scholarly journals Proteomic Analysis of ISGylation in Immortalized Porcine Alveolar Macrophage Cell Lines Induced by Type I Interferon

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 164
Author(s):  
Chengbo Zhu ◽  
Jingrui Li ◽  
Chaonan Tian ◽  
Mengmeng Qin ◽  
Zhenni Wang ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Type I Interferons ◽  
Porcine Alveolar Macrophage ◽  
Type I ◽  
Functional Roles ◽  
Protein Protein Interaction ◽  
Network Analyses ◽  
Novel Host ◽  
Regulatory Loop

Interferon-stimulated gene product 15 (ISG15), a ubiquitin-like molecule, can be conjugated to protein substrates through a reversible process known as ISGylation. ISG15 and ISGylation are both strongly upregulated by type I interferons and play putative key roles in host innate immunity against viral infection. However, the function of ISGylation and identities of ISGylation substrates are largely unknown. Here, a novel monoclonal antibody (Mab) that specifically recognizes porcine ISG15 (pISG15) was employed to capture ISG15-conjugated proteins from IFNs-stimulated porcine cell lysates. Next, Mab-captured conjugates were analyzed using proteomics-based tools to identify potential ISGylation protein targets in order to elucidate the roles of ISG15 and ISGylation in porcine cells. Subsequently, 190 putative ISGylation sites were detected within 98 identified ISGylation candidates; several candidates contained more than one ISGylation-modifiable lysine residue, including pISG15 itself. Motif enrichment analysis of confirmed ISGylation sites demonstrated a moderate bias towards certain sites with specific upstream amino acid residues. Meanwhile, results of Gene Ontology (GO)-based annotation and functional enrichment and protein-protein interaction (PPI) network analyses of porcine ISG15-conjugated substrate proteins indicated that these substrates were mainly associated with the host metabolism, especially nucleotide metabolic pathways that ultimately may participate in cellular antiviral defenses. Notably, several ISGs (MX1, IFIT1, OAS1, ISG15 and putative ISG15 E3 ligase Herc6) were also identified as putative ISGylation substrates within a regulatory loop involving ISGylation of ISGs themselves. Taken together, proteomics analysis of porcine ISGylation substrates revealed putative functional roles of ISG15 and novel host ISGylation targets that may ultimately be involved in cellular antiviral responses.

scholarly journals Bioinformatic analysis identifies potential key genes of epilepsy

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0254326
Author(s):  
Yike Zhu ◽  
Dan Huang ◽  
Zhongyan Zhao ◽  
Chuansen Lu
Keyword(s):  
Network Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
P Value ◽  
Ppi Network ◽  
Functional Roles ◽  
Protein Protein Interaction

Background Epilepsy is one of the most common brain disorders worldwide. It is usually hard to be identified properly, and a third of patients are drug-resistant. Genes related to the progression and prognosis of epilepsy are particularly needed to be identified. Methods In our study, we downloaded the Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE143272. Differentially expressed genes (DEGs) with a fold change (FC) >1.2 and a P-value <0.05 were identified by GEO2R and grouped in male, female and overlapping DEGs. Functional enrichment analysis and Protein-Protein Interaction (PPI) network analysis were performed. Results In total, 183 DEGs overlapped (77 ups and 106 downs), 302 DEGs (185 ups and 117 downs) in the male dataset, and 750 DEGs (464 ups and 286 downs) in the female dataset were obtained from the GSE143272 dataset. These DEGs were markedly enriched under various Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. 16 following hub genes were identified based on PPI network analysis: ADCY7, C3AR1, DEGS1, CXCL1 in male-specific DEGs, TOLLIP, ORM1, ELANE, QPCT in female-specific DEGs and FCAR, CD3G, CLEC12A, MOSPD2, CD3D, ALDH3B1, GPR97, PLAUR in overlapping DEGs. Conclusion This discovery-driven study may be useful to provide a novel insight into the diagnosis and treatment of epilepsy. However, more experiments are needed in the future to study the functional roles of these genes in epilepsy.

scholarly journals Proteomic Analysis of the Secretome and Exosomes of Feline Adipose-Derived Mesenchymal Stem Cells

