Integrated Analysis of Immunocyte Infiltration and Differential Gene Expression in Hypertrophic Obstructive Cardiomyopathy

Abstract Objective: Hypertrophic obstructive cardiomyopathy (HOCM) is one of the main reasons for sudden cardiac death (SCD) of young people. Researches have revealed that immune-related genes are closely relevant with HOCM. Therefore, it is important to explore the key immune regulatory mechanisms and biomarkers of HOCM.Methods: We used many bioinformatics methods, including linear models for microarray analysis (LIMMA), protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and CIBERSORT to assess the key pathway and hub genes involved in HOCM. Furthermore, expression levels of hub genes were validated in human tissue.Results: Our results showed that the degree of infiltration of five immune cells were linked to HOCM, including monocytes, macrophages M2, NK cell resting, B cells native, and T cells regulatory (Tregs). A total of 7 hub genes (CCL2, CXCL8, FOS, MAP2K1, NFKBIA, STAT3, and TNFRSF1A) were identified and validated by qt-PCR. The core genes including CCL2, MAP2K1, NFKBIA, STAT3, and TNFRSF1A are closely related to monocytes infiltration in HOCM.Conclusion: Taken together, our research will provide useful information to explore the immune mechanisms underlying HOCM and the potential targets for therapy. The candidate genes CCL2, MAP2K1, NFKBIA, STAT3, and TNFRSF1A were involved in the regulation of monocytes tissue infiltration, which is closely related to the HOCM.

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Identification of significant alteration genes, pathways and TFs induced by LPS in ARDS via bioinformatical analysis

BMC Infectious Diseases ◽

10.1186/s12879-021-06578-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Weina Lu ◽

Ran Ji

Keyword(s):

Expression Profiles ◽

Gene Expression Profiles ◽

Enrichment Analysis ◽

Receptor Interaction ◽

Integrated Analysis ◽

Pathway Enrichment Analysis ◽

Signal Pathways ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction

Abstract Background and aims Acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) is one of the most common acute thoracopathy with complicated pathogenesis in ICU. The study is to explore the differentially expressed genes (DEGs) in the lung tissue and underlying altering mechanisms in ARDS. Methods Gene expression profiles of GSE2411 and GSE130936 were available from GEO database, both of them included in GPL339. Then, an integrated analysis of these genes was performed, including gene ontology (GO) and KEGG pathway enrichment analysis in DAVID database, protein–protein interaction (PPI) network construction evaluated by the online database STRING, Transcription Factors (TFs) forecasting based on the Cytoscape plugin iRegulon, and their expression in varied organs in The Human Protein Atlas. Results A total of 39 differential expressed genes were screened from the two datasets, including 39 up-regulated genes and 0 down-regulated genes. The up-regulated genes were mainly enriched in the biological process, such as immune system process, innate immune response, inflammatory response, and also involved in some signal pathways, including cytokine–cytokine receptor interaction, Salmonella infection, Legionellosis, Chemokine, and Toll-like receptor signal pathway with an integrated analysis. GBP2, IFIT2 and IFIT3 were identified as hub genes in the lung by PPI network analysis with MCODE plug-in, as well as GO and KEGG re-enrichment. All of the three hub genes were regulated by the predictive common TFs, including STAT1, E2F1, IRF1, IRF2, and IRF9. Conclusions This study implied that hub gene GBP2, IFIT2 and IFIT3, which might be regulated by STAT1, E2F1, IRF1, IRF2, or IRF9, played significant roles in ARDS. They could be potential diagnostic or therapeutic targets for ARDS patients.

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Identification of Key Biomarkers Associated with Survival and Prognosis in Colon Adenocarcinoma

10.21203/rs.3.rs-444592/v1 ◽

2021 ◽

Author(s):

Yanjie Zhou ◽

Lu Jiang ◽

Jiang Lin ◽

Wendong Tang ◽

Wenqian Jiang ◽

...

Keyword(s):

