scholarly journals Cell-free DNA Fragmentation Patterns in Amniotic Fluid Identify Genetic Abnormalities and Changes due to Storage

2008 ◽  
Vol 17 (3) ◽  
pp. 185-190 ◽  
Author(s):  
Inga Peter ◽  
Hocine Tighiouart ◽  
Olav Lapaire ◽  
Kirby L. Johnson ◽  
Diana W. Bianchi ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Dna Fragmentation ◽  
Cell Free Dna ◽  
Free Dna ◽  
Genetic Abnormalities ◽  
Fragmentation Patterns

scholarly journals De novo characterization of cell-free DNA fragmentation hotspots boosts the power for early detection and localization of multi-cancer

2020 ◽  
Author(s):  
Xionghui Zhou ◽  
Yaping Liu
Keyword(s):  
Dna Fragmentation ◽  
De Novo ◽  
Early Stage ◽  
Fine Scale ◽  
Cell Free Dna ◽  
Early Stage Cancer ◽  
Free Dna ◽  
Cancer Types ◽  
Fragmentation Patterns

AbstractThe global variation of cell-free DNA fragmentation patterns is a promising biomarker for cancer diagnosis. However, the characterization of its hotspots and aberrations in early-stage cancer at the fine-scale is still poorly understood. Here, we developed an approach to de novo characterize genome-wide cell-free DNA fragmentation hotspots by integrating both fragment coverage and size from whole-genome sequencing. These hotspots are highly enriched in regulatory elements, such as promoters, and hematopoietic-specific enhancers. Surprisingly, half of the high-confident hotspots are still largely protected by the nucleosome and located near repeats, named inaccessible hotspots, which suggests the unknown origin of cell-free DNA fragmentation. In early-stage cancer, we observed the increases of fragmentation level at these inaccessible hotspots from microsatellite repeats and the decreases of fragmentation level at accessible hotspots near promoter regions, mostly with the silenced biological processes from peripheral immune cells and enriched in CTCF insulators. We identified the fragmentation hotspots from 298 cancer samples across 8 different cancer types (92% in stage I to III), 103 benign samples, and 247 healthy samples. The fine-scale fragmentation level at most variable hotspots showed cancer-specific fragmentation patterns across multiple cancer types and non-cancer controls. Therefore, with the fine-scale fragmentation signals alone in a machine learning model, we achieved 42% to 93% sensitivity at 100% specificity in different early-stage cancer. In cancer positive cases, we further localized cancer to a small number of anatomic sites with a median of 85% accuracy. The results here highlight the significance to characterize the fine-scale cell-free DNA fragmentation hotspot as a novel molecular marker for the screening of early-stage cancer that requires both high sensitivity and ultra-high specificity.

Genome-wide cell-free DNA fragmentation profiling for early cancer detection.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3018-3018
Author(s):  
Alessandro Leal ◽  
Stephen Cristiano ◽  
Jillian Phallen ◽  
Jacob Fiksel ◽  
Vilmos Adleff ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
White Blood Cells ◽  
Targeted Sequencing ◽  
Healthy Individuals ◽  
Cell Free Dna ◽  
Patients With Cancer ◽  
Molecular Features ◽  
Free Dna ◽  
Genome Wide ◽  
Fragmentation Patterns

3018 Background: Analyses of cell-free DNA (cfDNA) in the blood provide a noninvasive diagnostic avenue for patients with cancer. However, cfDNA analyses have largely focused on targeted sequencing of specific genes, and the characteristics of the origins and molecular features of cfDNA are poorly understood. We developed an ultrasensitive approach that allows simultaneous examination of a large number of abnormalities in cfDNA through genome-wide analysis of fragmentation patterns. Methods: We used a machine learning model to examined cfDNA fragmentation profiles of 236 patients with largely localized breast, colorectal, lung, ovarian, pancreatic, gastric, or bile duct cancer and 245 healthy individuals. Estimation of performance was determined by ten-fold cross validation repeated ten times. Results: cfDNA profiles of healthy individuals reflected nucleosomal patterns of white blood cells, while patients with cancer had altered fragmentation patterns. The degree of abnormality in fragmentation profiles during therapy closely matched levels of mutant allele fractions in cfDNA as determined using ultra-deep targeted sequencing. The sensitivity of detection ranged from 57% to > 99% among the seven cancer types at 98% specificity, with an overall AUC of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cfDNA analyses detected 91% of cancer patients. Conclusions: This effort is the first study to demonstrate genome-wide cell-free DNA fragmentation abnormalities in patients with cancer. Results of these analyses highlight important properties of cfDNA and provide a facile approach for screening, early detection, and monitoring of human cancer.

scholarly journals The fragmentation patterns of maternal plasma cell‐free DNA and its applications in non‐invasive prenatal testing

