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High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response

2024; American Association for the Advancement of Science; Volume: 16; Issue: 750 Linguagem: Inglês

10.1126/scitranslmed.adh0185

1946-6242

Yuxin Mi, Katie L. Burnham, Philip D. Charles, Raphael Heilig, Iolanda Vendrell, Justin P. Whalley, Hew D.T. Torrance, David Antcliffe, Shaun M. May, Matt J. Neville, G. Berridge, Paula Hutton, Cyndi G. Geoghegan, Jayachandran Radhakrishnan, Alexey I. Nesvizhskii, Fengchao Yu, Emma E. Davenport, Stuart McKechnie, R. G. Davies, David JP O’Callaghan, P. Patel, Ana Gutierrez del Arroyo, Fredrik Karpe, Anthony Gordon, Gareth L. Ackland, Charles Hinds, Román Fischer, Julian C. Knight, Nigel R. Webster, Helen F. Galley, Jane R. Taylor, Sally Hall, Jenni Addison, Siân Roughton, Heather Tennant, Achyut Guleri, Natalia Waddington, Dilshan Arawwawala, John Durcan, Alasdair Short, Karen Swan, Sarah Williams, Susan Smolen, Christine Mitchell-Inwang, Emily Errington, Maie Templeton, Pyda Venatesh, Geraldine Ward, Marie McCauley, Simon Baudouin, Charley Higham, Jasmeet Soar, Sally Grier, Elaine Hall, Stephen J. Brett, David H. Kitson, Robert Wilson, Laura Mountford, Juan C. Moreno, Peter Hall, Jackie Hewlett, Christopher S. Garrard, Julian Millo, Duncan Young, Penny Parsons, Alex Smiths, Roser Faras-Arraya, Jasmeet Soar, Parizade Raymode, Jonathan P. Thompson, Sarah Bowrey, Sandra Kazembe, Natalie Rich, Prem Andreou, Dawn Hales, Emma A. Roberts, Simon P. Fletcher, Melissa Rosbergen, Georgina Glister, Jeronimo Cuesta, Julian Bion, Joanne Millar, Elsa Jane Perry, Heather Willis, Natalie Mitchell, Sebastian Ruel, Ronald Carrera, Jude Wilde, Annette Nilson, Sarah Lees, Atul Kapila, Nicola Jacques, Jane C. Atkinson, Abby Brown, Heather Prowse, Anton Krige, Martin Bland, Lynne Bullock, Donna Harrison, Gary Mills, John Humphreys, Kelsey Armitage, Shond Laha, Jacqueline Baldwin, Angela Walsh, Nicola Doherty, Stephen Drage, Laura Ortiz-Ruiz de Gordoa, Sarah Lowes, Charley Higham, Helen Walsh, Verity Calder, Catherine Swan, Heather Payne, David Higgins, Sarah F. Andrews, Sarah Mappleback, Chris Garrard, David Watson, Eleanor McLees, Alice Purdy, Martin Stotz, Adaeze Ochelli-Okpue, Stephen Bonner, Iain Whitehead, Keith Hugil, Victoria Goodridge, Louisa Cawthor, Martin Kuper, Sheik Pahary, Geoffrey Bellingan, Richard S. Marshall, Hugh Montgomery, Jung Hyun Ryu, Georgia Bercades, Susan Boluda, Andrew Bentley, Katie Mccalman, Fiona Jefferies, Andrew Kwok, Narelle Maugeri, Jayachandran Radhakrishnan, Alice Allcock,

Sepsis Diagnosis and Treatment

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.