Gene Expression ◽

Survival Analysis ◽

Protein Interaction ◽

Colon Adenocarcinoma ◽

High Rate ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Core Genes

Abstract Background: Colorectal cancer (CRC) has a high rate of relapse and recurrence that result in poor prognosis and unsatisfactory outcomes. Colon adenocarcinoma (COAD) is the most prevalent type of CRC. It is crucial to identify novel molecular biomarkers for the early diagnosis, prognosis evaluation and disease monitoring of COAD.Methods: Three gene expression profile data were downloaded from the Gene Expression Omnibus(GEO), and the differential expression genes(DEGs) were identified by GEO2R. Gene Ontology (GO) and KEGG pathway enrichment analysis were conducted by WebGestalt online tool. String database and Cytoscape software were used for protein–protein interaction (PPI) network construction and module analysis. The top 20 Hub Genes were screened from the PPI network using MCC algorithm on CytoHubba app of Cytoscape software, and were verified by ONCOMINE database then. The core genes affecting CRC prognosis were screened by GEPIA2 survival analysis web tool. Finally, the expression level and clinical indicators including core genes was analyzed by TCGA-COAD dataset.Results: In total, 413 differentially expressed genes (DEGs) were identified, and the GO and KEGG enrichment analyses of DEGs were processed. After, the protein–protein interaction (PPI) network was constructed and 20 hub genes were identified. Furthermore, three core genes were selected via survival analysis . Finally, the diagnostic and prognostic value of these core genes was verified by clinical analysis of TCGA-COAD dataset.Conclusion: SPP1, GRP and GNGT1 were all over-expressed in COAD, and may be regarded as novel diagnostic and prognostic biomarkers for COAD.

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Differential Expression of mRNAs in Peripheral Blood Related to Prodrome and Progression of Alzheimer’s Disease

BioMed Research International ◽

10.1155/2020/4505720 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Weishuang Xue ◽

Jinwei Li ◽

Kailei Fu ◽

Weiyu Teng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Peripheral Blood ◽

Bioinformatics Analysis ◽

Gene Expression Omnibus ◽

Venn Diagram ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Ppi Networks

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.

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The Screening and Identification of Key Biomarkers in Adrenocortical Carcinoma: Evidence from a Bioinformatics Analysis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2834 ◽

2022 ◽

Vol 12 (3) ◽

pp. 523-532

Author(s):

Xin Yan ◽

Chunfeng Liang ◽

Xinghuan Liang ◽

Li Li ◽

Zhenxing Huang ◽

...

Keyword(s):

Cell Cycle ◽

Gene Ontology ◽

Protein Interaction ◽

Adrenocortical Carcinoma ◽

Gene Expression Omnibus ◽

Heparin Binding ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Upregulated Genes

<sec> <title>Objective:</title> This study aimed to identify the potential key genes associated with the progression and prognosis of adrenocortical carcinoma (ACC). </sec> <sec> <title>Methods:</title> Differentially expressed genes (DEGs) in ACC cells and normal adrenocortical cells were assessed by microarray from the Gene Expression Omnibus database. The biological functions of the classified DEGs were examined by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein–protein interaction (PPI) network was mapped using Cytoscape software. MCODE software was also used for the module analysis and then 4 algorithms of cytohubba software were used to screen hub genes. The overall survival (OS) examination of the hub genes was then performed by the ualcan online tool. </sec> <sec> <title>Results:</title> Two GSEs (GSE12368, GSE33371) were downloaded from GEO including 18 and 43 cases, respectively. One hundred and sixty-nine DEGs were identified, including 57 upregulated genes and 112 downregulated genes. The Gene Ontology (GO) analyses showed that the upregulated genes were significantly enriched in the mitotic cytokines is, nucleus and ATP binding, while the downregulated genes were involved in the positive regulation of cardiac muscle contraction, extracellular space, and heparin-binding (P < 0.05). The Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway examination showed significant pathways including the cell cycle and the complement and coagulation cascades. The protein– protein interaction (PPI) network consisted of 162 nodes and 847 edges, including mitotic nuclear division, cytoplasmic, protein kinase binding, and cell cycle. All 4 identified hub genes (FOXM1, UBE2C, KIF11, and NDC80) were associated with the prognosis of adrenocortical carcinoma (ACC) by survival analysis. </sec> <sec> <title>Conclusions:</title> The present study offered insights into the molecular mechanism of adrenocortical carcinoma (ACC) that may be beneficial in further analyses. </sec>

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Weighted gene co-expression network analysis to define pivotal modules and genes in diabetic heart failure

Bioscience Reports ◽

10.1042/bsr20200507 ◽

2020 ◽

Vol 40 (7) ◽

Author(s):

Weiwei Liang ◽

FangFang Sun

Keyword(s):

Heart Failure ◽

Kegg Pathway ◽

Diabetic Heart ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Light Yellow ◽

