Elsevier

Genetics in Medicine

Volume 20, Issue 8, August 2018, Pages 817-824
Genetics in Medicine

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

https://doi.org/10.1038/gim.2017.186Get rights and content
Under a Creative Commons license
open access

Abstract

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.

Keywords

Bayes factor
fetal fraction
noninvasive
prenatal
informative prior

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