ECM2 and GLT8D2 in human pulmonary artery hypertension: fruits from weighted gene co-expression network analysis

Bai, Zeyang; Xu, Lian-Yan; Dai, Yue; Yuan, Qingchen; Zhou, Zihua

doi:10.21037/jtd-20-3069

Cited by 16 publications

(10 citation statements)

References 47 publications

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“…Most of these studies apply machine learning methods to simulate the progression of malignancy and find significant characteristics that are then used in a categorization scheme. According to the results of our study and those of other researchers [50][51][52][53][54][55][56], this was the first study in which analytical methods for identifying PAH biomarkers use many machine learning approaches, including RF, Lasso, SVM-RFE, and WGCNA. Akter et al [57] suggest that merging different machine learning algorithms may boost prediction performance and construct highly accurate diagnostic models.…”

Section: Discussionmentioning

confidence: 64%

FAM171B as a Novel Biomarker Mediates Tissue Immune Microenvironment in Pulmonary Arterial Hypertension

Luo

Yan

et al. 2022

Mediators of Inflammation

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The purpose of this study was to uncover potential diagnostic indicators of pulmonary arterial hypertension (PAH), evaluate the function of immune cells in the pathogenesis of the disease, and find innovative treatment targets and medicines with the potential to enhance prognosis. Gene Expression Omnibus was utilized to acquire the PAH datasets. We recognized differentially expressed genes (DEGs) and investigated their functions utilizing R software. Weighted gene coexpression network analysis, least absolute shrinkage and selection operators, and support vector machines were used to identify biomarkers. The extent of immune cell infiltration in the normal and PAH tissues was determined using CIBERSORT. Additionally, the association between diagnostic markers and immune cells was analyzed. In this study, 258DEGs were used to analyze the disease ontology. Most DEGs were linked with atherosclerosis, arteriosclerotic cardiovascular disease, and lung disease, including obstructive lung disease. Gene set enrichment analysis revealed that compared to normal samples, results from PAH patients were mostly associated with ECM-receptor interaction, arrhythmogenic right ventricular cardiomyopathy, the Wnt signaling pathway, and focal adhesion. FAM171B was identified as a biomarker for PAH ( area under the curve = 0.873 ). The mechanism underlying PAH may be mediated by nave CD4 T cells, resting memory CD4 T cells, resting NK cells, monocytes, activated dendritic cells, resting mast cells, and neutrophils, according to an investigation of immune cell infiltration. FAM171B expression was also associated with resting mast cells, monocytes, and CD8 T cells. The results suggest that PAH may be closely related to FAM171B with high diagnostic performance and associated with immune cell infiltration, suggesting that FAM171B may promote the progression of PAH by stimulating immune infiltration and immune response. This study provides valuable insights into the pathogenesis and treatment of PAH.

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Section: Discussionmentioning

confidence: 64%

FAM171B as a Novel Biomarker Mediates Tissue Immune Microenvironment in Pulmonary Arterial Hypertension

Luo

Yan

et al. 2022

Mediators of Inflammation

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“…This axis of the HIF pathway might maintain oxygen transport to appropriate levels in PNG highlanders while limiting the increase in haemoglobin concentration and blood viscosity. Moreover, five of the ten regions with the highest Fisher score include a gene associated with cardiovascular phenotypes (FBLN1 62 , GLT8D2 68 , DLGAP1 69 , PTPRG 70 and SLC24A4 71 ). This observation supports our hypothesis that selection in PNG highlanders acted on genes that might have helped them to counteract the hypoxic condition of their environment.…”

Section: Resultsmentioning

confidence: 99%

Positive selection in the genomes of two Papua New Guinean populations at distinct altitude levels

