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Cell-free DNA Methylomics Identify Tissue Injury Patterns in Pediatric ARDS

ABSTRACT: Cell-free DNA Methylomics Identify Tissue Injury Patterns in Pediatric ARDS

PROVIDER: PRJNA1211168 | ENA |

REPOSITORIES: ENA

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Cell-free DNA Methylomics Identify Tissue Injury Patterns in Pediatric ARDS

Project description:Cell-free DNA (cfDNA) is released into the circulation from dead and dying cells, and is elevated in critical illness syndromes including sepsis and acute respiratory distress syndrome (ARDS). Plasma cfDNA has been implicated as a damage-associated molecular pattern (DAMP) that propagates ongoing inflammation. However, the tissue source of circulating cfDNA from different pathological processes has not been fully elucidated, and identification of the cellular origin of cfDNA may provide insight into the mechanisms underlying the early inflammatory response. As cfDNA retains the unique methylation pattern of its tissue of origin, we can leverage cfDNA methylome to map the presumed tissue of origin of these DAMPs. We conducted a pilot study to assess the cfDNA methylation pattern in pediatric ARDS.

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Project description:The objective of this study was to identify differences in the nasal methylome of patients with Pediatric ARDS (PARDS) compared to controls and to observe how this might change over time. We found two different methylomic patterns. Subgroup 1 was comprised of entirely of PARDS subjects, and Subgroup 2 contained both control and PARDS subject. Subgroup 1was characterized by hypomethylation of genes related to cell adhesion and hypermethylation of cell metabolism-related genes. Over time, the methylation pattern of PARDS subjects changed, but the pattern of control subjects was stable. Five concurrent bronchial and nasal specimens were obtained showing very few differences in methylation between these two collection sites.

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