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 295
Author(s):  
Antonio J. Villatoro ◽  
María del Carmen Martín-Astorga ◽  
Cristina Alcoholado ◽  
María del Mar Sánchez-Martín ◽  
José Becerra
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Endocrine System ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Bioactive Molecules ◽  
Protein Protein Interaction ◽  
Cell Signaling Pathways

Mesenchymal stem cells (MSCs) have been shown to have therapeutic efficacy in different complex pathologies in feline species. This effect is attributed to the secretion of a wide variety of bioactive molecules and extracellular vesicles, such as exosomes, with significant paracrine activity, encompassed under the concept of the secretome. However, at present, the exosomes from feline MSCs have not yet been studied in detail. The objective of this study is to analyze and compare the protein profiles of the secretome as a whole and its exosomal fraction from feline adipose-derived MSCs (fAd-MSCs). For this, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein–Protein Interaction Networks Functional Enrichment Analysis (STRING) were utilized. A total of 239 proteins were identified in the secretome, and 228 proteins specific to exosomes were identified, with a total of 133 common proteins. The proteins identified in the secretome were located in the extracellular regions and in the cytoplasm, while the exosomal proteins were located mainly in the membrane, cytoplasm and cytosol. Regarding function, in the secretome, proteins involved in different metabolic pathways, in pathways related to the immune system and the endocrine system and in the processing of proteins in the endoplasmic reticulum predominated. In contrast, proteins specific to exosomes were predominantly associated with endocytosis, cell junctions, platelet activation and other cell signaling pathways. The possible future use of the secretome, or some of its components, such as exosomes, would provide a non-cell-based therapeutic strategy for the treatment of different diseases that would avoid the drawbacks of cell therapy.

scholarly journals Identifcation of The Ferroptosis-Related Gene Signature In Placenta of Patients With Early-Onset Preeclampsia

2021 ◽  
Author(s):  
Nana Yang ◽  
Qianghua Wang ◽  
Biao Ding ◽  
Yinging Gong ◽  
Yue Wu ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Late Onset ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Network Analyses

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

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

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.

scholarly journals Co-expression network analysis identifies specific hub genes in association with developmental neuronal remodeling in Drosophila melanogaster

2019 ◽  
Author(s):  
Yunze Liu ◽  
Xiaojie Sun ◽  
Aijun Qu
Keyword(s):  
Drosophila Melanogaster ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Neuronal Remodeling ◽  
Gene Modules

As an evolutionarily conserved mechanism, developmental neuronal remodeling is needed for the proper wiring of the nervous system and is critical for understanding the neurodevelopment mechanisms. Previous studies have shown that during metamorphosis lots of Drosophila melanogaster mushroom body neurons experience stereotypic remodeling. However, the related regulators and downstream executors of pathways are yet unclear, especially studies of transcriptional gene co-expression analysis of nervous systems remain insufficient. In this study, we develop a weighted gene co-expression network (WGCNA) to classify gene modules associated with neuronal remodeling. Moreover, functional and pathway enrichment analysis with protein-protein network construction is applied to detect high informative hub genes in the targeted gene module. Thus, we select a total of five hub genes that play critical roles in neuronal remodeling and identify them with functional enrichment analysis and protein-protein interaction network. Overall, this study provides insight into the underlying molecular mechanism of developmental neuronal remodeling in Drosophila melanogaster.

scholarly journals Apolipoprotein B Is Associated With the Microenvironment of Cholangiocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaofeng Xu ◽  
Diyu Chen ◽  
Xiaode Feng ◽  
Jiating Hu ◽  
Jiangzhen Ge ◽  
...  
Keyword(s):  
Immune Cells ◽  
Apolipoprotein B ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Abundance Ratio ◽  
Functional Enrichment ◽  
Score System ◽  
Protein Protein Interaction ◽  
New Ideas ◽  
Differential Expressed Genes

