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Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

ABSTRACT: The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable causes of acute lymphocytopenia at the onset of severe/critical conditions. Comparison of the transcriptomes of the bronchoalveolar microenvironment and peripheral blood indicates alveolar macrophages, alveolar epithelial cells, and monocytes in lungs as the potential main sources of elevated cytokines mediating systemic immune responses and organ damages. In addition, the transcriptomes of patient blood cells are characterized by distinct gene regulatory networks and alternative splicing events. Our study provides a panorama of the host responses in COVID-19, which may serve as the basis for developing further diagnostics and therapy.

SUBMITTER: Tan Y

PROVIDER: S-EPMC8185699 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

Tan Yun Y Zhang Wei W Zhu Zhaoqin Z Qiao Niu N Ling Yun Y Guo Mingquan M Yin Tong T Fang Hai H Xu Xiaoguang X Lu Gang G Zhang Peipei P Yang Shuangshuang S Fu Ziyu Z Liang Dongguo D Xie Yinyin Y Zhang Ruihong R Jiang Lu L Yu Shuting S Lu Jing J Jiang Fangying F Chen Jian J Xiao Chenlu C Wang Shengyue S Chen Shuo S Bian Xiu-Wu XW Lu Hongzhou H Liu Feng F Chen Saijuan S

Cell discovery 20210608 1

The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable ca ...[more]

PMID: 34103487

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Project description:BackgroundPhoebe zhennan S.Lee (nanmu) is listed as a threatened tree species in China, whose growth and development, especially during the seedling stage, can be severely limited by drought. Previous studies on nanmu responses to drought stress involved physiological and biochemical analyses, while the molecular mechanisms remained unclear. Therefore, it is of great significance to carry out molecular biology research on the drought resistance of nanmu and reveal the genetic background and molecular regulation mechanism of nanmu drought resistance.ResultsDrought stress enhanced the soluble sugar (SS), free proline(PRO), superoxide anion (O2·-), and hydrogen peroxide (H2O2) contents as well as the peroxidase (POD) and monodehydroascorbate reductase (MDHAR) activities of nanmu. However, glutathione S-transferase (GST) activity was sensitive to drought stress. Further transcriptomic and proteomic analyses revealed the abundant members of the differentially expressed genes(DEGs) and differentially expressed proteins(DEPs) that were related to phenylpropanoid and flavonoid biosynthesis, hormone biosynthesis and signal transduction, chlorophyll metabolism, photosynthesis, and oxidation-reduction reaction, which suggested their involvement in the drought response of nanmu. These enhanced the osmotic regulation, detoxification, and enzyme-induced and non-enzyme-induced antioxidant ability of nanmu. Moreover, 52% (447/867) of proteins that were up-regulated and 34% (307/892) down-regulated ones were attributed to the increase and decrease of transcription abundance. Transcript up (TU) and protein up (PU) groups had 447 overlaps, while transcript down (TD) and protein down (PD) groups had 307 overlaps, accounting for 54% of up and 35% of down-regulated proteins. The lack of overlap between DEGs and DEPs also suggested that post-transcriptional regulation has a critical role in nanmu response to drought.ConclusionsOur research results provide significant insights into the regulatory mechanisms of drought stress in nanmu.

Project description:Ischemic stroke (IS), a leading cause of global disability and mortality, is characterized by white matter damage and demyelination. Despite advances, the molecular mechanisms driving post-IS myelin pathology remain poorly understood, limiting therapeutic development. This study investigates key myelin-related genes (MRGs) and their regulatory networks to identify novel therapeutic targets. A transient middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice, with brain tissues collected at four timepoints (Sham0D, MCAO0D, MCAO7D, MCAO14D). Transcriptomic and proteomic sequencing were performed, followed by soft clustering (Mfuzz), functional enrichment (GO/KEGG), and ROC analysis to identify key MRGs. Competing endogenous RNA (ceRNA) networks were constructed, and drug prediction was conducted using the Comparative Toxicogenomics Database (CTD) and molecular docking. Expression validation was performed via qRT-PCR and Western blot. Integrated multi-omics analysis identified Wasf3 and Slc25a5 as key MRGs, enriched in mitochondrial respiration, calcium metabolism, and cytoskeletal regulation. The AUC values of the one-to-one model scores were all greater than 0.7, suggesting that Wasf3 and Slc25a5 were able to effectively discriminate between samples from different time points. A ceRNA network revealed critical interactions, including the Wasf3-mmu-miR-423-5p-H19 axis, linking apoptosis and myelin dysfunction. Drug prediction highlighted valproic acid (VPA) as a high-affinity binder for both genes (binding energies: - 4.2 and - 4.7 kcal/mol), suggesting its potential as a therapeutic candidate for IS. Experimental validation confirmed significant downregulation of Wasf3 mRNA (p < 0.01) and protein (p = 0.069) post-IS, while Slc25a5 showed no significant changes, potentially due to sample size limitations. This study establishes Wasf3 and Slc25a5 as pivotal regulators of post-IS myelin pathology and proposes VPA as a promising therapeutic candidate to enhance remyelination. The findings underscore the utility of multi-omics approaches in bridging molecular mechanisms to clinical translation, offering new strategies for IS diagnosis and treatment.

Dataset Information

Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

Publications

Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

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