TY - JOUR
T1 - WisecondorFF
T2 - Improved Fetal Aneuploidy Detection from Shallow WGS through Fragment Length Analysis
AU - Mokveld, Tom
AU - Al-Ars, Zaid
AU - Sistermans, Erik A.
AU - Reinders, Marcel
N1 - Funding Information: This work is being funded by the Delft Data Science Center of the Delft University of Technology, which has no role in the design and execution of the study as well as the interpretation of the data and writing of the manuscript. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - In prenatal diagnostics, NIPT screening utilizing read coverage-based profiles obtained from shallow WGS data is routinely used to detect fetal CNVs. From this same data, fragment size distributions of fetal and maternal DNA fragments can be derived, which are known to be different, and often used to infer fetal fractions. We argue that the fragment size has the potential to aid in the detection of CNVs. By integrating, in parallel, fragment size and read coverage in a within-sample normalization approach, it is possible to construct a reference set encompassing both data types. This reference then allows the detection of CNVs within queried samples, utilizing both data sources. We present a new methodology, WisecondorFF, which improves sensitivity, while maintaining specificity, relative to existing approaches. WisecondorFF increases robustness of detected CNVs, and can reliably detect even at lower fetal fractions (<2%).
AB - In prenatal diagnostics, NIPT screening utilizing read coverage-based profiles obtained from shallow WGS data is routinely used to detect fetal CNVs. From this same data, fragment size distributions of fetal and maternal DNA fragments can be derived, which are known to be different, and often used to infer fetal fractions. We argue that the fragment size has the potential to aid in the detection of CNVs. By integrating, in parallel, fragment size and read coverage in a within-sample normalization approach, it is possible to construct a reference set encompassing both data types. This reference then allows the detection of CNVs within queried samples, utilizing both data sources. We present a new methodology, WisecondorFF, which improves sensitivity, while maintaining specificity, relative to existing approaches. WisecondorFF increases robustness of detected CNVs, and can reliably detect even at lower fetal fractions (<2%).
KW - Cell-free DNA
KW - Fragment size
KW - Non-invasive prenatal testing
KW - Within-sample normalization
UR - http://www.scopus.com/inward/record.url?scp=85122668376&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/diagnostics12010059
DO - https://doi.org/10.3390/diagnostics12010059
M3 - Article
C2 - 35054227
SN - 2075-4418
VL - 12
JO - Diagnostics (Basel, Switzerland)
JF - Diagnostics (Basel, Switzerland)
IS - 1
M1 - 59
ER -