Enhancing liquid biopsies
Liquid biopsies, analyses of cell-free DNA that circulates in the blood, can be used in prenatal testing, oncology, and to monitor organ transplant recipients. Lo et al. review the nongenetic information that can be gleaned from analyses of cell-free DNA, which offers additional promise for the applications of this procedure. These analyses include DNA methylation patterns, fragmentation profiles, and topology, which can be informative about the health and origin of the tissue from which they are derived.
Science, this issue p. eaaw3616
Liquid biopsies that are based on analysis of cell-free DNA from plasma offer diagnostic information that is otherwise accessible conventionally through invasive biopsies. Noninvasive prenatal testing has been used globally for the screening of fetal chromosomal aneuploidies and has led to a considerable reduction in invasive prenatal testing, such as use of amniocentesis. Cancer liquid biopsies have been used for the selection of targeted therapies and monitoring of disease progression. Liquid biopsies for organ transplant patients have been used to monitor graft dysfunction. The first applications of liquid biopsies are based on the detection of genetic markers in cell-free DNA, such as sex differences, genetic polymorphisms, or mutations. By studying nongenetic features of cell-free DNA moleculesincluding DNA methylation, fragmentation, and topologyunderstanding of cell-free DNA biology has expanded the spectrum and utilities of liquid biopsies.
Cell-free DNA in plasma consists of a mixture of fragmented DNA molecules released from various tissues within the body. Each cell-free DNA fragment bears molecular signatures of its cell of origin, such as DNA methylation status. The methylation profile of circulating fetal DNA in the mothers plasma correlates with that of the placenta and has been exploited as a means to develop noninvasive fetus-specific biomarkers that are not dependent on fetal sex or genotype. Circulating tumor-derived DNA bear methylation states that resemble the tumor tissue and have enabled the development of tests for the screening and localization of cancer. The fragmentation of plasma DNA is related to the nucleosomal organization, chromatin structure, gene expression, and nuclease content of the tissue of origin, resulting in characteristic signatures in the form of fragment size, nucleotide motifs at the fragment ends, single-stranded jagged ends, and the genomic locations of the fragmentation endpoints. For mitochondrial DNA that is originally in a circular form, fragmentation will also change its topology into a linear form. By noting these features of cell-free DNA fragments, the anatomical site of pathology could potentially be deduced, providing additional information than just quantifying mitochondrial DNA without regard to its form. The study of such characteristics has also enhanced our understanding of the biology and generation of cell-free DNA. The roles of nucleases in plasma DNA biology, such as deoxyribonuclease 1like-3, have been explored by using gene-deletion mouse models and confirmed in humans bearing nuclease gene mutations, with potential implications for the pathogenesis of autoimmune diseases.
The use of DNA methylation, fragmentomic, and topologic analyses of circulating DNA, either in a targeted fashion or in a genomewide manner, will be expected to impact clinical practice. Clinical specimens covering more disease entities will need to be investigated to identify tissue-specific and disease-relevant signatures. During the discovery phase, to better delineate these signatures, mining is performed on high volumes of DNA data pooled within and across samples by using customized bioinformatics algorithms. Once these putative sets of signatures have been identified, signature- and target-specific assays could be developed, and large-scale clinical trials will be needed to validate these approaches. One application is in the development of plasma DNAbased cancer screening. One advantage of these approaches is the potentially large number of markers that can be developed to differentiate cancer and noncancer cells and in the ability to locate the tissue of origin of the detected cancer, possibly including cancers of unknown primary. In the area of noninvasive prenatal testing, the correlation of DNA methylation, fragmentomic, and topologic aberrations in circulating DNA to clinical outcomes would expand the spectrum of diagnostic applications beyond current ones. Fragmentomic approaches have the potential for enriching the cell-free DNA species of interest, such as through the use of automated platforms that allow the size separation of circulating DNA. In the area of organ transplant monitoring, the development of DNA methylation, fragmentomic, and topologic markers would provide an alternative to genetic markers for detecting rejection. These nongenetic markers may enable further differentiation of the donors contribution to the circulating DNA pool into its constituent tissue components. The understanding between circulating DNA and nucleases is in its infancy. Circulating DNA signatures attributable to changes in nuclease expression in health and disease need to be elucidated and may have emerging diagnostic applications.
