Jaroslav Budis, Juraj Gazdarica, Jan Radvanszky, Gabor Szucs, Marcel Kucharik, Lucia Strieskova, Iveta Gazdaricova, Maria Harsanyova, Frantisek Duris, Gabriel Minarik, Martina Sekelska, Balint Nagy, Jan Turna, Tomas Szemes. Combining count- and length-based z-scores leads to improved predictions innon-invasive prenatal testing. Bioinformatics, 2018. Accepted for publication.

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Download from publisher: https://doi.org/10.1093/bioinformatics/bty806

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Motivation: Non-invasive prenatal testing or NIPT is currently among the top
researched topic in obstetric care. While the performance of the current
state-of-the-art NIPT solutions achieve high sensitivity and specificity, they
still struggle with a considerable number of samples that cannot be concluded
with certainty. Such uninformative results are often subject to repeated blood
sampling and re-analysis, usually after two weeks, and this period may cause a
stress to the future mothers as well as increase the overall cost of the test.
Results: We propose a supplementary method to traditional z-scores to reduce the 
number of such uninformative calls. The method is based on a novel analysis of
the length profile of circulating cell free DNA which compares the change in such
profiles when random-based and length-based elimination of some fragments is
performed. The proposed method is not as accurate as the standard z-score;
however, our results suggest that combination of these two independent methods
correctly resolves a substantial portion of healthy samples with an uninformative
result. Additionally, we discuss how the proposed method can be used to identify 
maternal aberrations, thus reducing the risk of false positive and false negative
calls. Availability: The open-source code of the proposed methods, together with 
test data, is freely available for non-commercial users at github web page
https://github.com/jbudis/lambda. Supplementary Information: Supplementary
materials are available at Bioinformatics online.