Exploring the "gene-protein-metabolite" network of coronary heart disease with phlegm and blood stasis syndrome by integrated multi-omics strategy.
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ABSTRACT:
SUBMITTER: Yang G
PROVIDER: S-EPMC9744761 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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Exploring the "gene-protein-metabolite" network of coronary heart disease with phlegm and blood stasis syndrome by integrated multi-omics strategy.
Yang Guang G Zhou Siyuan S He Haoqiang H Shen Zinuo Z Liu Yongmei Y Hu Jun J Wang Jie J
Frontiers in pharmacology 20221129
<b>Background:</b> According to the theory of traditional Chinese medicine, phlegm and blood stasis (PBS) is the pathological basis for coronary heart disease (CHD). This study aimed to explore the biological basis of PBS syndrome in CHD. <b>Methods:</b> Using a strategy that integrated RNA-seq, DIA-based proteomics, and untargeted metabolomics on 90 clinic samples, we constructed a "gene-protein-metabolite" network for CHD-PBS syndrome. We expanded the sample size and validated the differential ...[more]
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Project description:Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.
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| S-EPMC4129150 | biostudies-literature
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Project description:Gene function can be described using various measures. We integrated association studies of three types of omics data to provide insights into the pathophysiology of subclinical coronary disease and myocardial infarction (MI). Using multivariable regression models, we associated: (1) single nucleotide polymorphism, (2) DNA methylation, and (3) gene expression with coronary artery calcification (CAC) scores and MI. Among 3106 participants of the Framingham Heart Study, 65 (2.1%) had prevalent MI and 60 (1.9%) had incident MI, median CAC value was 67.8 [IQR 10.8, 274.9], and 1403 (45.2%) had CAC scores > 0 (prevalent CAC). Prevalent CAC was associated with AHRR (linked to smoking) and EXOC3 (affecting platelet function and promoting hemostasis). CAC score was associated with VWA1 (extracellular matrix protein associated with cartilage structure in endomysium). For prevalent MI we identified FYTTD1 (down-regulated in familial hypercholesterolemia) and PINK1 (linked to cardiac tissue homeostasis and ischemia-reperfusion injury). Incident MI was associated with IRX3 (enhancing browning of white adipose tissue) and STXBP3 (controlling trafficking of glucose transporter type 4 to plasma). Using an integrative trans-omics approach, we identified both putatively novel and known candidate genes associated with CAC and MI. Replication of findings is warranted.
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Project description:Objective:The purpose of the study was to form a questionnaire of expert consensus about phlegm turbidity syndrome of coronary heart disease (CHD) using literature method and Delphi method, which could provide the objective evidences for the clinical diagnosis and treatment for CHD. Method:The CBM, CNKI, VIP, and PubMed were searched. The articles about phlegm turbidity syndrome for CHD with the definite related four diagnostic data were included. Based on the results of the literature method, two rounds of Delphi method were conducted. The TCM experts about CHD were enrolled. Concentration and coordination index of the experts were used to select the items. Results:Literature method: A total of 118 articles were included. Greasy fur, slippery pulse, chest fullness or chest pain, anorexia, nausea and vomiting, vertigo, excessive phlegm, abdominal fullness, head heaviness, obesity, stringy pulse, physical heaviness, soft pulse, somnolence, fatigue, and pale tongue (16 items) had the relatively high proportion, and they were eligible for Delphi process. Delphi method: A total of 93 experts (22 for the first round, 71 for the second round) were included. The reliability of the items was 0.885 for all the experts. The 16 items were not significantly different between the two rounds (P>0.05). According to the results of mean, frequency, sum of ranks and coefficient of variation, the item of nausea and vomiting, somnolence, pale tongue, and soft pulse were deleted. Conclusions:The questionnaire of phlegm turbidity syndrome of CHD was established, with good reliability. The sensitivity and specificity of the questionnaire are still necessary to further validate for clinical or scientific use.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2024-09-05 | GSE254297 | GEO
Project description:Integrated multi-omics analysis
| PRJNA1069651 | ENA
Project description:Chaihu-Shugan-San (CHSGS), a noted traditional Chinese medicine formula, has been used as a complementary and alternative therapy for liver fibrosis. However, the antifibrotic mechanisms of CHSGS still remain unclear. Thus, we used network pharmacology approach in combination with single cell and bulk transcriptomics to elucidate the antifibrotic mechanisms of CHSGS. We first screened out 134 bioactive ingredients of CHSGS through the defined criteria. Then, 1150 genes were predicted to be targets for CHSGS, while 625 liver fibrosis-associated genes were identified by single cell transcriptomics analysis. Next, 71 intersecting genes of CHSGS and liver fibrosis were defined as the therapeutic targets in CHSGS against liver fibrosis. Further, 21 core targets and 12 core ingredients of CHSGS against liver fibrosis were also identified. Meanwhile, enrichment analyses of core targets highlighted that the key mechanisms of CHSGS against liver fibrosis include modulation of inflammation responses, inhibition of angiogenesis, and regulation of ECM remodeling, of which the most important mechanism was the regulation of ECM remodeling. The molecular docking simulation validated strong binding affinity between the core targets and core ingredients. Furthermore, 62-gene signature may be used for determining the prognosis in cirrhotic patients based on the results of ssGSEA-Cox analysis. In conclusion, the present study revealed the multiple pharmacological targets and therapeutic mechanisms of CHSGS against liver fibrosis, which may thus serve as an effective antifibrotic therapy. Meanwhile, CHSGS may improve survival of patients with liver cirrhosis by the interaction of 62-gene signature.
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