Advertisement

Bioinformatics Pipeline for Accurate Quantification of Fetal DNA Fraction in Maternal Plasma

  • Meng Ni
  • Xianlu Laura Peng
  • Peiyong JiangEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1909)

Abstract

The discovery of circulating cell-free fetal DNA has profoundly transformed the landscape of noninvasive prenatal testing (NIPT) and rapidly found its way into global clinical applications. The fractional concentration of cell-free fetal DNA in plasma DNA of a pregnant woman is an important parameter for understanding and interpreting analytical results of NIPT. Thus, the accurate quantification of fetal DNA fraction is indispensable when NIPT is involved. In this protocol, we describe the bioinformatics workflow to calculate fetal DNA fraction using two programs developed by our group, which provide accurate estimation.

Key words

Fetal DNA fraction Maternal plasma DNA Noninvasive prenatal testing Bioinformatics pipeline 

Notes

Acknowledgments

P.J. is currently funded by the Innovation and Technology Fund (ITS/401/17), Hong Kong.

Conflict of Interest

P.J. is a consultant to GRAIL. P.J. has filed patents/patent applications regarding cell-free DNA molecules. The remaining authors declare no conflict of interest.

References

  1. 1.
    Lo YMD, Corbetta N, Chamberlain PF et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350:485–487CrossRefGoogle Scholar
  2. 2.
    Lo YMD, Hjelm NM, Fidler C et al (1998) Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J Med 339:1734–1738CrossRefGoogle Scholar
  3. 3.
    Chiu RWK, Chan KCA, Gao Y et al (2008) Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A 105:20458–20463CrossRefGoogle Scholar
  4. 4.
    Chen EZ, Chiu RWK, Sun H et al (2011) Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One 6:1–7Google Scholar
  5. 5.
    Costa J-M, Benachi A, Gautier E (2002) New strategy for prenatal diagnosis of X-linked disorders. N Engl J Med 346:1502–1502CrossRefGoogle Scholar
  6. 6.
    Hudecova I, Jiang P, Davies J, Lo YMD, Kadir RA, Chiu RWK (2017) Noninvasive detection of F8 int22h-related inversions and sequence variants in maternal plasma of hemophilia carriers. Blood 130:340–347CrossRefGoogle Scholar
  7. 7.
    Hui WWI, Jiang P, Tong YK et al (2017) Universal haplotype-based noninvasive prenatal testing for single gene diseases. Clin Chem 63:513–524CrossRefGoogle Scholar
  8. 8.
    New MI, Tong YK, Yuen T et al (2014) Noninvasive prenatal diagnosis of congenital adrenal hyperplasia using cell-free fetal DNA in maternal plasma. J Clin Endocrinol Metab 99:E1022–E1030CrossRefGoogle Scholar
  9. 9.
    Lam KW, Jiang P, Liao GJ et al (2012) Noninvasive prenatal diagnosis of monogenic diseases by targeted massively parallel sequencing of maternal plasma: application to β-thalassemia. Clin Chem 58:1467–1475CrossRefGoogle Scholar
  10. 10.
    Allyse M, Minear MA, Berson E et al (2015) Non-invasive prenatal testing: a review of international implementation and challenges. Int J Womens Health 7:113–126CrossRefGoogle Scholar
  11. 11.
    Chandrasekharan S, Minear MA, Hung A, Allyse M (2014) Noninvasive prenatal testing goes global. Sci Transl Med 6:231fs15CrossRefGoogle Scholar
  12. 12.
    Palomaki GE, Deciu C, Kloza EM et al (2012) DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med 14:296–305CrossRefGoogle Scholar
  13. 13.
    Chiu RWKK, Akolekar R, Zheng YWLL et al (2011) Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 342:217CrossRefGoogle Scholar
  14. 14.
    Jiang P, Chan KCA, Liao GJW et al (2012) FetalQuant: deducing fractional fetal DNA concentration from massively parallel sequencing of DNA in maternal plasma. Bioinformatics 28:2883–2890CrossRefGoogle Scholar
  15. 15.
    Jiang P, Peng X, Su X et al (2016) FetalQuantSD: accurate quantification of fetal DNA fraction by shallow-depth sequencing of maternal plasma DNA. NPJ Genom Med 1:16013CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongShatinHong Kong
  2. 2.Department of Chemical PathologyThe Chinese University of Hong Kong, Prince of Wales HospitalShatinHong Kong
  3. 3.Lineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel HillUSA

Personalised recommendations