ars, Zaid, Sistermans, Erik A., Reinders, Marcel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104307/
https://www.ncbi.nlm.nih.gov/pubmed/37058455
http://dx.doi.org/10.1371/journal.pone.0284493
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author Mokveld, Tom
Al-Ars, Zaid
Sistermans, Erik A.
Reinders, Marcel
author_facet Mokveld, Tom
Al-Ars, Zaid
Sistermans, Erik A.
Reinders, Marcel
author_sort Mokveld, Tom
collection PubMed
description BACKGROUND: Non-Invasive Prenatal Testing is often performed by utilizing read coverage-based profiles obtained from shallow whole genome sequencing to detect fetal copy number variations. Such screening typically operates on a discretized binned representation of the genome, where (ab)normality of bins of a set size is judged relative to a reference panel of healthy samples. In practice such approaches are too costly given that for each tested sample they require the resequencing of the reference panel to avoid technical bias. Within-sample testing methods utilize the observation that bins on one chromosome can be judged relative to the behavior of similarly behaving bins on other chromosomes, allowing the bins of a sample to be compared among themselves, avoiding technical bias. RESULTS: We present a comprehensive performance analysis of the within-sample testing method Wisecondor and its variants, using both experimental and simulated data. We introduced alterations to Wisecondor to explicitly address and exploit paired-end sequencing data. Wisecondor was found to yield the most stable results across different bin size scales while producing more robust calls by assigning higher Z-scores at all fetal fraction ranges. CONCLUSIONS: Our findings show that the most recent available version of Wisecondor performs best.
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spelling pubmed-101043072023-04-15 A comprehensive performance analysis of sequence-based within-sample testing NIPT methods Mokveld, Tom Al-Ars, Zaid Sistermans, Erik A. Reinders, Marcel PLoS One Research Article BACKGROUND: Non-Invasive Prenatal Testing is often performed by utilizing read coverage-based profiles obtained from shallow whole genome sequencing to detect fetal copy number variations. Such screening typically operates on a discretized binned representation of the genome, where (ab)normality of bins of a set size is judged relative to a reference panel of healthy samples. In practice such approaches are too costly given that for each tested sample they require the resequencing of the reference panel to avoid technical bias. Within-sample testing methods utilize the observation that bins on one chromosome can be judged relative to the behavior of similarly behaving bins on other chromosomes, allowing the bins of a sample to be compared among themselves, avoiding technical bias. RESULTS: We present a comprehensive performance analysis of the within-sample testing method Wisecondor and its variants, using both experimental and simulated data. We introduced alterations to Wisecondor to explicitly address and exploit paired-end sequencing data. Wisecondor was found to yield the most stable results across different bin size scales while producing more robust calls by assigning higher Z-scores at all fetal fraction ranges. CONCLUSIONS: Our findings show that the most recent available version of Wisecondor performs best. Public Library of Science 2023-04-14 /pmc/articles/PMC10104307/ /pubmed/37058455 http://dx.doi.org/10.1371/journal.pone.0284493 Text en © 2023 Mokveld et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mokveld, Tom
Al-Ars, Zaid
Sistermans, Erik A.
Reinders, Marcel
A comprehensive performance analysis of sequence-based within-sample testing NIPT methods
title A comprehensive performance analysis of sequence-based within-sample testing NIPT methods
title_full A comprehensive performance analysis of sequence-based within-sample testing NIPT methods
title_fullStr A comprehensive performance analysis of sequence-based within-sample testing NIPT methods
title_full_unstemmed A comprehensive performance analysis of sequence-based within-sample testing NIPT methods
title_short A comprehensive performance analysis of sequence-based within-sample testing NIPT methods
title_sort comprehensive performance analysis of sequence-based within-sample testing nipt methods
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104307/
https://www.ncbi.nlm.nih.gov/pubmed/37058455
http://dx.doi.org/10.1371/journal.pone.0284493
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