scholarly journals Genetics Responses to Hypoxia and Reoxygenation Stress in Larimichthys crocea Revealed via Transcriptome Analysis and Weighted Gene Co-Expression Network

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3021
Author(s):  
Yibo Zhang ◽  
Jie Ding ◽  
Cheng Liu ◽  
Shengyu Luo ◽  
Xinming Gao ◽  
...  
Keyword(s):  
Gene Network ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Hypoxia Tolerance ◽  
Large Yellow Croaker ◽  
Larimichthys Crocea ◽  
Hub Genes ◽  
Gsk 3Β ◽  
Different Tissues

The large yellow croaker (Larimichthys crocea) is an important marine economic fish in China; however, its intolerance to hypoxia causes widespread mortality. To understand the molecular mechanisms underlying hypoxia tolerance in L. crocea, the transcriptome gene expression profiling of three different tissues (blood, gills, and liver) of L. crocea exposed to hypoxia and reoxygenation stress were performed. In parallel, the gene relationships were investigated based on weighted gene co-expression network analysis (WGCNA). Accordingly, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that several pathways (e.g., energy metabolism, signal transduction, oxygen transport, and osmotic regulation) may be involved in the response of L. crocea to hypoxia and reoxygenation stress. In addition, also, four key modules (darkorange, magenta, saddlebrown, and darkolivegreen) that were highly relevant to the samples were identified by WGCNA. Furthermore, some hub genes within the association module, including RPS16, EDRF1, KCNK5, SNAT2, PFKL, GSK-3β, and PIK3CD, were found. This is the first study to report the co-expression patterns of a gene network after hypoxia stress in marine fish. The results provide new clues for further research on the molecular mechanisms underlying hypoxia tolerance in L. crocea.

scholarly journals Screen Key Genes Associated with Distraction-Induced Osteogenesis of Stem Cells Using Bioinformatics Methods

2021 ◽  
Vol 22 (12) ◽  
pp. 6505
Author(s):  
Jishizhan Chen ◽  
Jia Hua ◽  
Wenhui Song
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Negative Control ◽  
Gene Set Enrichment Analysis ◽  
Venn Diagram ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Two Samples ◽  
Key Genes

Applying mesenchymal stem cells (MSCs), together with the distraction osteogenesis (DO) process, displayed enhanced bone quality and shorter treatment periods. The DO guides the differentiation of MSCs by providing mechanical clues. However, the underlying key genes and pathways are largely unknown. The aim of this study was to screen and identify hub genes involved in distraction-induced osteogenesis of MSCs and potential molecular mechanisms. Material and Methods: The datasets were downloaded from the ArrayExpress database. Three samples of negative control and two samples subjected to 5% cyclic sinusoidal distraction at 0.25 Hz for 6 h were selected for screening differentially expressed genes (DEGs) and then analysed via bioinformatics methods. The Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were investigated. The protein–protein interaction (PPI) network was visualised through the Cytoscape software. Gene set enrichment analysis (GSEA) was conducted to verify the enrichment of a self-defined osteogenic gene sets collection and identify osteogenic hub genes. Results: Three hub genes (IL6, MMP2, and EP300) that were highly associated with distraction-induced osteogenesis of MSCs were identified via the Venn diagram. These hub genes could provide a new understanding of distraction-induced osteogenic differentiation of MSCs and serve as potential gene targets for optimising DO via targeted therapies.

scholarly journals Identification of Key Genes and Pathways Associated with Differences of Subchondral Bone in Osteoarthritis

2020 ◽  
Author(s):  
Yiyuan Zhang ◽  
Rongguo Yu ◽  
Jiayu Zhang ◽  
Eryou Feng ◽  
Haiyang Wang ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Common Chronic Disease ◽  
Drug Candidates ◽  
Therapeutic Modalities ◽  
Pathogenic Genes

