scholarly journals Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yujie Zhu ◽  
Yuxin Lin ◽  
Wenying Yan ◽  
Zhandong Sun ◽  
Zhi Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Coronary Syndrome ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Pathway Enrichment ◽  
Coronary Syndrome ◽  
Life Threatening

Acute coronary syndrome (ACS) is a life-threatening disease that affects more than half a million people in United States. We currently lack molecular biomarkers to distinguish the unstable angina (UA) and acute myocardial infarction (AMI), which are the two subtypes of ACS. MicroRNAs play significant roles in biological processes and serve as good candidates for biomarkers. In this work, we collected microRNA datasets from the Gene Expression Omnibus database and identified specific microRNAs in different subtypes and universal microRNAs in all subtypes based on our novel network-based bioinformatics approach. These microRNAs were studied for ACS association by pathway enrichment analysis of their target genes. AMI and UA were associated with 27 and 26 microRNAs, respectively, nine of them were detected for both AMI and UA, and five from each subtype had been reported previously. The remaining 22 and 21 microRNAs are novel microRNA biomarkers for AMI and UA, respectively. The findings are then supported by pathway enrichment analysis of the targets of these microRNAs. These novel microRNAs deserve further validation and will be helpful for personalized ACS diagnosis.

scholarly journals SARS-CoV-2 Infections - Gene Expression Omnibus (GEO) Data Mining, Pathway Enrichment Analysis, and Prediction of Repurposable Drugs/Compounds

2020 ◽  
Author(s):  
Srilakshmi Chaparala ◽  
Carrie L Iwema ◽  
Ansuman Chattopadhyay
Keyword(s):  
Gene Expression ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Host Cells ◽  
In Vivo Studies ◽  
Pathway Enrichment Analysis ◽  
Gene Expressions ◽  
Pathway Enrichment

The COVID-19 global pandemic has created dire consequences with an alarming rate of morbidity and mortality. There are not yet vaccine or efficacious treatment options to combat the causative SARS-CoV-2 infection. This paper describes the identification of potentially repurposable drugs for COVID-19 treatment by conducting pathway enrichment analysis on publicly available Gene Expression Omnibus datasets. We first determined SARS-CoV-2 infection-induced alterations of host gene expressions and pathways. We then identified drugs or compounds that target and counter virus-triggered cellular perturbations, suggesting their potential repurposing for COVID-19 treatment. The key findings are that SARS-CoV-2 infection in host cells induces mitochondrial dysfunction, inhibits oxidative phosphorylation, and activates several immune response and pro-inflammatory pathways. Triptolide, the major bioactive component of a traditional Chinese medicine herb, may rescue mitochondrial dysfunction by activating oxidative phosphorylation. Further in vitro and in vivo studies are necessary to verify these results prior to clinical application.

scholarly journals Network Pharmacology-Based Study on the Mechanism of Gegen Qinlian Decoction against Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Qiaowei Fan ◽  
Lin Guo ◽  
Jingming Guan ◽  
Jing Chen ◽  
Yujing Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Target Genes ◽  
Enrichment Analysis ◽  
R Package ◽  
Gastrointestinal Diseases ◽  
Gene Expression Omnibus ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ppi Network

Purpose. Gegen Qinlian decoction (GQD) has been used to treat gastrointestinal diseases, such as diarrhea and ulcerative colitis (UC). A recent study demonstrated that GQD enhanced the effect of PD-1 blockade in colorectal cancer (CRC). This study used network pharmacology analysis to investigate the mechanisms of GQD as a potential therapeutic approach against CRC. Materials and Methods. Bioactive chemical ingredients (BCIs) of GQD were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CRC-specific genes were obtained using the gene expression profile GSE110224 from the Gene Expression Omnibus (GEO) database. Target genes related to BCIs of GQD were then screened out. The GQD-CRC ingredient-target pharmacology network was constructed and visualized using Cytoscape software. A protein-protein interaction (PPI) network was subsequently constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of clusterProfiler. Results. One hundred and eighteen BCIs were determined to be effective on CRC, including quercetin, wogonin, and baicalein. Twenty corresponding target genes were screened out including PTGS2, CCNB1, and SPP1. Among these genes, CCNB1 and SPP1 were identified as crucial to the PPI network. A total of 212 GO terms and 6 KEGG pathways were enriched for target genes. Functional analysis indicated that these targets were closely related to pathophysiological processes and pathways such as biosynthetic and metabolic processes of prostaglandins and prostanoids, cytokine and chemokine activities, and the IL-17, TNF, Toll-like receptor, and nuclear factor-kappa B (NF-κB) signaling pathways. Conclusion. The study elucidated the “multiingredient, multitarget, and multipathway” mechanisms of GQD against CRC from a systemic perspective, indicating GQD to be a candidate therapy for CRC treatment.

