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 ,   GAinS Investigators, Davenport Emma E. , McKechnie Stuart , Davies Roger , O’Callaghan David J. P. , Patel Parind , del Arroyo Ana G. , Karpe Fredrik , Gordon Anthony C. , Ackland Gareth L. , Hinds Charles J. , Fischer Roman , Knight Julian C. , Webster Nigel , Galley Helen , Taylor Jane , Hall Sally , Addison Jenni , Roughton Sian , Tennant Heather , Guleri Achyut , Waddington Natalia , Arawwawala Dilshan , Durcan John , Short Alasdair , Swan Karen , Williams Sarah , Smolen Susan , Mitchell-Inwang Christine , Errington Emily , Templeton Maie , Venatesh Pyda , Ward Geraldine , McCauley Marie , Baudouin Simon , Higham Charley , Soar Jasmeet , Grier Sally , Hall Elaine , Brett Stephen , Kitson David , Wilson Robert , Mountford Laura , Moreno Juan , Hall Peter , Hewlett Jackie , Garrard Christopher , Millo Julian , Young Duncan , Parsons Penny , Smiths Alex , Faras-Arraya Roser , Soar Jasmeet , Raymode Parizade , Thompson Jonathan , Bowrey Sarah , Kazembe Sandra , Rich Natalie , Andreou Prem , Hales Dawn , Roberts Emma , Fletcher Simon , Rosbergen Melissa , Glister Georgina , Cuesta Jeronimo Moreno , Bion Julian , Millar Joanne , Perry Elsa Jane , Willis Heather , Mitchell Natalie , Ruel Sebastian , Carrera Ronald , Wilde Jude , Nilson Annette , Lees Sarah , Kapila Atul , Jacques Nicola , Atkinson Jane , Brown Abby , Prowse Heather , Krige Anton , Bland Martin , Bullock Lynne , Harrison Donna , Mills Gary , Humphreys John , Armitage Kelsey , Laha Shond , Baldwin Jacqueline , Walsh Angela , Doherty Nicola , Drage Stephen , de Gordoa Laura Ortiz-Ruiz , Lowes Sarah , Higham Charley , Walsh Helen , Calder Verity , Swan Catherine , Payne Heather , Higgins David , Andrews Sarah , Mappleback Sarah , Garrard Chris , Watson D. , McLees Eleanor , Purdy Alice , Stotz Martin , Ochelli-Okpue Adaeze , Bonner Stephen , Whitehead Iain , Hugil Keith , Goodridge Victoria , Cawthor Louisa , Kuper Martin , Pahary Sheik , Bellingan Geoffrey , Marshall Richard , Montgomery Hugh , Ryu Jung Hyun , Bercades Georgia , Boluda Susan , Bentley Andrew , Mccalman Katie , Jefferies Fiona , Kwok Andrew , Maugeri Narelle , Radhakrishnan Jayachandran , Allcock Alice 
Published: June 2024

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.