Identification of Key Candidate Genes and Pathways in Preterm Birth by Integrated Bioinformatical Analysis

Background: Preterm birth（PTB） is a primary cause of neonatal morbidity and mortality, the pathogenic mechanisms of PTB still remain largely unexplored. In the present study, we aimed to identify potential key genes and pathway associated with PTB by bioinformatics analysis. Methods: The GSE46510 dataset was obtained from GEO database. Differentially expressed genes (DEGs) were identified using the limma package in R software, the functional enrichment analysis was performed, and the protein-protein interaction (PPI) network was constructed by Cytoscape software. The network topology was analyzed using MCODE. Results: A total of 335 DEGs were identified from the dataset. The majority of up-regulated DEGs were significantly enriched in inflammatory response, while down-regulated DEGs were mainly enriched in mitotic nuclear division. The top 5 hub up regulated genes were ITGAM, IL1B, ITGAX, NFKB1, and SOCS3. Pathway analysis indicated enrichment in Cytokine-cytokine receptor interaction, signaling by Interleukins. The top 5 hub down regulated genes were CXCR4, ANAPC10, ANAPC4, UBE2V2, UBA3, Pathway analysis indicated enrichment in Ubiquitin mediated proteolysis, Phosphorylation of the APC/C. Conclusion: Our study indicated genes and pathways in PTB by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of PTB.

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The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

BioMed Research International ◽

10.1155/2020/4980609 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Shuqiang Li ◽

Huijie Shao ◽

Liansheng Chang

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Receptor Interaction ◽

Ppi Network ◽

Hub Genes ◽

R Language ◽

Protein Protein Interaction

Epilepsy is most common in patients with tuberous sclerosis complex (TSC). However, in addition to the challenging treatment, the pathogenesis of epilepsy is still controversial. To determine the transcriptome characteristics of perituberal tissue (PT) and clarify its role in the pathogenesis of epilepsy, GSE16969 was downloaded from the GEO database for further study by comprehensive bioinformatics analysis. Identification of differentially expressed genes (DEGs), functional enrichment analysis, construction of protein-protein interaction (PPI) network, and selection of Hub genes were performed using R language, Metascape, STRING, and Cytoscape, respectively. Comparing with cortical tuber (CT), 220 DEGs, including 95 upregulated and 125 downregulated genes, were identified in PT and mainly enriched in collagen-containing extracellular matrix and positive regulation of receptor-mediated endocytosis, as well as the pathways of ECM-receptor interaction and neuroactive ligand-receptor interaction. As for normal cortex (NC), 1549 DEGs, including 30 upregulated and 1519 downregulated genes, were identified and mainly enriched in presynapse, dendrite and axon, and also the pathways of dopaminergic synapse and oxytocin signaling pathway. In the PPI network, 4 hub modules were found between PT and CT, and top 5 hub modules were selected between PT and NC. C3, APLNR, ANXA2, CD44, CLU, CP, MCHR2, HTR1E, CTSG, APP, and GNG2 were identified as Hub genes, of which, C3, CD44, ANXA2, HTR1E, and APP were identified as Hub-BottleNeck genes. In conclusion, PT has the unique characteristics different from CT and NC in transcriptome and makes us further understand its importance in the TSC-associated epilepsy.

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Application of Bioinformatics Methods to Identify Key Genes and Functions in Chronic Pelvic Pain

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/7257405 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Wenchao Sun ◽

Qiji Ju

Keyword(s):

Pelvic Pain ◽

Chronic Pelvic Pain ◽

Single Gene ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Gene Expression Omnibus ◽

