scholarly journals At the dawn: cell-free DNA fragmentomics and gene regulation

2021 ◽  
Author(s):  
Yaping Liu
Keyword(s):  
Gene Regulation ◽  
Peripheral Blood ◽  
Cell Free Dna ◽  
The Road ◽  
Free Dna ◽  
Experimental Approaches ◽  
Fragmentation Patterns ◽  
Peripheral Immune Cells ◽  
Molecular Layers

AbstractEpigenetic mechanisms play instrumental roles in gene regulation during embryonic development and disease progression. However, it is challenging to non-invasively monitor the dynamics of epigenomes and related gene regulation at inaccessible human tissues, such as tumours, fetuses and transplanted organs. Circulating cell-free DNA (cfDNA) in peripheral blood provides a promising opportunity to non-invasively monitor the genomes from these inaccessible tissues. The fragmentation patterns of plasma cfDNA are unevenly distributed in the genome and reflect the in vivo gene-regulation status across multiple molecular layers, such as nucleosome positioning and gene expression. In this review, we revisited the computational and experimental approaches that have been recently developed to measure the cfDNA fragmentomics across different resolutions comprehensively. Moreover, cfDNA in peripheral blood is released following cell death, after apoptosis or necrosis, mainly from haematopoietic cells in healthy people and diseased tissues in patients. Several cfDNA-fragmentomics approaches showed the potential to identify the tissues-of-origin in cfDNA from cancer patients and healthy individuals. Overall, these studies paved the road for cfDNA fragmentomics to non-invasively monitor the in vivo gene-regulatory dynamics in both peripheral immune cells and diseased tissues.

scholarly journals Short-Term Treadmill Running as a Model for Studying Cell-Free DNA Kinetics In Vivo

2011 ◽  
Vol 57 (4) ◽  
pp. 633-636 ◽  
Author(s):  
Thomas Beiter ◽  
Annunziata Fragasso ◽  
Jens Hudemann ◽  
Andreas M Nieß ◽  
Perikles Simon
Keyword(s):  
Time Course ◽  
Treadmill Exercise ◽  
Plasma Concentrations ◽  
High Mobility ◽  
Treadmill Running ◽  
Short Term ◽  
Cell Free Dna ◽  
Free Dna ◽  
Cross Country

BACKGROUND Increased plasma concentrations of cell-free DNA (cf-DNA) are considered a hallmark of various clinical conditions. Despite intensive research in this field, limited data are available concerning the time course of release and clearance of cf-DNA in vivo. METHODS We extracted cf-DNA from plasma samples taken before and immediately after a 10-km cross-country run, and from samples taken before, immediately after, and 30 min after exhaustive short-term treadmill exercise. The contribution of nuclear (nDNA) and mitochondrial DNA (mtDNA) was measured by quantitative real-time PCR. The incremental treadmill exercise setup was exploited to delineate the precise sequencing and timing of cf-nDNA, lactate, and high-mobility group box 1 protein (HMGB1) release during the exercise and recovery phases. RESULTS Postexercise plasma cf-nDNA concentrations in cross-country and treadmill runners were significantly increased, by 7.6-fold and 9.9-fold, respectively (P < 0.001). cf-nDNA concentrations were not correlated with age, sex, or body mass index. Plasma concentrations of cf-nDNA and HMGB1 in postexercise samples of treadmill runners were significantly correlated (r = 0.84; P = 0.004). cf-mtDNA concentrations were not affected by treadmill exercise. Time-course analyses demonstrated that cf-nDNA is released within minutes after the onset of exercise and is rapidly cleared from the circulation after the cessation of exercise. Nearly congruent kinetics for cf-nDNA, lactate, and HMGB1 were observed during the exercise phase. CONCLUSIONS A single bout of exhaustive short-term treadmill exercise constitutes a versatile model system suitable for addressing basic questions about cf-DNA biology.

scholarly journals TBIO-18. LIQUID BIOPSY DETECTION OF GENOMIC ALTERATIONS IN PEDIATRIC BRAIN TUMORS FROM CELL FREE DNA IN PERIPHERAL BLOOD, CSF, AND URINE

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i184-i184
Author(s):  
Melanie Pages ◽  
Denisse Rotem ◽  
Gregory Gydush ◽  
Sarah Reed ◽  
Justin Rhoades ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Pediatric Brain Tumors ◽  
Genomic Alterations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Pediatric Brain

Anti-viral properties of interferon beta treatment in patients with multiple sclerosis

2002 ◽  
Vol 8 (3) ◽  
pp. 237-242 ◽  
Author(s):  
J Hong ◽  
M V Tejada-Simon ◽  
V M Rivera ◽  
Y CQ Zang ◽  
J Z Zhang
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Efficacy ◽  
Interferon Beta ◽  
Viral Infections ◽  
Human Herpesvirus ◽  
Virion Protein ◽  
Cell Free Dna ◽  
Free Dna