Different tissues, including cancer cells and trophoblasts in pregnancy, contribute cell-free DNA to the circulation. The cell-free DNA molecules may bear methylation states reflective of the cell of origin. The DNA molecule size, fragment end locations, and end motifs are influenced by the nucleosome organization, chromatin structure, nuclease content, and gene expression of the tissue of origin. Parameters that can be measured to quantify these characteristics are shown on the right.
Liquid biopsies that analyze cell-free DNA in blood plasma are used for noninvasive prenatal testing, oncology, and monitoring of organ transplant recipients. DNA molecules are released into the plasma from various bodily tissues. Physical and molecular features of cell-free DNA fragments and their distribution over the genome bear information about their tissues of origin. Moreover, patterns of DNA methylation of these molecules reflect those of their tissue sources. The nucleosomal organization and nuclease content of the tissue of origin affect the fragmentation profile of plasma DNA molecules, such as fragment size and end motifs. Besides double-stranded linear fragments, other topological forms of cell-free DNA also existnamely circular and single-stranded molecules. Enhanced by these features, liquid biopsies hold promise for the noninvasive detection of tissue-specific pathologies with a range of clinical applications.
Continue reading here:
Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies - Science
- The Role of Epigenetics and Contributing Impact of Stress, Multigenerational, and Developmental Factors in Opiate ... - Cureus - February 8th, 2024
- About Epigenetics | Johns Hopkins Institute of Genetic Medicine - November 16th, 2023
- What is Epigenetics? - Bruce H. Lipton, PhD - January 4th, 2023
- Why Epigenetics Contradicts Evolutionary Theory | Evolution News - December 18th, 2022
- Epigenetics in Psychology | Noba - November 24th, 2022
- Epigenetics: Definition, Mechanisms and Clinical Perspective - November 24th, 2022
- Researchers Find that Moms Pass On Additional Epigenetic Information To Their Children - WhatIsEpigenetics.com - October 13th, 2022
- Prestigious award advances OHSU research on impact of drug use over generations - OHSU News - October 13th, 2022
- Hoylake doctor launches test that detects diseases before they appear - Wirral Globe - October 13th, 2022
- Xenetic Biosciences, Inc. Announces Signing of Patent Assignment Related to Collaboration With VolitionRx Limited and CLS Therapeutics - Yahoo Finance - October 13th, 2022
- Understanding the Epigenetics of Childhood Trauma - Psych Central - October 4th, 2022
- Epigenetic therapy promotes spinal cord regeneration in mice following injury - RegMedNet - October 4th, 2022
- ORYZON to Give Updates on Corporate Progress in October - Yahoo Finance - October 4th, 2022
- InvestmentPitch Media Video Discusses Resverlogix and its Focus on Apabetalone's Future Development for the Prevention and Treatment of Post COVID-19... - October 4th, 2022
- Cardio Diagnostics To Sponsor, Participate in the American Heart Association's 2022 Metro Chicago Heart Walk - Yahoo Finance - September 16th, 2022
- Book review: Daughters and the stories they carry - Yahoo News - September 16th, 2022
- Inherent Biosciences raises funding to expand fertility care though epigenetics - VatorNews - September 8th, 2022
- 10 wellness retreat trends to know about - Cond Nast Traveller - September 8th, 2022
- Spotlight: Women in Science: Dr. Judith Kassis on Pursuing the Unexpected - National Institute of Child Health and Human Development - September 8th, 2022
- Epigenetic Information Passed On to Offspring More Frequently Than Once Thought - Technology Networks - August 22nd, 2022