Go Enrichment ◽

Key Genes ◽

Functional Analyses

Abstract This research was carried out to reveal specific hub genes involved in diabetic heart failure, as well as remarkable pathways that hub genes locate. The GSE26887 dataset from the GEO website was downloaded. The gene co-expression network was generated and central modules were analyzed to identify key genes using the WGCNA method. Functional analyses were conducted on genes of the clinical interest modules via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene ontology (GO) enrichment, associated with protein–protein interaction (PPI) network construction in a sequence. Centrality parameters of the PPI network were determined using the CentiScape plugin in Cytoscape. Key genes, defined as genes in the ≥95% percentile of the degree distribution of significantly perturbed networks, were identified. Twenty gene co-expression modules were detected by WGCNA analysis. The module marked in light yellow exhibited the most significant association with diabetes (P=0.08). Genes involved in this module were primarily located in immune response, plasma membrane and receptor binding, as shown by the GO analysis. These genes were primarily assembled in endocytosis and phagosomes for KEGG pathway enrichment. Three key genes, STK39, HLA-DPB1 and RAB5C, which may be key genes for diabetic heart failure, were identified. To our knowledge, our study is the first to have constructed the co-expression network involved in diabetic heart failure using the WGCNA method. The results of the present study have provided better understanding the molecular mechanism of diabetic heart failure.

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Identification of critical genes and pathways involved in intervertebral disc degeneration (IDD) An integrated bioinformatics analysis

10.21203/rs.3.rs-32656/v1 ◽

2020 ◽

Author(s):

Jingyang Zhou ◽

Feng Xin ◽

Chuyu Xiao ◽

Wuyuan Zhou

Keyword(s):

Daily Life ◽

Vital Role ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Diagnosis And Prognosis ◽

Study Results ◽

Validation Experiment ◽

The One

Abstract Background: In western countries and China, back and neck pain has become a common problem that bothers daily life and severely influences the quality of our daily life. Among all factors that lead to chronic neck and back pain, IDD is the one that couldn’t be easily neglected. Methods: This study aims to figure out the critical genes and pathways involved in the development of IDD and provide a new aspect of following investigations on the etiology of IDD. We firstly systemically searched the GEO database and identified the differentially expressed genes (DEGs) from the expression profile dataset we selected. We secondly constructed the protein-protein interaction (PPI) network for DEGs, identified the top ten hub genes from the whole PPI network and found two statically and medically significant modules from the network, we then performed the GO and KEGG analysis on the DEGs, top ten hub genes, the PPI network and the two statically and medically modules. In the end, we provided the primers of the mRNAs of all DEGs, which will be useful for the validation experiment of this study. Results: FN1, MMP2, POSTN, COL3A1, TIMP3, FBN1, GJA1, TGFBI, EFEMP1 and ID1 were top ten hub genes identified from this study, and they may play a vital role in the development of IDD. Angiogenesis and integrin binging are crucial biological process and molecular function defined in this study, which are worthy of being intensely investigated.Conclusion: More studies on the top ten hub genes, the role of angiogenesis and integrin binding in IDD are urgently needed, which will benefit the prevention, screening, diagnosis and prognosis of IDD.

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Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

Frontiers in Genetics ◽

10.3389/fgene.2020.614195 ◽

2021 ◽

Vol 11 ◽

Author(s):

Miao Xu ◽

Tianxiang Ouyang ◽

Kaiyang Lv ◽

Xiaorong Ma

Keyword(s):

Differential Expression ◽

Enrichment Analysis ◽

Infantile Hemangioma ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Normal Tissues ◽

Network Analyses ◽

Cycle Arrest ◽

Auc Value

BackgroundInfantile hemangioma (IH) is characterized by proliferation and regression.MethodsBased on the GSE127487 dataset, the differentially expressed genes (DEGs) between 6, 12, or 24 months and normal samples were screened, respectively. STEM software was used to screen the continued up-regulated or down-regulated in common genes. The modules were assessed by weighted gene co-expression network analysis (WGCNA). The enrichment analysis was performed to identified the biological function of important module genes. The area under curve (AUC) value and protein-protein interaction (PPI) network were used to identify hub genes. The differential expression of hub genes in IH and normal tissues was detected by qPCR.ResultsThere were 5,785, 4,712, and 2,149 DEGs between 6, 12, and 24 months and normal tissues. We found 1,218 DEGs were up-regulated or down-regulated expression simultaneously in common genes. They were identified as 10 co-expression modules. Module 3 and module 4 were positively or negatively correlated with the development of IH, respectively. These two module genes were significantly involved in immunity, cell cycle arrest and mTOR signaling pathway. The two module genes with AUC greater than 0.8 at different stages of IH were put into PPI network, and five genes with the highest degree were identified as hub genes. The differential expression of these genes was also verified by qRTPCR.ConclusionFive hub genes may distinguish for proliferative and regressive IH lesions. The WGCNA and PPI network analyses may help to clarify the molecular mechanism of IH at different stages.

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Using Weighted Gene Co-Expression Network Analysis to Identify Key Genes Related to the Onset of Preeclampsia

10.21203/rs.3.rs-87182/v1 ◽

2020 ◽

Author(s):

Xinyang Shen ◽

Zhijian Wang ◽

Zhirui Zeng ◽

Zhenqin Huang ◽

Xiaowei Huang ◽

...

