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整合临床和代谢组学分析登革热感染,显示与疾病不同阶段宿主-病原体相互作用相关的分子特征。

Integrated clinical and metabolomic analysis of dengue infection shows molecular signatures associated with host-pathogen interaction in different phases of the disease.

机构信息

Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India.

STAR Laboratory, Central Research Instruments Facility, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Puttaparthi, Andhra Pradesh, 515134, India.

出版信息

Metabolomics. 2023 May 2;19(5):47. doi: 10.1007/s11306-023-02011-z.

DOI:10.1007/s11306-023-02011-z
PMID:37130982
Abstract

PURPOSE

Dengue is a mosquito vector-borne disease caused by the dengue virus, which affects 125 million people globally. The disease causes considerable morbidity. The disease, based on symptoms, is classified into three characteristic phases, which can further lead to complications in the second phase. Molecular signatures that are associated with the three phases have not been well characterized. We performed an integrated clinical and metabolomic analysis of our patient cohort and compared it with omics data from the literature to identify signatures unique to the different phases.

METHODS

The dengue patients are recruited by clinicians after standard-of-care diagnostic tests and evaluation of symptoms. Blood from the patients was collected. NS1 antigen, IgM, IgG antibodies, and cytokines in serum were analyzed using ELISA. Targeted metabolomics was performed using LC-MS triple quad. The results were compared with analyzed transcriptomic data from the GEO database and metabolomic data sets from the literature.

RESULTS

The dengue patients displayed characteristic features of the disease, including elevated NS1 levels. TNF-α was found to be elevated in all three phases compared to healthy controls. The metabolic pathways were found to be deregulated compared to healthy controls only in phases I and II of dengue patients. The pathways represent viral replication and host response mediated pathways. The major pathways include nucleotide metabolism of various amino acids and fatty acids, biotin, etc. CONCLUSION: The results show elevated TNF-α and metabolites that are characteristic of viral infection and host response. IL10 and IFN-γ were not significant, consistent with the absence of any complications.

摘要

目的

登革热是一种由登革病毒引起的蚊媒传染病,影响全球 1.25 亿人。这种疾病会导致相当高的发病率。根据症状,该疾病分为三个特征阶段,在第二阶段可能进一步导致并发症。与这三个阶段相关的分子特征尚未得到很好的描述。我们对我们的患者队列进行了综合的临床和代谢组学分析,并将其与文献中的组学数据进行了比较,以确定不同阶段特有的特征。

方法

临床医生在进行标准护理诊断测试和评估症状后招募登革热患者。从患者采集血液。使用 ELISA 分析血清中的 NS1 抗原、IgM、IgG 抗体和细胞因子。使用 LC-MS 三重四极杆进行靶向代谢组学分析。将结果与 GEO 数据库中的分析转录组数据和文献中的代谢组数据集进行比较。

结果

登革热患者表现出疾病的特征性特征,包括升高的 NS1 水平。与健康对照组相比,所有三个阶段的 TNF-α 均升高。与健康对照组相比,仅在登革热患者的 I 期和 II 期发现代谢途径失调。这些途径代表病毒复制和宿主反应介导的途径。主要途径包括各种氨基酸和脂肪酸、生物素等核苷酸代谢。

结论

结果表明,登革热患者存在升高的 TNF-α 和代谢物,这些特征与病毒感染和宿主反应有关。IL10 和 IFN-γ 并不显著,与没有任何并发症一致。

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Integrated multi-omic data analysis and validation with yeast model show oxidative phosphorylation modulates protein aggregation in amyotrophic lateral sclerosis.利用酵母模型进行的综合多组学数据分析与验证表明,氧化磷酸化调节肌萎缩侧索硬化症中的蛋白质聚集。
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