- New discovery shows you may inherit more from your mom than you think - EastMojo - August 22nd, 2022
- New Technology to Understand Cell Types and How Diseases Develop - Yale University - August 22nd, 2022
- Research Roundup: Fat Cell Hormone Slows Liver Tumor Growth and More Research News - BioSpace - August 22nd, 2022
- De-extinction? Plans to revive Tasmanian tiger triggers... - The American Bazaar - August 22nd, 2022
- Epigenetics in Health and Disease - PubMed - August 14th, 2022
- Clinical Epigenetics | Home page - August 14th, 2022
- Efficacy of Neoadjuvant Immunotherapy on Breast Cancer is Independent of Race - Pharmacy Times - August 14th, 2022
- Your True Age Might Not Be Your Birthdate And Thats Good News - Goalcast - August 14th, 2022
- Epigenetics Market is Predicted to Hit $6460.5 Million Value by 2030, says P&S Intelligence - PR Newswire UK - July 27th, 2022
- ORYZON Collaborates with the CMT Research Foundation in the US - Yahoo Finance - July 27th, 2022
- What is schizophrenia? Common myths and misconceptions around the mental illness - The Mirror - July 27th, 2022
- What gene changes and blood could tell us about the opioid crisis - UCI News - July 19th, 2022
- Epigenetics Is The Key To Treating Complex Diseases; Dr. Nirmalya Saha Is Using It To Unlock Cancer Treatment And More - EconoTimes - July 19th, 2022
- Heatstroke stresses the body years after the original heat illness - University of Florida - July 19th, 2022
- Omega Therapeutics Announces FDA Clearance of IND Application for OTX-2002, First Omega Epigenomic Controller, for MYC Driven Hepatocellular Carcinoma... - July 19th, 2022
- Genetics proposes, epigenetics disposes: how our approach to human health changes in the 21st century and how CRISPR-Cas is involved - Digital Journal - June 22nd, 2022
- Zenith Epigenetics Triple Negative Breast Cancer Clinical Data Highlighted in an Oral Discussion at the American Society of Clinical Oncology... - June 22nd, 2022
- The relationship between P16INK4A and TP53 promoter methylation and the risk and prognosis in patients with oesophageal cancer in Thailand |... - June 22nd, 2022
- Omega Therapeutics (OMGA) Research Analysts' Weekly Ratings Changes - Defense World - June 13th, 2022
- Introducing Cantata Bio, Inventive Multimodal Solutions for Accelerating Genome-based R&D - Business Wire - June 13th, 2022
- Plant biologist nominated for prestigious early career award - University of Georgia - June 13th, 2022
- Julee Cruise's Career: How and where to watch Twin Peaks and all her TV appearances - Bolavip US - June 13th, 2022
- Hitting the Pro Race Track: Onovi Health Adds Marko Radiic, Professional Race Car Driver & Entrepreneur, as a Brand Ambassador - PR Newswire - June 13th, 2022
- Epigenetics: Definition & Examples | Live Science - June 4th, 2022
- Genetics and Epigenetics of Addiction DrugFacts | National Institute on ... - June 4th, 2022
- Epigenetics Market is Growing Rapidly with Recent Demand, Trends, Development, Revenue and Forecast to 2029 The Greater Binghamton Business Journal -... - June 4th, 2022
- Epigenetics at the Intersection of COVID-19 Risk and Environmental Chemical Exposures - DocWire News - June 4th, 2022
- Global Epigenetics Instrument Market 2022 Covid 19 Impact on Top countries data |Illumina, Thermo Fisher, Diagenode The Greater Binghamton Business... - June 4th, 2022
- Global Biomarkers Market Outlook & Forecast 2022-2027: Increase In Number of Pipeline Biomarkers & Rising Adoption of Biomarkers In Disease... - June 4th, 2022
- Many African Americans face unresolved trauma of racism and enslavement; It's affecting their health - ideastream - June 4th, 2022
