Identification, Functional Analysis and Preliminary Validation of Differentially Expressed Genes in Hyperacute Cerebral Infarction Patients

Abstract Background/AimsAt present, most studies on ischemic stroke and micro RNA are focused on 24h after stroke. Therefore, our experiment intends to analyze the differentially expressed genes in hyperacute cerebral infarction patients, and to analyze the relationship between the most significantly differentially expressed miRNA and clinical characteristics. MethodsDownload miRNA expression microarray and gene expression microarray from GEO database, screen differentially expressed genes and miRNA by bioinformatics method, and analyze their biological functions. The peripheral plasma of patients with hyperacute stroke was collected, the related miRNAs were extracted, and the relationship between them and clinical characteristics was analyzed. ResultsThe microarray included 39 hyperacute cerebral infarction patients patients and 33 healthy volunteers and 5 differentially expressed miRNAs and 1107 differentially expressed genes were obtained by analysis. MiR-3156-5p was selected to further analyze and verify the correlation with the clinical characteristics of patients. The results showed that the expression level of miR-3156-5p was significantly positively correlated with triglyceride level, and had a significant negative impact on stroke. The low level of miR-3156-5p in hyperacute cerebral infarction patients may be one of the initiating factors of neuroinflammation induced by ischemic stroke, and functional analysis and some existing experimental results also support this view. ConclusionsIn our study, a series of differentially expressed genes and differentially expressed miRNAs were screened by analyzing GEO data sets. In addition, the low expression of miR-3156-5p in hyperacute cerebral infarction patients may be one of the initiating factors of neuroinflammation induced by ischemic stroke.

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Abstract TP166: Age-Associated Transcriptomic Alterations in Patients With Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp166 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Gina Sykes ◽

Yusra Batool ◽

Joseph Kamtchum Tatuene ◽

Sarah Zehnder ◽

Glen C Jickling

Keyword(s):

Gene Expression ◽

Functional Analysis ◽

Ischemic Stroke ◽

Immune System ◽

B Cell ◽

Differentially Expressed Genes ◽

Hemorrhagic Transformation ◽

Differentially Expressed ◽

P Value ◽

Humoral Immune

Introduction: Immune system dysregulation occurs with age. This includes an increase in inflammation, and immunosenescence, the inability to efficiently respond to new immune challenges. These changes are evident in various diseases but have yet to be evaluated in a population with ischemic stroke. Age is an important factor in stroke, contributing to stroke risk, outcome and risk of hemorrhagic transformation. This study aimed to assess the changes that occur with age in the leukocyte gene expression of patients with ischemic stroke. Methods: Two cohorts of acute ischemic stroke patients were analyzed; cohort 1 (n=94) and cohort 2 (n=79). RNA was isolated from PAXgene tubes and processed on Affymetrix microarrays. Differentially expressed genes associated with age quartiles were identified by ANCOVA, adjusted for sex and batch. Functional analysis identified age-associated pathways. Differentially expressed genes were compared with previous non-stroke aging studies in whole blood. Results: There were 61 and 442 age-associated genes in cohorts 1 and 2 respectively (FDR-corrected p<0.05, partial correlation coefficient ≥ |0.3|). Nineteen genes, including CR2, CCR6 and CXCR5 , were found in common and decreased with age among both cohorts (max-log10(p value) = 17). Functional analysis of the 61 and 442 genes revealed with advancing age there is a change in the humoral immune system, including antibody production and B cell proliferation. When compared to aging gene expression studies in controls, 52% of age-associated genes in cohort 1 and 31% of cohort 2 age-associated genes overlapped with those found in controls, and 16 of the 19 common genes to both cohorts overlapped in controls (max-log10(p value) = 15). Conclusion: In patients with acute stroke there is a change in leukocyte gene expression with advancing age. Changes included a shift in humoral immune response with a potentially impaired B cell response. While many of the age-associated alterations in gene expression present in stroke are similar to non-stroke controls, these changes warrant further investigation for their impact on stroke outcome and risk.