Keyword(s):

Enrichment Analysis ◽

Diagnostic Value ◽

Functional Enrichment ◽

Immune Response Gene ◽

Control Group ◽

Ppi Network ◽

Hub Genes ◽

Ontology Term ◽

Gene Data ◽

Core Genes

Abstract Background: Preeclampsia is a form of hypertension in pregnancy, which induced by complicated factors. However, the pathogenesis of the disease is unclear. The present study was aimed to discover the critical biomarkers associated with the occurrence and development of preeclampsia. Methods：Gene data profile GSE75010 was downloaded from the Gene Expression Omnibus (GEO) database and used as discovery cohort to establish a WGCNA network determining significant modules which associated with clinical traits. Subsequently, functional enrichment analysis, pathway analysis and protein-protein interaction (PPI) network construction were performed on the core genes in significant modules to identify hub genes. Then, gene data profile GSE25906 was used as verified cohort to determine their diagnostic value of hub genes. The protein expression levels of these hub genes in preeclampsia and control placental tissues were verified using immunohistochemistry method. Finally, GSEA was performed to analyze their enrichment pathways. Results: Total 33 co-expression modules were identified after the establishment of WGCNA, of which 4 gene modules were identified as significant modules because they were related to multiple (>3) clinical traits. Total 75 core genes in significant modules were analyzed, and results showed that they were mainly enriched in adaptive immune response (Gene Ontology term) and platelet activation (Kyoto Encyclopedia of Genes and Genomes term). Finally, a total of 5 genes including TYROBP, PLEK, LCP2, HCK, ITGAM were identified as hub genes which scored high in PPI network and had high diagnostic value. Furthermore, the protein level of these 5 genes in placental tissues of preeclampsia was lower than that of the control group. Moreover, these 5 genes were all enriched in 17 pathways, including autoimmunity pathway. Conclusions：These 5 genes (TYROBP, PLEK, LCP2, HCK, ITGAM) may be closely related to the pathogenesis of preeclampsia, which may also help the diagnosis and therapy of preeclampsia.

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Bioinformatics Approach to Identify Common Gene Signatures of Patients With Coronavirus 2019 and Lung Adenocarcinoma

10.21203/rs.3.rs-880952/v1 ◽

2021 ◽

Author(s):

Xiao Liang ◽

Yali Chen ◽

Yuchao Fan

Keyword(s):

Lung Adenocarcinoma ◽

Severe Disease ◽

Enrichment Analysis ◽

Immune Checkpoints ◽

Specific Gene ◽

Ppi Network ◽

Hub Genes ◽

Immune Infiltration ◽

Protein Protein Interaction ◽

Tf Gene

Abstract Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman’s correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), cellular component (CC) as well as to pathways, specific organs, cells and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.

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Overexpression of SKA Complex Is Associated With Poor Prognosis in Gliomas

Frontiers in Neurology ◽

10.3389/fneur.2021.755681 ◽

2022 ◽

Vol 12 ◽

Author(s):

Shoukai Yu

Keyword(s):

Chromosome Segregation ◽

Poor Prognosis ◽

Nuclear Division ◽

Prognostic Significance ◽

Mrna Levels ◽

Ppi Network ◽

Hub Genes ◽

Protein Protein Interaction ◽

Spindle Microtubules

The spindle and kinetochore-associated complex is composed of three members: SKA1, SKA2, and SKA3. It is necessary for stabilizing spindle microtubules attaching to kinetochore (KT) in the middle stage of mitosis. The SKA complex is associated with poor prognosis in several human cancers. However, the role of SKA complex in rare malignant diseases, such as gliomas, has not been fully investigated. We investigated several databases, including Oncomine, UALCAN, and cBioPortal to explore the expression profile and prognostic significance of SKA complex in patients with gliomas. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathways were used to analyze the potential enriched pathways. The genes co-expressed with SKA complex were identified and used for developing a protein-protein interaction (PPI) network using the STRING database. We found a significant overexpression of the mRNA levels of SKA1, SKA2, and SKA3 in patients with glioma patients. Higher expression of SKA1 and SKA3, but not SKA2, was significantly correlated with shorter overall survival of patients with glioma. In glioma, SKA complex was found to be involved in nuclear division, chromosome segregation, and DNA replication. The results of PPI network identified 10 hub genes (CCNB2, UBE2C, BUB1B, TPX2, CCNA2, CCNB1, MELK, TOP2A, PBK, and KIF11), all of which were overexpressed and negatively associated with prognosis of patients with glioma. In conclusion, our study sheds new insights into the biological role and prognostic significance of SKA complex in glioma.

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