GenomomFF: Cost-Effective Method to Measure Fetal Fraction by Adaptive Multiple Regression Techniques With Optimally Selected Autosomal Chromosome Regions

Sunshin Kim,Young Joo Jeon,Kangseok Kim

doi:10.1109/access.2020.3000483

Sunshin Kim, Young Joo Jeon + Show 1 more

Open Access

https://doi.org/10.1109/access.2020.3000483

Copy DOI

Abstract

The accurate measure of fetal fraction is important to ensure the results of noninvasive prenatal testing. However, measuring fetal fraction could require a substantial amount of data and additional costs. Therefore, this study proposes an alternative method of measuring fetal fraction with a limited sample size and low sequencing reads. Adaptive machine-learning algorithms customized to each laboratory’s environment, were used to measure fetal fraction. Pregnant women with female fetuses were tested to exclude the bias caused by training data of women carrying male fetuses. The accuracy of fetal DNA fraction prediction was enhanced by increasing the training sample size. When trained with 1,000 samples (males) and tested with 45 samples (females), the optimal bin sizes using the read count and size features were 300 kb and 800 kb, respectively. Comparing the new 300-kb bin to the 50-kb bin used by SeqFF with 4,000–5,000 training samples, the correlation was approximately 3-5% higher with the 300-kb bin. Therefore, we propose an effective and tailored method to measure fetal fraction in individual laboratories with limited sample collecting conditions and relatively low-coverage sequencing data.

Highlights

The presence of cell-free DNA of fetal origin in the plasma of pregnant women [1] led to the concept of noninvasive prenatal testing (NIPT) and, eventually, the development of a technique to diagnose fetal chromosomal aneuploidy [2], [3]
SeqFF is a software that enables the computation of fetal fraction by entering the read-count ratio obtained in 50-kb bins using parameters computed based on training data with a sample size of 25,312
The correlation between the Y-chromosome-based standard fetal fraction and the fetal fraction measured using SeqFF was calculated for test sample sizes ranging from 100 to 500

Summary

Introduction

The presence of cell-free DNA (cfDNA) of fetal origin in the plasma of pregnant women [1] led to the concept of noninvasive prenatal testing (NIPT) and, eventually, the development of a technique to diagnose fetal chromosomal aneuploidy [2], [3]. Both the mother and fetus in the plasma of the pregnant woman. The simplest and standard method of measuring fetal fraction is determination of the read ratio of the Y chromosome [9]–[11], but this method is only suitable for male fetuses. Another method of measuring fetal DNA fraction is a single-nucleotide polymorphism (SNP)-based platform that can be used on either sex [5], [6], [8], [12]–[14]. Alternative methods of measuring fetal fraction using SNP imputation have been developed [15]

Methods

Results

Discussion

Conclusion