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- Title
High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response.
- Authors
Mi, Yuxin; Burnham, Katie L.; Charles, Philip D.; Heilig, Raphael; Vendrell, Iolanda; Whalley, Justin; Torrance, Hew D.; Antcliffe, David B.; May, Shaun M.; Neville, Matt J.; Berridge, Georgina; Hutton, Paula; Geoghegan, Cyndi G.; Radhakrishnan, Jayachandran; Nesvizhskii, Alexey I.; Yu, Fengchao; Davenport, Emma E.; McKechnie, Stuart; Davies, Roger; O'Callaghan, David J. P.
- Abstract
Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of pathophysiology and new therapeutic approaches. Here, we applied high-throughput tandem mass spectrometry to delineate the plasma proteome for sepsis and comparator groups (noninfected critical illness, postoperative inflammation, and healthy volunteers) involving 2612 samples (from 1611 patients) and 4553 liquid chromatography–mass spectrometry analyses acquired through a single batch of continuous measurements, with a throughput of 100 samples per day. We show how this scale of data can delineate proteins, pathways, and coexpression modules in sepsis and be integrated with paired leukocyte transcriptomic data (837 samples from n = 649 patients). We mapped the plasma proteomic landscape of the host response in sepsis, including changes over time, and identified features relating to etiology, clinical phenotypes (including organ failures), and severity. This work reveals subphenotypes informative for sepsis response state, disease processes, and outcome; identifies potential biomarkers; and advances opportunities for a precision medicine approach to sepsis. Editor's summary: Sepsis is caused by an extreme immune response to infection and can damage organs and potentially lead to death. To better understand what happens to the body during sepsis, Mi et al. comprehensively profiled the plasma proteomes of ICU patients with sepsis. The longitudinal nature of their sampling allowed the authors to assess changes in the plasma proteome over time and to assess heterogeneity in patient responses. The group also profiled relevant comparator groups, including noninfected ICU patients, individuals with postoperative inflammation, and healthy individuals, allowing for the detection of sepsis-specific responses. This study offers insights into sepsis biology and a valuable resource for further research. —Catherine Charneski
- Subjects
SEPSIS; MASS spectrometry; INDUCTIVELY coupled plasma mass spectrometry; LIQUID chromatography-mass spectrometry; TANDEM mass spectrometry
- Publication
Science Translational Medicine, 2024, Vol 16, Issue 750, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.adh0185