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Comparative functional genomic analysis of Alzheimer’s affected and naturally aging brains

PeerJ ◽

10.7717/peerj.8682 ◽

2020 ◽

Vol 8 ◽

pp. e8682

Author(s):

Yi-Shian Peng ◽

Chia-Wei Tang ◽

Yi-Yun Peng ◽

Hung Chang ◽

Chien-Lung Chen ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Microarray Data ◽

Gene List ◽

Amyloid Β ◽

Differentially Expressed ◽

Gene Expression Microarray ◽

Expression Microarray ◽

Functional Genomic Analysis ◽

Gene Expression Microarray Data

Background Alzheimer’s disease (AD) is a prevalent progressive neurodegenerative human disease whose cause remains unclear. Numerous initially highly hopeful anti-AD drugs based on the amyloid-β (Aβ) hypothesis of AD have failed recent late-phase tests. Natural aging (AG) is a high-risk factor for AD. Here, we aim to gain insights in AD that may lead to its novel therapeutic treatment through conducting meta-analyses of gene expression microarray data from AG and AD-affected brain. Methods Five sets of gene expression microarray data from different regions of AD (hereafter, ALZ when referring to data)-affected brain, and one set from AG, were analyzed by means of the application of the methods of differentially expressed genes and differentially co-expressed gene pairs for the identification of putatively disrupted biological pathways and associated abnormal molecular contents. Results Brain-region specificity among ALZ cases and AG-ALZ differences in gene expression and in KEGG pathway disruption were identified. Strong heterogeneity in AD signatures among the five brain regions was observed: HC/PC/SFG showed clear and pronounced AD signatures, MTG moderately so, and EC showed essentially none. There were stark differences between ALZ and AG. OXPHOS and Proteasome were the most disrupted pathways in HC/PC/SFG, while AG showed no OXPHOS disruption and relatively weak Proteasome disruption in AG. Metabolic related pathways including TCA cycle and Pyruvate metabolism were disrupted in ALZ but not in AG. Three pathogenic infection related pathways were disrupted in ALZ. Many cancer and signaling related pathways were shown to be disrupted AG but far less so in ALZ, and not at all in HC. We identified 54 “ALZ-only” differentially expressed genes, all down-regulated and which, when used to augment the gene list of the KEGG AD pathway, made it significantly more AD-specific.

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Comprehensive Analysis of Differentially Expressed Genes and Key Pathways in Neuropathic Pain by Spinal Nerve Ligation

10.21203/rs.3.rs-74125/v1 ◽

2020 ◽

Author(s):

Chao Xu ◽

HuiFang Li ◽

YunPeng Zhang ◽

TianYu Liu ◽

Yi Feng

Keyword(s):

Functional Analysis ◽

Neuropathic Pain ◽

Differentially Expressed Genes ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Spinal Nerve ◽

Spinal Nerve Ligation ◽

Differentially Expressed ◽

Hub Genes ◽

Long Term Treatment

Abstract Background: Neuropathic pain can cause significant physical and economic burden to people, and there are no effective long-term treatment methods for this condition. We conducted a bioinformatics analysis of microarray data to identify related mechanisms to determine strategies for more effective treatments of neuropathic pain.Methods: GSE24982 and GSE63442 microarray datasets were extracted from the Gene Expression Omnibus (GEO) database to analyze transcriptome differences of neuropathic pain in the dorsal root ganglions caused by spinal nerve ligation. We filtered the differentially expressed genes (DEGs) in the two datasets and Webgestalt was applied to conduct GeneOntology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the shared DEGs. String Database and Cytoscape software were used to construct the Protein-Protein Interaction (PPI) network to determine the hub genes, which were subsequently verified in the GSE30691 dataset. Finally, miRDB and miRWalk Databases were used to predict potential miRNA of the selected DEGs.Results: A total of 182 overlapped DEGs were found between GSE24982 and GSE63442 datasets. The GO functional analysis and KEGG enrichment analysis showed that the selected DEGs were mainly enriched in infection, transmembrane transport of ion channels, and synaptic transmission. Combining the results of PPI analysis and the verification of the GSE30691 dataset, we identified seven hub genes related to neuropathic pain (Atf3, Aif1, Ctss, Gfap, Scg2, Jun, and Vgf). Predicted miRNA targeting each selected hub genes were identified.Conclusion: Seven hub genes related to the pathogenesis of neuropathic pain and potential targeting miRNA were identified, expanding understanding of the mechanism of neuropathic pain and facilitating treatment development.

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Transcriptome analysis of miRNA and mRNA in the livers of pigs with highly diverged backfat thickness

Scientific Reports ◽

10.1038/s41598-019-53377-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Kai Xing ◽

Xitong Zhao ◽

Hong Ao ◽

Shaokang Chen ◽

Ting Yang ◽

...

