PT  - JOURNAL ARTICLE
AU  - Carlo G. Artieri
AU  - Carrie Haverty
AU  - Eric A. Evans
AU  - James D. Goldberg
AU  - Imran S. Haque
AU  - Yuval Yaron
AU  - Dale Muzzey
TI  - Noninvasive Prenatal Screening at Low Fetal Fraction: Comparing Whole-Genome Sequencing and Single-Nucleotide Polymorphism Methods
AID  - 10.1101/096024
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 096024
4099  - http://biorxiv.org/content/early/2016/12/21/096024.short
4100  - http://biorxiv.org/content/early/2016/12/21/096024.full
AB  - Objective Performance of noninvasive prenatal screening (NIPS) methodologies when applied to low fetal fraction samples is not well established. The single-nucleotide polymorphism (SNP) method fails samples below a predetermined fetal fraction threshold, whereas some laboratories employing the whole-genome sequencing (WGS) method report aneuploidy calls for all samples. Here, the performance of the two methods was compared to determine which approach actually detects more fetal aneuploidies.Methods Computational models were parameterized with up-to-date published data and used to compare the performance of the two methods at calling common fetal trisomies (T21, T18, T13) at low fetal fractions. Furthermore, clinical experience data were reviewed to determine aneuploidy detection rates based on compliance with recent invasive screening recommendations.Results The SNP method’s performance is dependent on the origin of the trisomy, and is lowest for the most common trisomies (maternal M1 nondisjunction). Consequently, the SNP method cannot maintain acceptable performance at fetal fractions below ~3%. In contrast, the WGS method maintains high specificity independent of fetal fraction and has >80% sensitivity for trisomies in low fetal fraction samples.Conclusion The WGS method will detect more aneuploidies below the fetal fraction threshold at which many labs issue a no-call result, avoiding unnecessary invasive procedures.