André

Brucato

Hudjasov

et al. 2022

Preprint

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Highlanders and lowlanders of Papua New Guinea (PNG) have faced distinct environmental conditions. These environmental differences lead to specific stress on PNG highlanders and lowlanders, such as hypoxia and environment-specific pathogen exposure, respectively. We hypothesise that these constraints induced specific selective pressures that shaped the genomes of both populations. In this study, we explored signatures of selection in newly sequenced whole genomes of 54 PNG highlanders and 74 PNG lowlanders. Based on multiple methods to detect selection, we investigated the 21 and 23 genomic top candidate regions for positive selection in PNG highlanders and PNG lowlanders, respectively. To identify the most likely candidate SNP driving selection in each of these regions, we computationally reconstructed allele frequency trajectories of variants in each of these regions and chose the SNP with the highest likelihood of being under selection with CLUES. We show that regions with signatures of positive selection in PNG highlanders genomes encompass genes associated with the hypoxia-inducible factors pathway, brain development, blood composition, and immunity, while selected genomic regions in PNG lowlanders contain genes related to immunity and blood composition. We found that several candidate driver SNPs are associated with haematological phenotypes in the UK biobank. Moreover, using phenotypes measured from the sequenced Papuans, we found that two candidate SNPs are significantly associated with altered heart rates in PNG highlanders and lowlanders. Furthermore, we found that 16 of the 44 selection candidate regions harboured archaic introgression. In four of these regions, the selection signal might be driven by the introgressed archaic haplotypes, suggesting a significant role of archaic admixture in local adaptation in PNG populations.

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“…The genes with high connectivity in the key modules were viewed as the hub genes ( 7 ), which were considered to play a more significant biological role in the gene regulatory network. Module membership (MM) was used to represent intramodular connectivity by correlating the gene expression profile with the ME of a given module ( 15 ). The closer the MM of a gene is to 1 or −1, the higher the connection to the given module ( 7 ).…”

Section: Methodsmentioning

confidence: 99%

Weighted gene co-expression network analysis identifies dysregulated B-cell receptor signaling pathway and novel genes in pulmonary arterial hypertension

Chen

Wang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundPulmonary arterial hypertension (PAH) is a devastating cardio-pulmonary vascular disease in which chronic elevated pulmonary arterial pressure and pulmonary vascular remodeling lead to right ventricular failure and premature death. However, the exact molecular mechanism causing PAH remains unclear.MethodsRNA sequencing was used to analyze the transcriptional profiling of controls and rats treated with monocrotaline (MCT) for 1, 2, 3, and 4 weeks. Weighted gene co-expression network analysis (WGCNA) was employed to identify the key modules associated with the severity of PAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological processes and pathways of key modules. Real-time PCR and western blot analysis were used to validate the gene expression. The hub genes were validated by an independent dataset obtained from the Gene Expression Omnibus database.ResultsA total of 26 gene modules were identified by WGCNA. Of these modules, two modules showed the highest correlation with the severity of PAH and were recognized as the key modules. GO analysis of key modules showed the dysregulated inflammation and immunity, particularly B-cell-mediated humoral immunity in MCT-induced PAH. KEGG pathway analysis showed the significant enrichment of the B-cell receptor signaling pathway in the key modules. Pathview analysis revealed the dysregulation of the B-cell receptor signaling pathway in detail. Moreover, a series of humoral immune response-associated genes, such as BTK, BAFFR, and TNFSF4, were found to be differentially expressed in PAH. Additionally, five genes, including BANK1, FOXF1, TLE1, CLEC4A1, and CLEC4A3, were identified and validated as the hub genes.ConclusionThis study identified the dysregulated B-cell receptor signaling pathway, as well as novel genes associated with humoral immune response in MCT-induced PAH, thereby providing a novel insight into the molecular mechanisms underlying inflammation and immunity and therapeutic targets for PAH.

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ECM2 and GLT8D2 in human pulmonary artery hypertension: fruits from weighted gene co-expression network analysis

Cited by 16 publications

References 47 publications

FAM171B as a Novel Biomarker Mediates Tissue Immune Microenvironment in Pulmonary Arterial Hypertension

FAM171B as a Novel Biomarker Mediates Tissue Immune Microenvironment in Pulmonary Arterial Hypertension

Positive selection in the genomes of two Papua New Guinean populations at distinct altitude levels

Weighted gene co-expression network analysis identifies dysregulated B-cell receptor signaling pathway and novel genes in pulmonary arterial hypertension

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