BackgroundCholangiocarcinoma (CCA) is a kind of devastating malignancy, which is correlated with the extremely high mortality. Due to the occult pathogenesis of CCA, most patients are diagnosed in the advanced stage. However, the efficacy of chemotherapy and immunotherapy is limited for these patients. The cause for this phenomenon is unclear, the recent researches indicate that it could be related to predisposing genetic factors and tumor microenvironment (TME) changes. The TME is created by the tumor and dominated by tumor-induced interactions. And the tumor prognosis could be influenced by the extent of infiltrating immune cells and stromal cells in TME.Materials and methodsThe abundance ratio of immune cells for each sample was obtained via the CIBERSORT algorithm, and we used ESTIMATE score system to calculate the immune and stromal scores in CCA. The CCA cases in TCGA database were categorized into high and low score groups according to their immune/stromal scores. And then, we identified the differential expressed genes (DEGs) in two groups. Functional enrichment analysis and protein‐protein interaction networks were carried out for DEGs. Interestingly, we found out that apolipoprotein B (APOB) is the most down-regulated among these genes. Then we performed the immunohistochemistry staining of APOB in a CCA tumor microarray which contained 100 CCA cases, APOB was down-regulated in CCA samples. Thus, we evaluated the APOB function in the TME of CCA through TIMER.Results and ConclusionThe results demonstrate that the infiltration degree of immune cells in CCA could be influenced by the expression of APOB, and the APOB expression could be mediated by DNA methylation. Our study not only indicates APOB is a potential target for CCA immunotherapy but also provides new ideas for researchers to explore the immunotherapy of various tumors.

scholarly journals Co-expression network analysis identifies specific hub genes in association with developmental neuronal remodeling in Drosophila melanogaster

2019 ◽  
Author(s):  
Yunze Liu ◽  
Xiaojie Sun ◽  
Aijun Qu
Keyword(s):  
Drosophila Melanogaster ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Neuronal Remodeling ◽  
Gene Modules

As an evolutionarily conserved mechanism, developmental neuronal remodeling is needed for the proper wiring of the nervous system and is critical for understanding the neurodevelopment mechanisms. Previous studies have shown that during metamorphosis lots of Drosophila melanogaster mushroom body neurons experience stereotypic remodeling. However, the related regulators and downstream executors of pathways are yet unclear, especially studies of transcriptional gene co-expression analysis of nervous systems remain insufficient. In this study, we develop a weighted gene co-expression network (WGCNA) to classify gene modules associated with neuronal remodeling. Moreover, functional and pathway enrichment analysis with protein-protein network construction is applied to detect high informative hub genes in the targeted gene module. Thus, we select a total of five hub genes that play critical roles in neuronal remodeling and identify them with functional enrichment analysis and protein-protein interaction network. Overall, this study provides insight into the underlying molecular mechanism of developmental neuronal remodeling in Drosophila melanogaster.

scholarly journals Gene Clusters Based on OLIG2 and CD276 Could Distinguish Molecular Profiling in Glioblastoma

2021 ◽  
Author(s):  
Minjie Fu ◽  
Jinsen Zhang ◽  
Weifeng Li ◽  
Shan He ◽  
Jingwen Zhang ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Efficient Method ◽  
Enrichment Analysis ◽  
Gene Clusters ◽  
Functional Enrichment Analysis ◽  
Molecular Classification ◽  
Functional Enrichment ◽  
Protein Protein Interaction ◽  
Dna Elements

Abstract BackgroundThe molecular classification of glioblastoma (GBM) based on transcriptomic analysis could provide precise treatment and prognosis. However, current subtyping (Classic, Mesenchymal, Neural, Proneural) is a time-consuming and cost-intensive process, which hinders its clinical application. A simple and efficient method for classification was imperative.MethodsRandom forest algorithm was applied to conduct a gene cluster featured with hub genes, OLIG2 and CD276. Functional enrichment analysis and Protein-protein interaction were performed using the genes in this gene cluster. The classification efficiency of the gene cluster was validated by WGCNA and LASSO algorithms, and tested in GSE84010 and Gravandeel’s GBM datasets. ResultsThe gene cluster (n = 26) could distinguish mesenchymal and proneural excellently (AUC = 0.92), which could be validated by multiple algorithms (WGCNA, LASSO) and datasets (GSE84010 and Gravandeel’s GBM dataset). The gene cluster could be functionally enriched in DNA elements and T cell associated pathways. Additionally, five genes in the signature could predict the prognosis well (p = 0.0051 for training cohort, p = 0.065 for test cohort). ConclusionsThis study proved the accuracy and efficiency of random forest classifier for GBM subtyping and provided a convenient and efficient method for subtyping Proneural and Mesenchymal GBM.

