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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02953-4

摘要内容如下：

急性和慢性冠状动脉综合征（ACS和CCS）是死亡的主要原因。炎症被认为是这些疾病的关键致病驱动因素，但对其潜在的免疫状态及其临床意义仍知之甚少。多组因子分析（MOFA）允许跨多种数据类型的无监督数据探索，识别变异的主轴并将其与潜在的分子过程相关联。我们假设将MOFA应用于从血液中获得的多组学数据可能会揭示隐藏的差异来源，并提供与临床需求相关的病理生理学见解。在这里，我们编制了ACS和CCS（总共n=62名患者，n=15名女性和n=47名男性）的系统免疫状况的纵向多组学数据集，并在外部队列（总共n=55名患者，n=11名女性和n=44名男性）中对此进行了验证。MOFA揭示了以不同的单核细胞、自然杀伤细胞和T细胞亚群以及免疫通讯途径为特征的多细胞免疫信号，这解释了很大一部分患者间差异。我们还确定了反映疾病状态或与ACS治疗结果相关的特定因素，如使用左心室射血分数测量。因此，该研究为MOFA揭示心血管疾病中多细胞免疫程序的能力提供了概念验证证据，为机制、生物标志物和治疗研究开辟了新的方向。

英文原文如下：

Abstracts

Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver of these diseases, but the underlying immune states and their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple data types, identifying major axes of variation and associating these with underlying molecular processes. We hypothesized that applying MOFA to multiomic data obtained from blood might uncover hidden sources of variance and provide pathophysiological insights linked to clinical needs. Here we compile a longitudinal multiomic dataset of the systemic immune landscape in both ACS and CCS (n = 62 patients in total, n = 15 women and n = 47 men) and validate this in an external cohort (n = 55 patients in total, n = 11 women and n = 44 men). MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates and immune-communication pathways that explain a large proportion of inter-patient variance. We also identify specific factors that reflect disease state or associate with treatment outcome in ACS as measured using left ventricular ejection fraction. Hence, this study provides proof-of-concept evidence for the ability of MOFA to uncover multicellular immune programs in cardiovascular disease, opening new directions for mechanistic, biomarker and therapeutic studies.

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