Typical sizes of cfDNA fragments reflect chromatosome particles (~165bp), as well as multiples of nucleosomes, which protect DNA from digestion by apoptotic nucleases.
This includes but is not limited to trauma, sepsis, aseptic inflammation, myocardial infarction, stroke, transplantation, diabetes, and sickle cell disease.
[9] Recent studies have laid the foundation for inferring gene expression from cell-free DNA, with EPIC-seq emerging as a notable advancement.
[10] This method has substantially raised the bar for the noninvasive inference of expression levels of individual genes, thereby augmenting the assay's applicability in disease characterization, histological classification, and monitoring treatment efficacy.
[21][22] The ability to extract circulating tumor DNA (ctDNA) from the human plasma has led to huge advancements in noninvasive cancer detection.
[24] This type of biopsy is noninvasive and allows for the routine clinical screening that is important in determining cancer relapse after initial treatment.
[26] Oxidized mtDNA generated during programmed cell death is not limited to activate TLR9, but was shown to also engage the NLRP3 inflammasome, leading to the production of pro-inflammatory cytokines, IL-1β, and IL-18.
[30][32] MtDNA can also be recognized by cyclic GMP-AMP synthase (cGAS), a cytosolic dsDNA sensor to initiate a STING-IRF3-dependent pathway that in turn orchestrates the production of type I IFNs.
[35][36] At the moment, typical purification methods involve collection of blood via venipuncture, centrifugation to pellet the cells, and extraction of cfDNA from the plasma.
This deep sequencing is required to detect mutant circulating tumor DNA (ctDNA) present in low concentrations in the plasma.
[47][48] Due to the severity of sepsis in ICU patients, further testing in order to determine the scope of cfDNA efficacy as a biomarker for septic risk is likely.
[51] If the host body rejects the grafted organ the ddcfDNA concentration in the blood (plasma) will rise to a level greater than 5-fold higher than those without complications.
A combination of these biological features and technical feasibility of sampling, position cfDNA as a potential biomarker of enormous utility for example for autoimmune rheumatic diseases and tumors.
It offers also a potential biomarker with its own advantages over invasive tissue biopsy as a quantitative measure for detection of transplant rejection as well as immunosuppression optimisation.
Circulating nucleosomes, the primary repeating unit of DNA organization in chromatin, are quantified by enzyme-linked immunosorbent assays (ELISA).