A comprehensive performance analysis of sequence-based within-sample testing NIPT methods
T.O. Mokveld (TU Delft - Pattern Recognition and Bioinformatics)
Z. Al-Ars (TU Delft - Computer Engineering)
Erik A. Sistermans (Amsterdam UMC, Vrije Universiteit Amsterdam)
M.J.T. Reinders (TU Delft - Pattern Recognition and Bioinformatics)
More Info
expand_more
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
Abstract
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.
help_outline