TY - JOUR
T1 - Fetal fraction evaluation in non-invasive prenatal screening (NIPS)
AU - Hestand, Matthew S.
AU - Bessem, Mark
AU - van Rijn, Peter
AU - de Menezes, Renee X.
AU - Sie, Daoud
AU - Bakker, Ingrid
AU - Boon, Elles M. J.
AU - Sistermans, Erik A.
AU - Weiss, Marjan M.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - An important factor in quality control of non-invasive prenatal screening (NIPS) or testing (NIPT) is a sufficient percentage of fetal DNA to avoid false-negative results. Here we evaluate 14,379 shallow whole-genome sequenced diagnostic NIPS samples, as well as negative controls, for both technical and biological factors that can influence fetal fraction and its assessment. Technically, bioinformatics analyses can have a profound impact on fetal fraction determination. We found best performance for fetal fraction determination with the Y chromosome based tool DEFRAG for male fetuses and the count based tool SeqFF for female fetuses. Biologically, gestational age of up to 21 weeks and maternal age had no influence on fetal fraction, while an increase in weight and BMI had a negative influence on fetal fraction. While a trend was observed, no statistically significant difference in fetal fraction was found between trisomy and normal samples. Overall, these results confirm the influence of biological factors and give insight into technical factors that can affect fetal fractions in NIPS.
AB - An important factor in quality control of non-invasive prenatal screening (NIPS) or testing (NIPT) is a sufficient percentage of fetal DNA to avoid false-negative results. Here we evaluate 14,379 shallow whole-genome sequenced diagnostic NIPS samples, as well as negative controls, for both technical and biological factors that can influence fetal fraction and its assessment. Technically, bioinformatics analyses can have a profound impact on fetal fraction determination. We found best performance for fetal fraction determination with the Y chromosome based tool DEFRAG for male fetuses and the count based tool SeqFF for female fetuses. Biologically, gestational age of up to 21 weeks and maternal age had no influence on fetal fraction, while an increase in weight and BMI had a negative influence on fetal fraction. While a trend was observed, no statistically significant difference in fetal fraction was found between trisomy and normal samples. Overall, these results confirm the influence of biological factors and give insight into technical factors that can affect fetal fractions in NIPS.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85053819368&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30254213
U2 - https://doi.org/10.1038/s41431-018-0271-7
DO - https://doi.org/10.1038/s41431-018-0271-7
M3 - Article
C2 - 30254213
SN - 1018-4813
VL - 27
SP - 198
EP - 202
JO - European journal of human genetics
JF - European journal of human genetics
IS - 2
ER -