Informative priors on fetal fraction increase power of the noninvasive prenatal screen.

Journal Article (Journal Article)

PURPOSE: Noninvasive prenatal screening (NIPS) sequences a mixture of the maternal and fetal cell-free DNA. Fetal trisomy can be detected by examining chromosomal dosages estimated from sequencing reads. The traditional method uses the Z-test, which compares a subject against a set of euploid controls, where the information of fetal fraction is not fully utilized. Here we present a Bayesian method that leverages informative priors on the fetal fraction. METHOD: Our Bayesian method combines the Z-test likelihood and informative priors of the fetal fraction, which are learned from the sex chromosomes, to compute Bayes factors. Bayesian framework can account for nongenetic risk factors through the prior odds, and our method can report individual positive/negative predictive values. RESULTS: Our Bayesian method has more power than the Z-test method. We analyzed 3,405 NIPS samples and spotted at least 9 (of 51) possible Z-test false positives. CONCLUSION: Bayesian NIPS is more powerful than the Z-test method, is able to account for nongenetic risk factors through prior odds, and can report individual positive/negative predictive values.

Full Text

Cited Authors

  • Xu, H; Wang, S; Ma, L-L; Huang, S; Liang, L; Liu, Q; Liu, Y-Y; Liu, K-D; Tan, Z-M; Ban, H; Guan, Y; Lu, Z

Published Date

  • August 2018

Published In

Volume / Issue

  • 20 / 8

Start / End Page

  • 817 - 824

PubMed ID

  • 29120459

Electronic International Standard Serial Number (EISSN)

  • 1530-0366

Digital Object Identifier (DOI)

  • 10.1038/gim.2017.186


  • eng

Conference Location

  • United States