Functional Enrichment ◽

Receptor Interaction ◽

Protein Protein Interaction ◽

Key Genes

Neuropathologic pain (NPP) occurs in most patients with chronic pelvic pain (CPP), and the unique physiological characteristics of visceral sensory neurons make the current analgesic effect of CPP patients not optimistic. Therefore, this study explored the possible biological characteristics of key genes in CPP through the bioinformatics method. CPP-related dataset GSE131619 was downloaded from Gene Expression Omnibus to investigate the differentially expressed genes (DEGs) between lumbar dorsal root ganglia (DRG) and sacral DRG, and the functional enrichment analysis was performed. A protein-protein interaction (PPI) network was constructed to search subnet modules of specific biological processes, and then, the genes in the subnet were enriched by single gene set analysis. A CPP mouse model was established, and the expression of key genes were identified by qPCR. The results showed that 127 upregulated DEGs and 103 downregulated DEGs are identified. Functional enrichment analysis showed that most of the genes involved in signal transduction were involved in the pathway of receptor interaction. A subnet module related to neural signal regulation was identified in PPI, including CHRNB4, CHRNA3, and CHRNB2. All three genes were associated with neurological or inflammatory activity and are downregulated in the sacral spinal cord of CPP mice. This study provided three key candidate genes for CPP: CHRNB4, CHRNA3, and CHRNB2, which may be involved in the occurrence and development of CPP, and provided a powerful molecular target for the clinical diagnosis and treatment of CPP.

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

Animals ◽

10.3390/ani11020295 ◽

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.

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The Role of Circular RNA CDR1as/ciRS-7 in Regulating Tumor Microenvironment: A Pan-Cancer Analysis

Biomolecules ◽

10.3390/biom9090429 ◽

2019 ◽

Vol 9 (9) ◽

pp. 429 ◽

Cited By ~ 24

Author(s):

Zou ◽

Zheng ◽

Deng ◽

Yang ◽

Xie ◽

...

Keyword(s):

Tumor Microenvironment ◽

Signaling Pathway ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Circular Rna ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Receptor Interaction

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.

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Comparative Transcriptome Analysis Suggests Key Roles for 5-Hydroxytryptamlne Receptors in Control of Goose Egg Production

Genes ◽

10.3390/genes11040455 ◽

2020 ◽

Vol 11 (4) ◽

pp. 455 ◽

Cited By ~ 1

Author(s):

Qingyuan Ouyang ◽

Shenqiang Hu ◽

Guosong Wang ◽

Jiwei Hu ◽

Jiaman Zhang ◽

...

Keyword(s):

Egg Production ◽

Expression Profiles ◽

Expression Patterns ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Production Performance ◽

Functional Enrichment ◽

Differentially Expressed ◽

Receptor Interaction ◽

Anser Anser

To date, research on poultry egg production performance has only been conducted within inter or intra-breed groups, while those combining both inter- and intra-breed groups are lacking. Egg production performance is known to differ markedly between Sichuan white goose (Anser cygnoides) and Landes goose (Anser anser). In order to understand the mechanism of egg production performance in geese, we undertook this study. Here, 18 ovarian stromal samples from both Sichuan white goose and Landes goose at the age of 145 days (3 individuals before egg production initiation for each breed) and 730 days (3 high- and low egg production individuals during non-laying periods for each breed) were collected to reveal the genome-wide expression profiles of ovarian mRNAs and lncRNAs between these two geese breeds at different physiological stages. Briefly, 58, 347, 797, 777, and 881 differentially expressed genes (DEGs) and 56, 24, 154, 105, and 224 differentially expressed long non-coding RNAs (DElncRNAs) were found in LLD vs. HLD (low egg production Landes goose vs. high egg production Landes goose), LSC vs. HSC (low egg production Sichuan White goose vs. high egg production Sichuan white goose), YLD vs. YSC (young Landes goose vs. young Sichuan white goose), HLD vs. HSC (high egg production Landes goose vs. high egg production Sichuan white goose), and LLD vs. LSC (low egg production Landes goose vs. low egg production Sichuan white goose) groups, respectively. Functional enrichment analysis of these DEGs and DElncRNAs suggest that the “neuroactive ligand–receptor interaction pathway” is crucial for egg production, and particularly, members of the 5-hydroxytryptamine receptor (HTR) family affect egg production by regulating ovarian metabolic function. Furthermore, the big differences in the secondary structures among HTR1F and HTR1B, HTR2B, and HTR7 may lead to their different expression patterns in goose ovaries of both inter- and intra-breed groups. These results provide novel insights into the mechanisms regulating poultry egg production performance.