scholarly journals Prognostic values and prospective pathway signaling of MicroRNA-182 in ovarian cancer: a study based on gene expression omnibus (GEO) and bioinformatics analysis

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yaowei Li ◽  
Li Li
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Gynecological Cancer ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction

Abstract Background Ovarian carcinoma (OC) is a common cause of death among women with gynecological cancer. MicroRNAs (miRNAs) are believed to have vital roles in tumorigenesis of OC. Although miRNAs are broadly recognized in OC, the role of has-miR-182-5p (miR-182) in OC is still not fully elucidated. Methods We evaluated the significance of miR-182 expression in OC by using analysis of a public dataset from the Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we downloaded three mRNA datasets of OC and normal ovarian tissues (NOTs), GSE14407, GSE18520 and GSE36668, from GEO to identify differentially expressed genes (DEGs). Then the targeted genes of hsa-miR-182-5p (TG_miRNA-182-5p) were predicted using miRWALK3.0. Subsequently, we analyzed the gene overlaps integrated between DEGs in OC and predicted target genes of miR-182 by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and the prognostic effects of the hub genes were analyzed. Results A common pattern of up-regulation for miR-182 in OC was found in our review of the literature. A total of 268 DEGs, both OC-related and miR-182-related, were identified, of which 133 genes were discovered from the PPI network. A number of DEGs were enriched in extracellular matrix organization, pathways in cancer, focal adhesion, and ECM-receptor interaction. Two hub genes, MCM3 and GINS2, were significantly associated with worse overall survival of patients with OC. Furthermore, we identified covert miR-182-related genes that might participate in OC by network analysis, such as DCN, AKT3, and TIMP2. The expressions of these genes were all down-regulated and negatively correlated with miR-182 in OC. Conclusions Our study suggests that miR-182 is essential for the biological progression of OC.

A Method of Pathway Enrichment Analysis Based Gene Expression Variability

2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Expression Variability ◽  
Pathway Enrichment

scholarly journals Comparative pathway enrichment analysis in gastrointestinal cell lines Caco-2, HT-29, HEPG2, and colon fibroblasts using a custom expression panel for tight-junction and cytoskeletal regulatory genes

2019 ◽  
Author(s):  
JM Robinson
Keyword(s):  
Gene Expression ◽  
Comparative Analysis ◽  
Tight Junction ◽  
Cell Lines ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Intestinal Epithelial ◽  
Expression Data ◽  
Pathway Enrichment ◽  
Ht 29

AbstractThis brief report details results from a comparative analysis of Nanostring expression data between cell lines HEPG2, Caco-2, HT-29, and colon fibroblasts. Raw and normalized data are available publicly in the NCBI GEO/Bioproject databases. Results identify cell-line specific variations in gene expression relevant to intestinal epithelial function.

scholarly journals Identification of Key miRNAs in the Treatment of Dabrafenib-Resistant Melanoma

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guangyu Gao ◽  
Zhen Yao ◽  
Jiaofeng Shen ◽  
Yulong Liu
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Obvious Association

Dabrafenib resistance is a significant problem in melanoma, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism of drug resistance of dabrafenib and to explore the key genes and pathways that mediate drug resistance in melanoma. GSE117666 was downloaded from the Gene Expression Omnibus (GEO) database and 492 melanoma statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Besides, differentially expressed miRNAs (DEMs) were identified by taking advantage of the R software and GEO2R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and FunRich was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to identify potential pathways and functional annotations linked with melanoma chemoresistance. 9 DEMs and 872 mRNAs were selected after filtering. Then, target genes were uploaded to Metascape to construct protein-protein interaction (PPI) network. Also, 6 hub mRNAs were screened after performing the PPI network. Furthermore, a total of 4 out of 9 miRNAs had an obvious association with the survival rate ( P < 0.05 ) and showed a good power of risk prediction model of over survival. The present research may provide a deeper understanding of regulatory genes of dabrafenib resistance in melanoma.

