High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response
Authors: Yuxin Mi, Katie L. Burnham, Philip D. Charles, Raphael Heilig, Iolanda Vendrell, Justin Whalley, Hew D. Torrance, David B. Antcliffe, Shaun M. May, Matt J. Neville, Georgina Berridge, Paula Hutton, Cyndi G. Geoghegan, Jayachandran Radhakrishnan, Alexey I. Nesvizhskii, Fengchao Yu, Emma E. Davenport, Stuart McKechnie, Roger Davies, David J. P. O’Callaghan, Parind Patel, Ana G. del Arroyo, Fredrik Karpe, Anthony C. Gordon, Gareth L. Ackland, Charles J. Hinds, Roman Fischer, Julian C. Knight, Nigel Webster, Helen Galley, Jane Taylor, Sally Hall, Jenni Addison, Sian 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 Brett, David Kitson, Robert Wilson, Laura Mountford, Juan Moreno, Peter Hall, Jackie Hewlett, Christopher Garrard, Julian Millo, Duncan Young, Penny Parsons, Alex Smiths, Roser Faras-Arraya, Jasmeet Soar, Parizade Raymode, Jonathan Thompson, Sarah Bowrey, Sandra Kazembe, Natalie Rich, Prem Andreou, Dawn Hales, Emma Roberts, Simon Fletcher, Melissa Rosbergen, Georgina Glister, Jeronimo Moreno 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 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 Andrews, Sarah Mappleback, Chris Garrard, D. 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 Marshall, Hugh Montgomery, Jung Hyun Ryu, Georgia Bercades, Susan Boluda, Andrew Bentley, Katie Mccalman, Fiona Jefferies, Andrew Kwok, Narelle Maugeri, Jayachandran Radhakrishnan, Alice Allcock
Journal: Science Translational Medicine (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.