Keyword(s):

Fatty Acid ◽

Energy Metabolism ◽

Differentially Expressed Genes ◽

Regulatory Network ◽

Acid Synthesis ◽

Fat Deposition ◽

Differentially Expressed ◽

Backfat Thickness ◽

Lipid Deposition ◽

Differentially Expressed Mirnas

AbstractFat deposition is very important in pig production, and its mechanism is not clearly understood. MicroRNAs (miRNAs) play critical roles in fat deposition and energy metabolism. In the current study, we investigated the mRNA and miRNA transcriptome in the livers of Landrace pigs with extreme backfat thickness to explore miRNA-mRNA regulatory networks related to lipid deposition and metabolism. A comparative analysis of liver mRNA and miRNA transcriptomes from pigs (four pigs per group) with extreme backfat thickness was performed. We identified differentially expressed genes from RNA-seq data using a Cufflinks pipeline. Seventy-one differentially expressed genes (DEGs), including twenty-eight well annotated on the porcine reference genome genes, were found. The upregulation genes in pigs with higher backfat thickness were mainly involved in fatty acid synthesis, and included fatty acid synthase (FASN), glucokinase (GCK), phosphoglycerate dehydrogenase (PHGDH), and apolipoprotein A4 (APOA4). Cytochrome P450, family 2, subfamily J, polypeptide 34 (CYP2J34) was lower expressed in pigs with high backfat thickness, and is involved in the oxidation of arachidonic acid. Moreover, 13 differentially expressed miRNAs were identified. Seven miRNAs were associated with fatty acid synthesis, lipid metabolism, and adipogenic differentiation. Based on comprehensive analysis of the transcriptome of both mRNAs and miRNAs, an important regulatory network, in which six DEGs could be regulated by differentially expressed miRNAs, was established for fat deposition. The negative correlate in the regulatory network including, miR-545-5p and GRAMD3, miR-338 and FASN, and miR-127, miR-146b, miR-34c, miR-144 and THBS1 indicate that direct suppressive regulation may be involved in lipid deposition and energy metabolism. Based on liver mRNA and miRNA transcriptomes from pigs with extreme backfat thickness, we identified 28 differentially expressed genes and 13 differentially expressed miRNAs, and established an important miRNA-mRNA regulatory network. This study provides new insights into the molecular mechanisms that determine fat deposition in pigs.

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Identification of differentially expressed genes induced by transient ischemic stroke

Molecular Brain Research ◽

10.1016/s0169-328x(02)00135-3 ◽

2002 ◽

Vol 101 (1-2) ◽

pp. 12-22 ◽

Cited By ~ 42

Author(s):

David A Schwarz ◽

Guy Barry ◽

Kenneth B Mackay ◽

Frank Manu ◽

Gregory S Naeve ◽

...

Keyword(s):

Ischemic Stroke ◽

Differentially Expressed Genes ◽

Differentially Expressed

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A Differential Host Response to Viral Infection Defines a Subset of Earlier-Onset Diverticulitis Patients

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.273.sch ◽

2018 ◽

Vol 27 (3) ◽

pp. 249-255 ◽

Cited By ~ 1

Author(s):

Kathleen M Schieffer ◽

Bryan P Kline ◽

Leonard R Harris ◽

Sue Deiling ◽

Walter A Koltun ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Principal Component ◽

Differentially Expressed ◽

Rna Seq ◽

Viral Pathogen ◽

Viral Response ◽

Elevated Expression ◽

Bioinformatic Approaches ◽

Relationship Of ◽

The Relationship

Background & Aims: Diverticulitis is the chronic inflammation of diverticula. Whether the pathophysiology of earlier-onset patients differs from later-onset patients is unknown. We profiled the colonic transcriptomes of these two patient populations to gain insight into the molecular underpinnings of diverticulitis. Methods: We conducted deep RNA sequencing (RNA-seq) on colonic segments surgically resected from earlier-onset (<42 years old, n=13) and later-onset (>65 years old, n=13) diverticulitis patients. We used bioinformatic approaches to cluster the patients based on the relationship of differentially expressed genes and to inform on the molecular pathways that segregated the clusters. Results: Principal component analysis identified three patient clusters; diverticulitis later-onset (DVT-LO), diverticulitis mixed-onset (DVT-MO), and diverticulitis earlier-onset (DVT-EO). The patients comprising DVT-EO, which was the majority of earlier-onset patients, displayed increased expression of anti-viral response genes. This finding was confirmed using an independent weighted co-expression network analysis (WGCNA) of differentially expressed genes. Conclusions: We found that the majority of patients with earlier-onset disease contained elevated expression of host genes involved in the anti-viral response. Thus, susceptibility to a viral pathogen may offer one explanation why some individuals develop diverticulitis at an earlier age.

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