Abstract BackgroundOsteoarthritis (OA) is a common chronic disease worldwide. Subchondral bone is an important pathological change in OA and responds more rapidly to adverse loading and events compared to cartilage. However, the pathogenic genes and pathways of subchondral bone are largely unclear.ObjectiveThis study aimed to identify signature differences in genes involved in knee lateral tibial (LT) and medial tibial (MT) plateaus of subchondral bone tissue while exploring their potential molecular mechanisms via bioinformatics analysis.MethodsFirst, the gene expression data of GSE51588 was downloaded from the GEO database. Differentially expressed genes (DEGs) between knee LT and MT were identified, and functional enrichment analyses were performed. Then, a protein-protein interactive network was constructed in order to acquire the hub genes, and modules analysis was conducted using STRING and Cytoscape for further analysis. The enriched hub genes were queried in DGIdb database to find suitable drug candidates in OA.ResultsA total of 202 DEGs (112 upregulated genes and 84 downregulated genes) were determined. In the PPI network, ten hub genes were identified. Five significant modules were identified using the MCODE plugin unit. Functional enrichment analysis revealed the most important signaling pathways. Six of the ten hub genes were targetable by a total of 35 drugs, suggesting their possible therapeutic use for OA .ConclusionsThe identified hub genes and functional enrichment pathways were implicated in the development and progression of subchondral bone in OA, thus improving our understanding of OA and offering molecular targets for future therapeutic modalities.

scholarly journals Integrated Analysis of lncRNAs, mRNAs, and TFs to Identify Regulatory Networks Underlying MAP Infection in Cattle

2021 ◽  
Vol 12 ◽  
Author(s):  
Maryam Heidari ◽  
Abbas Pakdel ◽  
Mohammad Reza Bakhtiarizadeh ◽  
Fariba Dehghanian
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Johne's Disease ◽  
Johne’S Disease ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Complex Nature ◽  
Hub Genes ◽  
Cis And Trans

Johne’s disease is a chronic infection of ruminants that burdens dairy herds with a significant economic loss. The pathogenesis of the disease has not been revealed clearly due to its complex nature. In order to achieve deeper biological insights into molecular mechanisms involved in MAP infection resulting in Johne’s disease, a system biology approach was used. As far as is known, this is the first study that considers lncRNAs, TFs, and mRNAs, simultaneously, to construct an integrated gene regulatory network involved in MAP infection. Weighted gene coexpression network analysis (WGCNA) and functional enrichment analysis were conducted to explore coexpression modules from which nonpreserved modules had altered connectivity patterns. After identification of hub and hub-hub genes as well as TFs and lncRNAs in the nonpreserved modules, integrated networks of lncRNA-mRNA-TF were constructed, and cis and trans targets of lncRNAs were identified. Both cis and trans targets of lncRNAs were found in eight nonpreserved modules. Twenty-one of 47 nonpreserved modules showed significant biological processes related to the immune system and MAP infection. Some of the MAP infection’s related pathways in the most important nonpreserved modules comprise “positive regulation of cytokine-mediated signaling pathway,” “negative regulation of leukocyte migration,” “T-cell differentiation,” “neutrophil activation,” and “defense response.” Furthermore, several genes were identified in these modules, including SLC11A1, MAPK8IP1, HMGCR, IFNGR1, CMPK2, CORO1A, IRF1, LDLR, BOLA-DMB, and BOLA-DMA, which are potentially associated with MAP pathogenesis. This study not only enhanced our knowledge of molecular mechanisms behind MAP infection but also highlighted several promising hub and hub-hub genes involved in macrophage-pathogen interaction.

Identification of Four Key Biomarkers and Small Molecule Drugs Innasopharyngeal Carcinoma by Weighted Gene Co-expression Network Analysis

2020 ◽  
Author(s):  
Xi Pan ◽  
Jian-Hao Liu
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Tumor Stage ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Therapeutic Goals ◽  
Small Molecule Drugs

