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

Author
item XU, HANLI - Southeast University
item WANG, SHAOWEI - Beijing Hospital
item MA, LIN - Beijing Hospital
item HUANG, SHUAI - Beijing Hospital
item LIANG, LIN - Beijing Hospital
item LIU, QIAN - Beijing Usci Medical Laboratory
item LIU, YANG - Beijing Usci Medical Laboratory
item LIU, KE - Beijing Usci Medical Laboratory
item TAN, ZE - Beijing Usci Medical Laboratory
item BAN, HAO - Children'S Nutrition Research Center (CNRC)
item GUAN, YONGTAO - Children'S Nutrition Research Center (CNRC)
item LU, ZUHONG - Southeast University

Submitted to: Genetics in Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/9/2017
Publication Date: 11/9/2017
Citation: 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. 2017. Informative priors on fetal fraction increase power of the noninvasive prenatal screen. Genetics in Medicine. http://dx.doi.org/10.1038/gim.2017.186.

Interpretive Summary: During pregnancy, fetal cell free DNA can be detected in mother's peripheral blood, thus fetal aneuploidy, such as Down's Syndrome can be screened using mother's peripheral blood. Fetal fractions -- the proportion of cell free DNA that comes from fetus -- vary between pregnancies, and a small fetal fraction tend to associate with false screen results. This paper learned fetal fractions from sex chromosomes, built informative priors, and reweighed test statistics using the prior to produce a new test statistic that is more powerful and has less false results.

Technical Abstract: 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. 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. 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. 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.