ArticleProceedings of the National Academy of Sciences of the United States of America2016
Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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101 citing papers in PubMed, 192 citations in OpenAlex.
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- Holistic determination of ends of cfDNA molecules.Cell genomics · 2026Article
- Cell-free DNA fragmentomes for noninvasive detection of liver cirrhosis and other diseases.Science translational medicine · 2026Article
- A polygenic growth score and risk for large for gestational age birth weight.Journal of the Endocrine Society · 2026Article
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- High-quality Population-specific Haplotype-resolved Reference Panel in the Genomic and Pangenomic Eras.Genomics, proteomics & bioinformatics · 2025Review
- Fetal Polygenic Growth Score and Risk for Large for Gestational Age Birth Weight in Nulliparas: Secondary Analysis of a Prospective Cohort Study.medRxiv : the preprint server for health sciences · 2025Article
- Circulating Cell-free DNA Fragmentomics Detection and Beyond.Aging and disease · 2025Review
- Liquid Biopsy in B and T Cell Lymphomas: From Bench to Bedside.International journal of molecular sciences · 2025Review
- DAGIP: alleviating cell-free DNA sequencing biases with optimal transport.Genome biology · 2025Article
- Liquid Biopsy in Neuropsychiatric Disorders: A Step Closer to Precision Medicine.Molecular neurobiology · 2025Review
- Unravelling the Significance of Extracellular Vesicle-Associated DNA in Cancer Biology and Its Potential Clinical Applications.Journal of extracellular vesicles · 2025Review
- Application of plasma cell-free DNA in screening of advanced colorectal adenoma.European journal of medical research · 2025Review
- Artificial intelligence and machine learning in cell-free-DNA-based diagnostics.Genome research · 2025Review
- Cell-free placental DNA: What do we really know?PLoS genetics · 2024Review
- Noninvasive fetal genotyping using deep neural networks.Briefings in bioinformatics · 2024Article
- Cell-free nucleic acid fragmentomics: A non-invasive window into cellular epigenomes.Translational oncology · 2024Review
- Cell-free DNA end characteristics enable accurate and sensitive cancer diagnosis.Cell reports methods · 2024Article
41 more citing papers are in PubMed but not listed here.
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11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasma DNA obtained from a pregnant woman was sequenced to a depth of 270× haploid genome coverage. Comparing the maternal plasma DNA sequencing data with the parental genomic DNA data and using a series of bioinformatics filters, fetal de novo mutations were detected at a sensitivity of 85% and a positive predictive value of 74%. These results represent a 169-fold improvement in the positive predictive value over previous attempts. Improvements in the interpretation of the sequence information of every base position in the genome allowed us to interrogate the maternal inheritance of the fetus for 618,271 of 656,676 (94.2%) heterozygous SNPs within the maternal genome. The fetal genotype at each of these sites was deduced individually, unlike previously, where the inheritance was determined for a collection of sites within a haplotype. These results represent a 90-fold enhancement in the resolution in determining the fetus's maternal inheritance. Selected genomic locations were more likely to be found at the ends of plasma DNA molecules. We found that a subset of such preferred ends exhibited selectivity for fetal- or maternal-derived DNA in maternal plasma. The ratio of the number of maternal plasma DNA molecules with fetal preferred ends to those with maternal preferred ends showed a correlation with the fetal DNA fraction. Finally, this second generation approach for noninvasive fetal whole-genome analysis was validated in a pregnancy diagnosed with cardiofaciocutaneous syndrome with maternal plasma DNA sequenced to 195× coverage. The causative de novo BRAF mutation was successfully detected through the maternal plasma DNA analysis.
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