Abstract
BACKGROUND: Non-Invasive Prenatal Testing (NIPT) is a technique that allows pregnant women to screen for chromosomal abnormalities in their developing fetus without the need for invasive procedures like amniocentesis or chorionic villus sampling. However, current methods to detect anomaly from maternal cell-free DNAs (cfDNAs) that are based on the sequence read counts calculating z-scores face challenges with false positives and negatives. To address these challenges, we aimed to develop a novel NIPT algorithm named KF-NIPT, which is derived from the initials of k-mer and fetal fraction used in its development with the goal of significantly improving accuracy. RESULTS: We developed a KF-NIPT, a new algorithm that estimate chromosomal anomaly by calculating K-mer-based sequence depth and fetal fraction from the whole genome sequencing (WGS) data. Moreover, we implemented a modified preprocessing pipeline for the WGS data, correcting the biases of the genomic mapping quality and the GC contents. The performance of our method was evaluated using publicly available NIPT data. We could demonstrate that our method has better accuracy and sensitivity compared to those of the previous methods. CONCLUSIONS: We found that using k-mer and fetal fraction reduces errors in NIPT and have integrated this into a pipeline, showing that the traditional read count-based z-score method can be improved. KF-NIPT is implemented in the R and Python environment. The source code is available at https://github.com/eastbrain/KF-NIPT . KF-NIPT has been tested on Ubuntu Linux-64 server and Linux-64 on Windows using a WSL (Windows Subsystem for Linux).