Abstract
The circulating cell-free nucleic acids (ccfNAs) are a mixture of single- or double-stranded nucleic acids, released into the blood plasma/serum by different tissues via apoptosis, necrosis, and secretions. Under healthy conditions, ccfNAs originate from the hematopoietic system, whereas under various clinical scenarios, the concomitant tissues release ccfNAs into the bloodstream. These ccfNAs include DNA, RNA, microRNA (miRNA), long non-coding RNA (lncRNA), fetal DNA/RNA, and mitochondrial DNA/RNA, and act as potential biomarkers in various clinical conditions. These are associated with different epigenetic modifications, which show disease-related variations and so finding their role as epigenetic biomarkers in clinical settings. This field has recently emerged as the latest advance in precision medicine because of its clinical relevance in diagnostic, prognostic, and predictive values. DNA methylation detected in ccfDNA has been widely used in personalized clinical diagnosis; furthermore, there is also the emerging role of ccfRNAs like miRNA and lncRNA as epigenetic biomarkers. This review focuses on the novel approaches for exploring ccfNAs as epigenetic biomarkers in personalized clinical diagnosis and prognosis, their potential as therapeutic targets and disease progression monitors, and reveals the tremendous potential that epigenetic biomarkers present to improve precision medicine. We explore the latest techniques for both quantitative and qualitative detection of epigenetic modifications in ccfNAs. The data on epigenetic modifications on ccfNAs are complex and often milieu-specific posing challenges for its understanding. Artificial intelligence and deep networks are the novel approaches for decoding complex data and providing insight into the decision-making in precision medicine.
Highlights
The diagnostic platform utilizing the detection of biomarkers in various body fluids called “liquid biopsy” can revolutionize precision medicine
CcfNAs present in blood circulation include cell-free genomic DNAs and cell-free mitochondrial DNA (mtDNA) (Kohler et al, 2009; Thierry et al, 2016) and cell-free RNAs including protein-coding messenger RNA, regulatory non-coding RNAs like microRNAs, long non-coding RNAs, circular RNAs, and RNAs involved in translation like transfer RNAs and ribosomal RNAs (Pos et al, 2018)
The various diagnostic approaches to study the epigenetic modifications in the nucleic acids include methylated CpG island recovery assay (MIRA) and MethylCap that rely on methyl-CpG-binding domains (MBD) to capture methylated DNA after DNA fractionation either by restriction digestion or sonication (Mitchell et al, 2011)
Summary
The diagnostic platform utilizing the detection of biomarkers in various body fluids called “liquid biopsy” can revolutionize precision medicine. As genetic biomarkers are less consistent and provide more variability across studies, epigenetic markers, which are more generalized between samples, present as a promising alternative for early diagnosis and monitoring of the diseases These epigenetic marks are tissue specific and reflect the pattern of disease progression (Zeng et al, 2019). The use of epigenetic marks has revolutionized the field of non-invasive molecular diagnosis replacing traditional screening and treatment methods These assays have great potential in future precise patient care. The development of advanced analytical software techniques like machine learning and artificial intelligence can enhance precision medicine (Ahlquist, 2018; BeltranGarcia et al, 2019) These are used in combination with next-generation sequencing to identify novel ccfNA-based epigenetic markers
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