Mi, Y;
Burnham, KL;
Charles, PD;
Heilig, R;
Vendrell, I;
Whalley, J;
Torrance, HD;
... Mills, G; + view all
(2024)
High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response.
Science Translational Medicine
, 16
(750)
, Article eadh0185. 10.1126/scitranslmed.adh0185.
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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.
| Type: | Article |
|---|---|
| Title: | High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/scitranslmed.adh0185 |
| Publisher version: | http://dx.doi.org/10.1126/scitranslmed.adh0185 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Humans, Sepsis, Proteome, Biomarkers, Proteomics, Male, Blood Proteins, Female, Middle Aged, Tandem Mass Spectrometry |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10194183 |
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