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Comparative transcriptomic analysis of porcine peripheral blood reveals differentially expressed genes from the cytokine–cytokine receptor interaction pathway related to health status

Genome ◽

10.1139/gen-2017-0074 ◽

2017 ◽

Vol 60 (12) ◽

pp. 1021-1028 ◽

Cited By ~ 2

Author(s):

M.H. Ye ◽

H. Bao ◽

Y. Meng ◽

L.L. Guan ◽

P. Stothard ◽

...

Keyword(s):

Health Status ◽

Differentially Expressed Genes ◽

Peripheral Blood ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Cytokine Receptor ◽

Functional Enrichment ◽

Differentially Expressed ◽

Receptor Interaction ◽

Marker Genes

While some research has looked into the host genetic response in pigs challenged with specific viruses or bacteria, few studies have explored the expression changes of transcripts in the peripheral blood of sick pigs that may be infected with multiple pathogens on farms. In this study, the architecture of the peripheral blood transcriptome of 64 Duroc sired commercial pigs, including 18 healthy animals at entry to a growing facility (set as a control) and 23 pairs of samples from healthy and sick pen mates, was generated using RNA-Seq technology. In total, 246 differentially expressed genes were identified to be specific to the sick animals. Functional enrichment analysis for those genes revealed that the over-represented gene ontology terms for the biological processes category were exclusively immune activity related. The cytokine–cytokine receptor interaction pathway was significantly enriched. Nine functional genes from this pathway encoding members (as well as their receptors) of the interleukins, chemokines, tumor necrosis factors, colony stimulating factors, activins, and interferons exhibited significant transcriptional alteration in sick animals. Our results suggest a subset of novel marker genes that may be useful candidate genes in the evaluation and prediction of health status in pigs under commercial production conditions.

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Identification of Latent Diagnostic Biomarkers and Biological Pathways in Dermatomyositis Based on WGCNA

Journal of Oncology ◽

10.1155/2021/1920111 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Shaxi Ouyang ◽

Yifang Liu ◽

Changjuan Xiao ◽

Qinghua Zeng ◽

Xun Luo ◽

...

Keyword(s):

Cell Lines ◽

Differentially Expressed Gene ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Receptor Interaction ◽

Interferon Α ◽

Pathway Enrichment Analysis ◽

Oligoadenylate Synthetase

Introduction. Dermatomyositis (DM) is a chronic autoimmune disease of predominantly lymphocytic infiltration mainly involving the transverse muscle. Its pathogenesis is remaining unknown. This research is designed to probe the latent pathogenesis of dermatomyositis, identify potential biomarkers, and reveal the pathogenesis of dermatomyositis through information biology analysis of gene chips. Methods. In this study, we utilised the GSE14287 and GSE11971 datasets rooted in the Gene Expression Omnibus (GEO) databank, which included a total of 62 DM samples and 9 normal samples. The datasets were combined, and the differentially expressed gene sets were subjected to weighted gene coexpression network analysis, and the hub gene was screened using a protein interaction network from genes in modules highly correlated with dermatomyositis progression. Results. A total of 3 key genes—myxovirus resistance-2 (MX2), oligoadenylate synthetase 1 (OAS1), and oligoadenylate synthetase 2 (OAS2)—were identified in combination with cell line samples, and the expressions of the 3 genes were verified separately. The results showed that MX2, OAS1, and OAS2 were highly expressed in LPS-treated cell lines compared to normal cell lines. The results of pathway enrichment analysis of the genes indicated that all 3 genes were enriched in the cytosolic DNA signalling and cytokine and cytokine receptor interaction signalling pathways; the results of functional enrichment analysis showed that all 3 were enriched in interferon-α response and interferon-γ response functions. Conclusions. This is important for the study of the pathogenesis and objective treatment of dermatomyositis and provides important reference information for the targeted therapy of dermatomyositis.

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

10.7287/peerj.preprints.27586v1 ◽

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.

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Apolipoprotein B Is Associated With the Microenvironment of Cholangiocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.654689 ◽

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.

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