Abstract Background Nasopharyngeal carcinoma (NPC) is a heterogeneous carcinoma that the underlying molecular mechanisms involved in the tumor initiation, progression, and migration are largely unclear. The purpose of the present study was to identify key biomarkers and small-molecule drugs for NPC screening, diagnosis, and therapy via gene expression profile analysis. Methods Raw microarray data of NPC were retrieved from the Gene Expression Omnibus (GEO) database and analyzed to screen out the potential differentially expressed genes (DEGs). The key modules associated with histology grade and tumor stage was identified by using weighted correlation network analysis (WGCNA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of genes in the key module were performed to identify potential mechanisms. Candidate hub genes were obtained, which based on the criteria of module membership (MM) and high connectivity. Then we used receiver operating characteristic (ROC) curve to evaluate the diagnostic value of hub genes. The Connectivity map database was further used to screen out small-molecule drugs of hub genes. Results A total of 430 DEGs were identified based on two GEO datasets. The green gene module was considered as key module for the tumor stage of NPC via WGCNA analysis. The results of functional enrichment analysis revealed that genes in the green module were enriched in regulation of cell cycle, p53 signaling pathway, cell part morphogenesis. Furthermore, four DEGs-related hub genes in the green module were considered as the final hub genes. Then ROC revealed that the final four hub genes presented with high areas under the curve, suggesting these hub genes may be diagnostic biomarkers for NPC. Meanwhile, we screened out several small-molecule drugs that have provided potentially therapeutic goals for NPC. Conclusions Our research identified four potential prognostic biomarkers and several candidate small-molecule drugs for NPC, which may contribute to the new insights for NPC therapy.

scholarly journals The complexity and robustness of gene network inside the story between miRNAs and splicing isoforms in sacred lotus

2019 ◽  
Author(s):  
Yue Zhang ◽  
Razgar Seyed Rahmani ◽  
Xingyu Yang ◽  
Jinming Chen ◽  
Tao Shi
Keyword(s):  
Gene Network ◽  
Molecular Mechanisms ◽  
Functional Divergence ◽  
Enrichment Analysis ◽  
Flowering Plant ◽  
Transcript Isoforms ◽  
Function Enrichment Analysis ◽  
Splicing Isoforms ◽  
Gene Inhibition ◽  
Mrna Transcriptome

Abstract BACKGROUND. Gene expression is complex and regulated by multiple molecular mechanisms, such as miRNA-mediated gene inhibition and alternative-splicing of pre-mRNAs. However, coordination of interaction between miRNAs with different splicing isoforms, and the role of splicing isoform in response to different cellular environments are largely unexplored in plants. In this study, we analyzed the miRNA and mRNA transcriptome from lotus ( Nelumbo nucifera ), an economically important flowering plant. RESULTS. Through RNA-seq expression analyses among six lotus tissues, the negative regulatory roles of most miRNAs are reflected by their tissue-biased expression and the negative correlation with their targets in expression. Further, the central roles of miRNAs in the gene network was unveiled as there are more frequent interactions between miRNAs and hub isoforms than between miRNAs and non-hub isoforms. Surprisingly, for many genes, their corresponding isoforms were assigned to different co-expressed modules, and they exhibited more divergent mRNA structures including presence and absence of miRNA binding sites, suggesting functional divergence for many isoforms is escalated by both structural and expression divergence. The gene function enrichment analysis of miRNA targeted reveals that miRNAs are involved in regulation of lotus growth and development by regulating plant hormone-related pathway genes. CONCLUSION. Taken together, we carry out a comprehensive and deep analysis between miRNA and mRNA transcriptome to study coordination of interaction between miRNAs with different splicing isoforms. Our study on lotus highlights not only the complicate interactions between the miRNAs and transcript isoforms but also functional divergence of many transcript isoforms from the same locus in plant.

scholarly journals Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses

2020 ◽  
Author(s):  
Basavaraj Vastrad ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti
Keyword(s):  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Go Enrichment ◽  
Jakob Disease

AbstractSporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. Pathway and GO enrichment analyses of DEGs were performed. Furthermore, the protein-protein interaction (PPI) network was predicted using the IntAct Molecular Interaction Database and visualized with Cytoscape software. In addition, hub genes and important modules were selected based on the network. Finally, we constructed target genes - miRNA regulatory network and target genes - TF regulatory network. Hub genes were validated. A total of 891 DEGs 448 of these DEGs presented significant up regulated, and the remaining 443 down regulated were obtained. Pathway enrichment analysis indicated that up regulated genes were mainly linked with glutamine degradation/glutamate biosynthesis, while the down regulated genes were involved in melatonin degradation. GO enrichment analyses indicated that up regulated genes were mainly linked with chemical synaptic transmission, while the down regulated genes were involved in regulation of immune system process. hub and target genes were selected from the PPI network, modules, and target genes - miRNA regulatory network and target genes - TF regulatory network namely YWHAZ, GABARAPL1, EZR, CEBPA, HSPB8, TUBB2A and CDK14. The current study sheds light on the molecular mechanisms of sCJD and may provide molecular targets and diagnostic biomarkers for sCJD.