2020 ◽  
Vol 40 (8) ◽  
pp. 911-917 ◽  
Author(s):  
Min Pan ◽  
Pingsheng Chen ◽  
Jiafeng Lu ◽  
Zhiyu Liu ◽  
Erteng Jia ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Fragmentation Patterns

scholarly journals Larger Columns and Change of Lysis Buffer Increase the Yield of Cell-Free DNA Extracted from Amniotic Fluid

2006 ◽  
Vol 52 (1) ◽  
pp. 156-157 ◽  
Author(s):  
Olav Lapaire ◽  
Helene Stroh ◽  
Inga Peter ◽  
Janet M Cowan ◽  
Uma Tantravahi ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Cell Free Dna ◽  
Free Dna ◽  
Lysis Buffer

scholarly journals Separating the signal from the noise in metagenomic cell-free DNA sequencing

2019 ◽  
Author(s):  
Philip Burnham ◽  
Nardhy Gomez-Lopez ◽  
Michael Heyang ◽  
Alexandre Pellan Cheng ◽  
Joan Sesing Lenz ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
High Throughput Sequencing ◽  
False Positive Rate ◽  
Normal Pregnancy ◽  
True Positive Rate ◽  
Total Biomass ◽  
Metagenomic Sequencing ◽  
Cell Free Dna ◽  
Free Dna ◽  
Positive Rate

Abstract Background: Cell-free DNA (cfDNA) in blood, urine and other biofluids provides a unique window into human health. A proportion of cfDNA is derived from bacteria and viruses, creating opportunities for the diagnosis of infection via metagenomic sequencing. The total biomass of microbial-derived cfDNA in clinical isolates is low, which makes metagenomic cfDNA sequencing susceptible to contamination and alignment noise. Results: Here, we report Low Biomass Background Correction (LBBC), a bioinformatics noise filtering tool informed by the uniformity of the coverage of microbial genomes and the batch variation in the absolute abundance of microbial cfDNA. We demonstrate that LBBC leads to a dramatic reduction in false positive rate while minimally affecting the true positive rate for a cfDNA test to screen for urinary tract infection. We next performed high throughput sequencing of cfDNA in amniotic fluid collected from term uncomplicated pregnancies or those complicated with clinical chorioamnionitis with and without intra-amniotic infection. Conclusions: The data provide unique insight into the properties of fetal and maternal cfDNA in amniotic fluid, demonstrate the utility of cfDNA to screen for intra-amniotic infection, support the view that the amniotic fluid is sterile during normal pregnancy, and reveal cases of intra-amniotic inflammation without infection at term.

scholarly journals Separating the signal from the noise in metagenomic cell-free DNA sequencing

2020 ◽  
Author(s):  
Philip Burnham ◽  
Nardhy Gomez-Lopez ◽  
Michael Heyang ◽  
Alexandre Pellan Cheng ◽  
Joan Sesing Lenz ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
High Throughput Sequencing ◽  
False Positive Rate ◽  
Normal Pregnancy ◽  
True Positive Rate ◽  
Total Biomass ◽  
Metagenomic Sequencing ◽  
Cell Free Dna ◽  
Free Dna ◽  
Positive Rate

Abstract Background: Cell-free DNA (cfDNA) in blood, urine and other biofluids provides a unique window into human health. A proportion of cfDNA is derived from bacteria and viruses, creating opportunities for the diagnosis of infection via metagenomic sequencing. The total biomass of microbial-derived cfDNA in clinical isolates is low, which makes metagenomic cfDNA sequencing susceptible to contamination and alignment noise. Results: Here, we report Low Biomass Background Correction (LBBC), a bioinformatics noise filtering tool informed by the uniformity of the coverage of microbial genomes and the batch variation in the absolute abundance of microbial cfDNA. We demonstrate that LBBC leads to a dramatic reduction in false positive rate while minimally affecting the true positive rate for a cfDNA test to screen for urinary tract infection. We next performed high throughput sequencing of cfDNA in amniotic fluid collected from term uncomplicated pregnancies or those complicated with clinical chorioamnionitis with and without intra-amniotic infection. Conclusions: The data provide unique insight into the properties of fetal and maternal cfDNA in amniotic fluid, demonstrate the utility of cfDNA to screen for intra-amniotic infection, support the view that the amniotic fluid is sterile during normal pregnancy, and reveal cases of intra-amniotic inflammation without infection at term.

scholarly journals Orientation-aware plasma cell-free DNA fragmentation analysis in open chromatin regions informs tissue of origin

2019 ◽  
Vol 29 (3) ◽  
pp. 418-427 ◽  
Author(s):  
Kun Sun ◽  
Peiyong Jiang ◽  
Suk Hang Cheng ◽  
Timothy H.T. Cheng ◽  
John Wong ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Plasma Cell ◽  
Open Chromatin ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tissue Of Origin
Sign in / Sign up

Export Citation Format

Share Document