Viral infections are potentially associated with the etiology and pathogenesis of multiple sclerosis (MS). It has been speculated that the treatment efficacy of interferon beta (IFN beta) in MS may relate to its anti-viral properties. The study was undertaken to evaluate the in vivo anti-viral effects of IFN beta-1a in patients with MS. Human herpesvirus-6 (HHV-6) was studied as an example for being a latent neurotropic virus. IFN beta used at concentrations of approximately 0.5 mg/ml was shown to significantly reduce in vitro HHV-6 replication in a susceptible T-cell line. Sera derived from 23 MS patients treated with IFN beta-1a were examined for serum cell-free DNA of HHV-6 as an indicator for viral replication and the reactivity of IgM antibodies to a recombinant HHV-6 virion protein containing a known immunoreactive region. The results were compared with those of control sera obtained from untreated MS (n=29) and healthy individuals (n=21). The findings indicated that IFN beta treatment significantly reduced HHV-6 replication as evident by decreased cell-free DNA in treated MS specimens. The results correlated with decreased IgM reactivity to the HHV-6 antigen in treated MS patients compared to untreated controls, suggesting reduced exposure to HHV-6. The findings were confirmed in paired sera obtained from seven MS patients before and after the treatment. The study provides new evidence indicating that IFN beta has potent in vivo anti-viral effects that may contribute to the treatment efficacy in MS.

Neutrophil Extracellular Traps May Contribute to the Pathogenesis in Adult-onset Still Disease

2019 ◽  
Vol 46 (12) ◽  
pp. 1560-1569 ◽  
Author(s):  
Mi-Hyun Ahn ◽  
Jae Ho Han ◽  
Young-Jun Chwae ◽  
Ju-Yang Jung ◽  
Chang-Hee Suh ◽  
...  
Keyword(s):  
Immunohistochemical Analysis ◽  
Serum Levels ◽  
Neutrophil Extracellular Traps ◽  
Polymorphonuclear Neutrophils ◽  
Adult Onset ◽  
Cell Free Dna ◽  
Extracellular Traps ◽  
Free Dna ◽  
Still Disease

Objective.Release of neutrophil extracellular traps (NET) has been described as an effector mechanism of polymorphonuclear neutrophils in several inflammatory diseases. Thus, this study was performed to evaluate the role of NET in the pathogenesis of adult-onset Still disease (AOSD).Methods.We determined the serum levels of NET molecules and investigated their associations with clinical disease activities in patients with AOSD. Further, we analyzed the differences in the NETosis response in AOSD patients compared to healthy controls (HC). To explore the in vivo involvement of NET in AOSD, we performed immunohistochemical analysis of skin and lymph node (LN) biopsies for proteins related to NET in patients with active AOSD.Results.Serum levels of cell-free DNA, myeloperoxidase (MPO)-DNA complex, and α-defensin were significantly increased in patients with AOSD compared to HC. Serum levels of the NET molecules, cell-free DNA, MPO-DNA, and α-defensin were correlated with several disease activity markers for AOSD. In followup of patients with AOSD after treatment with corticosteroid, the levels of cell-free DNA and α-defensin decreased significantly. On immunohistochemistry, neutrophil elastase–positive and MPO-positive inflammatory cells were detected in skin and LN of patients with AOSD, and were expressed in fiber form in the lesions. The serum from patients with active AOSD induced NETosis in neutrophils from HC. NET molecules induced interleukin 1β production in monocytes, representing a novel mechanism in the pathogenesis of AOSD.Conclusion.The findings presented here suggest that NET may contribute to the inflammatory response and pathogenesis in AOSD.

scholarly journals GENE-07. LIQUID BIOPSY DETECTION OF GENOMIC ALTERATIONS IN PEDIATRIC BRAIN TUMORS FROM CELL-FREE DNA IN PERIPHERAL BLOOD, CSF, AND URINE

2019 ◽  
Vol 21 (Supplement_2) ◽  
pp. ii82-ii82
Author(s):  
Mélanie Pagès ◽  
Denisse Rotem ◽  
Gregory Gydush ◽  
Sarah Reed ◽  
Justin Rhoades ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Pediatric Brain Tumors ◽  
Genomic Alterations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Pediatric Brain

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 INNV-22. LIQUID BIOPSY DETECTION OF GENOMIC ALTERATIONS IN PEDIATRIC BRAIN TUMORS FROM CELL FREE DNA IN PERIPHERAL BLOOD, CSF, AND URINE

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi142-vi143
Author(s):  
Mélanie Pages ◽  
Denisse Rotem ◽  
Gregory Gydush ◽  
Sarah Reed ◽  
Justin Rhoades ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Peripheral Blood ◽  
Liquid Biopsy ◽  
Pediatric Brain Tumors ◽  
Genomic Alterations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Pediatric Brain
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