scholarly journals Role of COL3A1 and POSTN on Pathologic Stages of Esophageal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382097748
Author(s):  
Shao-wei Zhang ◽  
Nan Zhang ◽  
Na Wang
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Protein Protein Interaction ◽  
And Control ◽  
The Impact

Background: Esophageal cancer (EC) is a primary malignant tumor originating from the esophageal of the epithelium. Surgical resection is a potential treatment for EC, but this is only appropriate for patients who have locally resectable lesions suitable for surgery. However, most patients with EC are at a late stage when diagnosed. Therefore, there is an urgent need to further explore the pathogenesis of EC to enable early diagnosis and treatment. Methods: Our study downloaded 2 expression spectrum datasets (GSE92396 and GSE100942) in the Gene Expression Omnibus (GEO) database. GEO2 R was used to identify the Differentially expressed genes (DEGs) between the samples of EC and control. Using the DAVID tool to make the Functional enrichment analysis. Constructing A protein–protein interaction (PPI) network. Identifying the Hub genes. The impact of hub gene expression on overall survival and their expression based on immunohistochemistry were analyzed. Associated microRNAs were also predicted. Results: There were 36 common DEGs identified. The analysis of GO and KEGG results shown that the variations were predominantly concentrated in the extracellular matrix (ECM), ECM organization, DNA binding, platelet activation, and ECM-receptor interactions. COL3A1 and POSTN had high expression in EC tissues which was compared with their expression in healthy tissues. Analysis of pathologic stages showed that when COL3A1 and POSTN were highly expressed, the stage of the pathologic of EC patients was relatively high (P < 0.005). Conclusions: COL3A1 and POSTN may play an important role in the advancement and occurrence of EC. These genes could provide some novel ideas and basis for the diagnosis and targeted treatment of EC.

Identification Of Putative Gene Signatures Associated With Diagnosis And Prognosis Of Breast Cancer

2021 ◽  
Vol 44 (3) ◽  
pp. E45-54
Author(s):  
Chao Tan ◽  
Fang Zuo ◽  
Mingqian Lu ◽  
Sai Chen ◽  
Zhenzhen Tian ◽  
...  
Keyword(s):  
Risk Model ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Support Vector ◽  
Ppi Network ◽  
Hub Genes ◽  
Putative Gene ◽  
Network Analyses ◽  
Cluster 2

Purpose: This study aimed to identify potential diagnostic and therapeutic biomakers for the development ofbreast cancer (BC). Methods: GSE86374 dataset containing 159 samples was acquired from the Gene Expression Omnibus (GEO) database followed by differentially expressed genes (DEGs) identification and cluster analysis. Corresponding functional enrichment and protein-protein interaction (PPI) network analyses were performed to identify hub genes. Prognostic evaluation using clinical information obtained from TCGA database and hub genes was conducted to screen for crucial indicators for BC progression. The risk model was established and validated. Results: In total, 186 DEGs were identified and grouped into four clusters: 96 in cluster 1; 69 in cluster 2; 16 in  cluster 3; and 5 in cluster 4. Functional enrichment analysis showed that DEGs, including ADH1B in cluster 1,  were dramatically enriched in the tyrosine and drug metabolism pathways, while genes in cluster 2, including  SPP1 and RRM2, played crucial roles in PI3K-Akt and p53 signalling pathway. SPP1 and RRM2 served as hub  genes in the PPI network, resulting in an support vector machine classifier with good accuracy and specificity.Ad ditionally, the results of prognostic analysis suggest that age, metastasis stage, SPP1 and ADH1B were correlated with risk of BC, which was validated by using the established risk model analysis. Conclusion: SPP1, RRM2 and ADH1B appear to play vital roles in the development of BC. Age and TNM stage  were also preferentially associated with risk of developing BC. Evaluation of the risk model based on larger sample size and further experimental validation are required.

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