scholarly journals Exosomal miR-199a-5p Inhibits Tumorigenesis and Angiogenesis by Targeting VEGFA in Osteosarcoma

2021 ◽  
Author(s):  
Lu Zhang ◽  
Hongxin Cao ◽  
Guanghui Gu ◽  
Dehui Hou ◽  
Yunhao You ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Luciferase Reporter ◽  
Pathway Enrichment Analysis ◽  
Osteosarcoma Cell ◽  
Plasma Samples ◽  
Osteosarcoma Cells ◽  
Hub Genes

Abstract Background: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. microRNAs have been found to play a vital role in tumor angiogenesis. Here, we investigated the effects of miR-199a-5p on tumor growth and angiogenesis in osteosarcoma. Furthermore, the underlying molecular mechanisms and signaling pathways were explored.Methods: The datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs (DEmiRNAs) were screened out by the GEO2R online platform. The potential target genes were predicted using the miRTarBase database. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of DEmiRNAs and their target genes was constructed. In addition, the effects of osteosarcoma cell derived exosomal miR-199a-5p on the proliferation, migration and neovascularization of HUVECs were evaluated by conducting EdU assays, Transwell experiments and tube formation assays. A dual-luciferase reporter assay was performed to detect whether VEGFA was the direct target of miR-199a-5p. Furthermore, in vivo xenograft models were established to further investigate the intrinsic role of miR-199a-5p in osteosarcoma tumorigenesis and angiogenesis. Results: A total of 149 DE-miRNAs were screened out, including 136 upregulated miRNAs and 13 downregulated miRNAs in human osteosarcoma plasma samples compared with normal plasma samples. A total of 1313 target genes of the top three upregulated and downregulated miRNAs were predicted. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and VEGFA. By constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-663a, miR-199a-5p and miR-223-3p. In addition, we found that the expression level of miR-199a-5p in exosomes derived from osteosarcoma cells was remarkably higher than the osteosarcoma cells, and the exosomes derived from osteosarcoma cells were transported to HUVECs. Overexpression of miR-199a-5p could significantly inhibited HUVEC proliferation, migration and neovascularization, whereas downregulation of miR-199a-5p expression exerted the opposite effect. Moreover, the in vivo results verified that overexpression of miR-199a-5p in osteosarcoma cells could suppress the growth and angiogenesis of tumors. Conclusion: Our results demonstrated that miR-199a-5p could be transported from osteosarcoma cells to HUVECs through exosomes, subsequently targeting VEGFA and inhibiting the growth and angiogenesis of osteosarcoma. Therefore, miR-199a-5p may act as a biomarker in the diagnosis and treatment of osteosarcoma.

scholarly journals Identification of Potential Key Genes and Molecular Mechanisms of Medulloblastoma Based on Integrated Bioinformatics Approach

2022 ◽  
Vol 2022 ◽  
pp. 1-17
Author(s):  
Md. Rakibul Islam ◽  
Lway Faisal Abdulrazak ◽  
Mohammad Khursheed Alam ◽  
Bikash Kumar Paul ◽  
Kawsar Ahmed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Clinical Information ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
New Treatments

Background. Medulloblastoma (MB) is the most occurring brain cancer that mostly happens in childhood age. This cancer starts in the cerebellum part of the brain. This study is designed to screen novel and significant biomarkers, which may perform as potential prognostic biomarkers and therapeutic targets in MB. Methods. A total of 103 MB-related samples from three gene expression profiles of GSE22139, GSE37418, and GSE86574 were downloaded from the Gene Expression Omnibus (GEO). Applying the limma package, all three datasets were analyzed, and 1065 mutual DEGs were identified including 408 overexpressed and 657 underexpressed with the minimum cut-off criteria of ∣ log   fold   change ∣ > 1 and P < 0.05 . The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways enrichment analyses were executed to discover the internal functions of the mutual DEGs. The outcomes of enrichment analysis showed that the common DEGs were significantly connected with MB progression and development. The Search Tool for Retrieval of Interacting Genes (STRING) database was used to construct the interaction network, and the network was displayed using the Cytoscape tool and applying connectivity and stress value methods of cytoHubba plugin 35 hub genes were identified from the whole network. Results. Four key clusters were identified using the PEWCC 1.0 method. Additionally, the survival analysis of hub genes was brought out based on clinical information of 612 MB patients. This bioinformatics analysis may help to define the pathogenesis and originate new treatments for MB.

