A consensus blood transcriptomic framework for sepsis.

To establish a standardized blood transcriptomic subtype model, we aggregated blood transcriptomics data from two major sepsis cohorts: the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) project (n = 678 sampled on intensive care unit admission; ClinicalTrials.gov registration no.

为了建立一个标准化的血液转录组亚型模型，我们汇总了两个主要的败血症队列的血液转录组数据：分子诊断和败血症风险分层（MARS）项目（n = 678，样本采集于重症监护病房入院时；ClinicalTrials.gov 注册号。

NCT01905033 ) and the Genomic Advances in Sepsis (GAinS) study (n = 444 sampled on intensive care unit admission and n = 817 follow-up samples; ClinicalTrials.gov registration no.

NCT01905033) 和基因组学在败血症中的进展（GAinS）研究（n = 444在重症监护病房入院时采样，n = 817随访样本；ClinicalTrials.gov 注册号。

NCT00131196 ).

NCT00131196）。

We demonstrate a strong interconnection across three separate classification methods, resulting in the proposed groupings of three consensus transcriptomic subtypes (CTSs).

我们展示了三种独立分类方法之间强烈的相互联系，从而提出了三种共识转录组亚型（CTSs）的建议分组。

The distinguishing characteristics of CTS1 included gene activation of typical inflammatory pathways, more pronounced endothelial activation and an overall immature neutrophil theme.

CTS1的区分特征包括典型炎症通路的基因激活、更为显著的内皮细胞激活以及整体未成熟中性粒细胞的主题。

CTS2 was characterized by gene activation of a heme metabolism pathway, fibrinolytic disturbances and platelet and eosinophil signatures.

CTS2 的特征是血红素代谢通路、纤溶紊乱以及血小板和嗜酸性粒细胞标志物的基因激活。

CTS3 was associated with genes involved in the activation of allograft rejection, interferon signaling and anticoagulation functions, together with lymphocyte and nonclassical monocyte features.

CTS3 与参与异体移植排斥反应、干扰素信号传导和抗凝功能的基因有关，同时还具有淋巴细胞和非经典单核细胞特征。

Evaluating CTS classification in independent patient cohorts, specifically the vasopressin vs noradrenaline as initial therapy in septic shock (VANISH) randomized controlled trial(n = 176; ISRCTN registration no.

在独立患者队列中评估CTs分类，特别是初始治疗为血管加压素与去甲肾上腺素在脓毒性休克中的比较（VANISH）随机对照试验（n = 176；ISRCTN注册号 ISRCTN20769191）以及在乌干达一个地区医院住院的疑似脓毒症患者（n = 128），确定了我们方法的稳健性。

ISRCTN20769191 ) and patients hospitalized with suspected sepsis at a district hospital in Uganda (n = 128), ascertained the robustness of our approach.

ISRCTN20769191）以及在乌干达一家地区医院因疑似败血症住院的患者（n = 128），验证了我们方法的稳健性。

Notably, post hoc analysis of a pseudo-randomized cohort, along with a reanalysis of the VANISH trial data, unmasked a harmful signal in CTS2-assigned patients treated with corticosteroids.

值得注意的是，对伪随机队列的事后分析以及对VANISH试验数据的重新分析揭示了接受皮质类固醇治疗的CTS2分配患者存在有害信号。

The CTS classification method aligns diverse sepsis transcriptomic subgroupings into a robust, reproducible framework, thereby enabling biological interpretation and potentially assisting aspects of clinical trial design to advance precision medicine in sepsis.

CTS分类方法将不同的脓毒症转录组亚组整合到一个稳健、可重复的框架中，从而使得生物学解释成为可能，并可能在临床试验设计中协助某些方面，以推进脓毒症的精准医学。