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

Autor: Mi Y; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK., Burnham KL; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK., Charles PD; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK., Heilig R; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK., Vendrell I; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford OX3 7BN, UK., Whalley J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK., Torrance HD; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK., Antcliffe DB; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK.; Department of Critical Care, Imperial College Healthcare NHS Trust, London W2 1NY, UK., May SM; Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK., Neville MJ; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK.; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK., Berridge G; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK., Hutton P; Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7JX, UK., Geoghegan CG; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK., Radhakrishnan J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK., Nesvizhskii AI; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Yu F; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA., Davenport EE; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK., McKechnie S; Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7JX, UK., Davies R; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK., O'Callaghan DJP; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK.; Department of Critical Care, Imperial College Healthcare NHS Trust, London W2 1NY, UK., Patel P; Department of Critical Care, Imperial College Healthcare NHS Trust, London W2 1NY, UK., Del Arroyo AG; Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK., Karpe F; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK.; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK., Gordon AC; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK.; Department of Critical Care, Imperial College Healthcare NHS Trust, London W2 1NY, UK., Ackland GL; Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK., Hinds CJ; Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK., Fischer R; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford OX3 7BN, UK., Knight JC; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford OX3 7BN, UK.; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2024 Jun 05; Vol. 16 (750), pp. eadh0185. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1126/scitranslmed.adh0185
Abstrakt: 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.
Databáze: MEDLINE