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

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

Mokveld, T.O. (TU Delft Pattern Recognition and Bioinformatics)
Al-Ars, Z. (TU Delft Computer Engineering)
Sistermans, Erik A. (Amsterdam UMC; Vrije Universiteit Amsterdam)
Reinders, M.J.T. (TU Delft Pattern Recognition and Bioinformatics)

2023

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.

http://resolver.tudelft.nl/uuid:aa8da5a3-346f-4bad-bbd2-ad3a7672065c

https://doi.org/10.1371/journal.pone.0284493

1932-6203

PLoS ONE, 18 (4 April)

Institutional Repository

journal article

© 2023 T.O. Mokveld, Z. Al-Ars, Erik A. Sistermans, M.J.T. Reinders