scholarly journals Gene Co-expression Network Analysis for Identifying Modules and Functionally Enriched Pathways in Vitiligo Disease: A Systems Biology Study

2020 ◽  
Author(s):  
Afshin Derakhshani ◽  
Homa Mollaei ◽  
Negin Parsamanesh ◽  
Mohammad Fereidouni ◽  
Ebrahim Miri-Moghaddam ◽  
...  
Keyword(s):  
Systems Biology ◽  
Network Analysis ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Neutrophil Migration ◽  
Enrichment Analysis ◽  
Autoimmune Disorder ◽  
Hub Genes ◽  
Novel Biomarkers

Vitiligo is the most common cause of skin, hair, and oral depigmentation which is known as an autoimmune disorder. Genetic and environmental factors have important roles in the progression of the disease. Dysregulation of gene expression, like microRNAs (miRNA), may serve as major relevant factors. Several biological processes are involved in vitiligo disease and developing a comprehensive approach helps us to better understand the molecular mechanisms of disease. In this research, we describe how a weighted gene co-expression network analysis as a systems biology approach assists to define the primary gene modules, hub genes, and messenger RNA (mRNA)-miRNA regulatory network in vitiligo disease as the novel biomarkers. The results demonstrated a module with a high correlation with vitiligo state. Moreover, gene enrichment analysis showed that this module's genes were mostly involved in some biological activities including G protein-coupled receptors signaling pathway, lymphocyte chemotaxis, chemokine activity, neutrophil migration, granulocyte chemotaxis, etc. The co-expression network was constructed using top hub genes of the correlated module which are named as CXCL10, ARL9, AKR1B10, COX7B, RPL26, SPA17, NDUFAF2, RPF2, DAPL1, RPL34, CWC15, NDUFB3, RPL26L1, ACOT13, HSPB11, and NSA2. MicroRNAs prediction tool (miRWalk) revealed top miRNAs correlated with the interested module. Finally, a drug-target network was constructed which indicated interactions of some food and drug administration (FDA) approved drugs with hub genes. Our findings specified one important module and main hub genes which can be considered as novel biomarkers for vitiligo therapeutic purposes.   

scholarly journals Identification of Hub Genes And Potential Molecular Mechanisms In Peripheral Blood Mononuclear Cells of Patients With Parkinson’s Disease

2021 ◽  
Author(s):  
Zhi-Hui Li ◽  
Guang-Tian Wang ◽  
Chun-Ling Chi ◽  
Yu-Nan Zhou ◽  
Dan Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Gene Network ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Hub Genes ◽  
Peripheral Blood Mononuclear ◽  
Hub Gene ◽  
Blood Mononuclear Cells

Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease. The pathogenesis of PD remains elusive, however PD appears to be caused by a complex interaction between environmental and genetic factors affecting various biological processes. The purpose of the present study is to identify hub genes and potential molecular mechanisms in peripheral blood mononuclear cells (PBMCs) of PD patients to aid early diagnosis and start treatment promptly. Two gene expression profiles (GSE22491 and GSE100054) were obtained from the Gene Expression Omnibus (GEO) database, in which 20 PBMC samples from PD patients and 17 controls were included, and the genes were analyzed with GEO2R. 1382 and 512 differentially expressed genes (DEGs) were identified in GSE22491 and GSE100054, respectively. Additionally, a total of 80 significant DEGs were found to co-exist in the two microarray datasets via Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, which showed that the DEGs were mainly enriched in platelet degranulation, blood coagulation, nitric oxide mediated signal transduction, positive regulation of GTPase activity and cellular response to lipopolysaccharide. PPI network, microRNA (miRNA) - hub gene network, and transcription factor (TF)- hub gene network were constructed. In summary, the present study provides data of potential diagnostic biomarkers and therapeutic targets for PD. SRC may be a potential target for the treatment of PD. Additionally, three TFs (HNF4A, CDX2 and FUS), three miRNAs (hsa-miR-16-5p, hsa-miR-103a-3p and hsa-miR-107), may be involved in PD.

Sign in / Sign up

Export Citation Format

Share Document