- Zenith Epigenetics Announces Initiation of a Phase 2b Triple Negative Breast Cancer (TNBC) Clinical Trial - BioSpace - May 15th, 2022
- Gene edited rats cured of anxiety and alcoholism | SYFY WIRE - Syfy - May 15th, 2022
- Dreams on Fire sheds light on epigenetics, collective trauma of genocide traveling through generations - Armenian Weekly - May 2nd, 2022
- NEAR science: good for what ails stressed communities - NUjournal - May 2nd, 2022
- Digital biomarkers - An Emerging tool in precision Medicines. The Biomarkers Market to Reach $86 Billion by 2027 - Arizton - Yahoo Finance - May 2nd, 2022
- Sprint Bioscience's NIMA program is focused on the target protein NNMT and will be launched at the BIO International convention - Marketscreener.com - May 2nd, 2022
- Post-Doctoral Associate in the Center for Genomics and Systems Biology job with NEW YORK UNIVERSITY ABU DHABI | 291713 - Times Higher Education - May 2nd, 2022
- Womb with a View: On the Science of Maternal Effects - lareviewofbooks - April 19th, 2022
- Molecular Biology Enzymes, Kits & Reagents Market likely to bring in approximately US$ 22000 Million revenues by 2026-end Political Beef -... - April 19th, 2022
- Type 2 diabetes on the rise among Wisconsin children - Iron Mountain Daily News - April 19th, 2022
- January 2022: Exposures, diverse populations, and epigenetics merge in grantee's lab - Environmental Factor Newsletter - January 5th, 2022
- Research Roundup: Why mRNA Vaccines are So Good Against Severe COVID-19 and More - BioSpace - January 5th, 2022
- Epigenetics - Genome.gov - December 24th, 2021
- Genetics, Epigenetics, and Cancer: What Data Are We Missing? - AJMC.com Managed Markets Network - December 24th, 2021
- Can epigenetics help solve the puzzle between concomitant cardiovascular injury and severity of COVID-19? - DocWire News - December 24th, 2021
- Genomics Market Revenue to Cross US$ 49996.15 by 2027: The Insight Partners - Digital Journal - December 24th, 2021
- Hydra regrow their heads and live forever due to epigenetics - Cosmos Magazine - December 10th, 2021
- Epigenetics Market to Garner US$ 2611.57 MN, Globally, by 2025 at 13.6% CAGR: The Insight Partners - Digital Journal - December 10th, 2021
- Research Associate or Research Assistant in Medical and Molecular Genetics job with KINGS COLLEGE LONDON | 274309 - Times Higher Education (THE) - December 10th, 2021
- Newpath Commits $350 Million to Fund the Next Good Things in the Life Sciences - BioSpace - December 10th, 2021
- Wind Turbine Market Development Overview And Analysis Till 2030- Market.Biz - Digital Journal - December 10th, 2021
- Cancer Testing Product Market to Witness Growth Acceleration | Epigenetics Ag, Techlab, Positive Bioscience Energy Siren - Energy Siren - November 22nd, 2021
- How can students make the best of their anxiety? - The Medium - November 22nd, 2021
- Epigenetic Study Links Smoke Exposure in Early Life to Advanced Aging - WhatIsEpigenetics.com - October 28th, 2021
- Salarius Pharmaceuticals (SLRX) is Developing a Novel LSD1 Inhibitor, Positioning it as a Significant Mover in Epigenetics-Based Cancer Therapies -... - October 28th, 2021
- Epigenetics-Based Kits Market To Witness High Growth In Near Future IMIESA - IMIESA - October 28th, 2021
- Epigenetics Diagnostic Market to Witness Growth Acceleration | Qiagen, Abcam plc, Novartis AG, Thermo Fisher Scientific IMIESA - IMIESA - October 28th, 2021
- LXRepair, Gustave Roussy Ink Research Partnership in Personalized Radiotherapy - Precision Oncology News - October 28th, 2021
- Van Andel Institute, Maine Medical Center Research Institute scientists earn $9.6 million Transformative Research Award from National Institutes of... - October 5th, 2021
- Epigenetics could reveal if you had a 'vanishing twin' - Popular Science - October 5th, 2021