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High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response.
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; 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.
Afiliación
  • 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.
  • Charles PD; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, 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.
  • Whalley J; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
  • Torrance HD; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford OX3 7BN, UK.
  • Antcliffe DB; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • May SM; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK.
  • Neville MJ; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK.
  • Berridge G; Department of Critical Care, Imperial College Healthcare NHS Trust, London W2 1NY, UK.
  • Hutton P; Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
  • Geoghegan CG; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK.
  • Radhakrishnan J; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.
  • Nesvizhskii AI; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
  • Yu F; Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7JX, UK.
  • Davenport EE; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • McKechnie S; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Davies R; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Patel P; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
  • Del Arroyo AG; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge CB10 1SA, UK.
  • Karpe F; Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7JX, UK.
  • Gordon AC; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK.
  • Ackland GL; Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK.
  • Hinds CJ; Department of Critical Care, Imperial College Healthcare NHS Trust, London W2 1NY, UK.
  • Fischer R; Department of Critical Care, Imperial College Healthcare NHS Trust, London W2 1NY, UK.
  • Knight JC; Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Sci Transl Med ; 16(750): eadh0185, 2024 Jun 05.
Article en En | MEDLINE | ID: mdl-38838133
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Proteoma Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Proteoma Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos