An improved analytic workflow for serum mtDNA DAMP abundance, fragmentation and heteroplasmic variants: a retrospective analysis of acute respiratory failure patients

Scientific Reports 2026 Open access

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Authors: Grant T. Daly, Emily M. Hartsell, Viktor M. Pastukh, Justin T. Roberts, Adeyeye I. Haastrup, Lina D. Purcell, Madhuri S. Mulekar, D. Clark Files, Peter E. Morris, Mark N. Gillespie, Raymond J. Langley
DOI: 10.1038/s41598-026-51417-x
Cited by: 1
References: 60

Abstract

Serum mitochondrial DNA (mtDNA) fragments act as proinflammatory damage-associated molecular patterns (DAMPs), and have been linked to outcomes in critical illness. However, the prognostic value of mtDNA DAMPs remains uncertain, possibly due to confounding nuclear mitochondrial insertions (NUMTs), which obscure both quantitation and variant detection. We developed a deep sequencing and bioinformatics workflow to minimize NUMT-related artifacts. By modeling insert size distributions in ICU patients with acute respiratory failure, we excluded likely NUMT-derived fragments, improving the accuracy of mtDNA DAMP fragmentomic analysis. Short inserts (

Fields of Study & Subjects

Mitochondrial Function and Pathology Sepsis Diagnosis and Treatment GDF15 and Related Biomarkers

Publication details

Journal / source
Scientific Reports
Publisher
Springer Science and Business Media LLC
Volume
16
Issue
1
Publication date
23 May 2026
Language
EN