High-throughput mass spectrometry maps the sepsis plasma proteome and differences in response
High-throughput mass spectrometry maps the sepsis plasma proteome and differences in response
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DOI：
10.1101/2022.08.07.22278495
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发表时间：
2022-08
期刊：
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通讯作者：
Yuxin Mi;K. Burnham;P. Charles;R. Heilig;I. Vendrell;J. Whalley;H. Torrance;D. Antcliffe;S. May;M. Neville;Georgina;Berridge;P. Hutton;Cyndi Goh;J. Radhakrishnan;A. Nesvizhskii;Fengchao Yu;E. Davenport;S. McKechnie;R. Davies;D. O'Callaghan;P. Patel;F. Karpe;A. Gordon;G. Ackland;Charles Hinds;R. Fischer;J. Knight
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作者：
Yuxin Mi;K. Burnham;P. Charles;R. Heilig;I. Vendrell;J. Whalley;H. Torrance;D. Antcliffe;S. May;M. Neville;Georgina;Berridge;P. Hutton;Cyndi Goh;J. Radhakrishnan;A. Nesvizhskii;Fengchao Yu;E. Davenport;S. McKechnie;R. Davies;D. O'Callaghan;P. Patel;F. Karpe;A. Gordon;G. Ackland;Charles Hinds;R. Fischer;J. Knight
脓毒症是宿主对感染的失调反应，导致危及生命的器官功能障碍，是一个尚未解决的全球健康挑战。在这里，我们应用高通量串联质谱法来描绘脓毒症组和对照组（未感染的危重病、术后炎症和健康志愿者）的血浆蛋白质组，涉及单批 2622 个样本和 4553 个液相色谱-质谱分析，每天 100 个样本。我们展示了这种规模的数据如何在脓毒症中建立共享和特定的蛋白质、途径和共表达模块，并使用矩阵分解与配对白细胞转录组数据（n = 837 个样本）整合。我们绘制了脓毒症宿主反应的情况，包括随时间的变化，并确定了与病因、临床表型和严重程度相关的特征。这项工作揭示了脓毒症反应状态、疾病过程和结果的新亚表型，突出了药物靶点的潜在生物标志物、途径和过程，并推进了基于系统的脓毒症精准医学方法。
Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is an unmet global health challenge. Here we apply high-throughput tandem mass spectrometry to delineate the plasma proteome for sepsis and comparator groups (non-infected critical illness, post-operative inflammation and healthy volunteers) involving 2622 samples and 4553 liquid chromatography-mass spectrometry analyses in a single batch, at 100 samples/day. We show how this scale of data can establish shared and specific proteins, pathways and co-expression modules in sepsis, and be integrated with paired leukocyte transcriptomic data (n=837 samples) using matrix decomposition. We map the landscape of the host response in sepsis including changes over time, and identify features relating to etiology, clinical phenotypes and severity. This work reveals novel subphenotypes informative for sepsis response state, disease processes and outcome, highlights potential biomarkers, pathways and processes for drug targets, and advances a systems-based precision medicine approach to sepsis.