scholarly journals Systems Pharmacological Approach to Investigate the Mechanism of Acori Tatarinowii Rhizoma for Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Zhenyan Song ◽  
Fang Yin ◽  
Biao Xiang ◽  
Bin Lan ◽  
Shaowu Cheng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Biological Processes ◽  
Pathway Enrichment ◽  
Study Results ◽  
Target Network ◽  
Anti Inflammatory

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer’s disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer’s disease.

Identification of differential gene expression related to epirubicin-induced cardiomyopathy in breast cancer patients

2019 ◽  
Vol 39 (4) ◽  
pp. 393-401 ◽  
Author(s):  
J Peng ◽  
Z Wang ◽  
Y Li ◽  
D Lv ◽  
X Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Enrichment Analysis ◽  
Global Gene Expression ◽  
Pathway Enrichment Analysis ◽  
Breast Cancer Patients ◽  
Chlorophyll Metabolism ◽  
Pathway Enrichment ◽  
Before And After

Background: Epirubicin is a potent chemotherapeutic agent for the treatment of breast cancer. However, it may lead to cardiotoxicity and cardiomyopathy, and no reliable biomarker was available for the early prediction of epirubicin-induced cardiomyopathy. Methods: Global gene expression changes of peripheral blood cells were studied using high-throughput RNA sequencing in three pair-matched breast cancer patients (patients who developed symptomatic cardiomyopathy paired with patients who did not) before and after the full session of epirubicin-based chemotherapy. Functional analysis was conducted using gene ontology and pathway enrichment analysis. Results: We identified 13 significantly differentially expressed genes between patients who developed symptomatic epirubicin-induced cardiomyopathy and their paired control who did not. Among them, the upregulated Bcl-associated X protein was related to “apoptosis,” while the downregulated 5′-aminolevulinate synthase 2 (ALAS2) was related to both “glycine, serine, and threonine metabolism” and “porphyrin and chlorophyll metabolism” in pathway enrichment analysis. Conclusions: ALAS2 and the metabolic pathways which were involved may play an important role in the development of epirubicin-induced cardiomyopathy. ALAS2 may be useful as an early biomarker for epirubicin-induced cardiotoxicity detection.

scholarly journals Host–Viral Interactions Revealed among Shared Transcriptomics Signatures of ARDS and Thrombosis: A Clue into COVID-19 Pathogenesis

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e403-e412
Author(s):  
Aastha Mishra ◽  
Shankar Chanchal ◽  
Mohammad Z. Ashraf
Keyword(s):  
Gene Expression ◽  
Virus Disease ◽  
Meta Analysis ◽  
Random Effect ◽  
Enrichment Analysis ◽  
Coagulation Factors ◽  
Gene Expression Omnibus ◽  
Endothelial Damage ◽  
Pathway Enrichment Analysis ◽  
Hub Genes

AbstractSevere novel corona virus disease 2019 (COVID-19) infection is associated with a considerable activation of coagulation pathways, endothelial damage, and subsequent thrombotic microvascular injuries. These consistent observations may have serious implications for the treatment and management of this highly pathogenic disease. As a consequence, the anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of two independently publicly available datasets of ARDS and venous thromboembolism (VTE). Datasets GSE76293 and GSE19151 derived from National Centre for Biotechnology Information–Gene Expression Omnibus (NCBI-GEO) database were used for ARDS and VTE, respectively. Integrative meta-analysis of expression data (INMEX) tool preprocessed the datasets and effect size combination with random effect modeling was used for obtaining differentially expressed genes (DEGs). Network construction was done for hub genes and pathway enrichment analysis. Our meta-analysis identified a total of 1,878 significant DEGs among the datasets, which when subjected to enrichment analysis suggested inflammation–coagulation–hypoxemia convolutions in COVID-19 pathogenesis. The top hub genes of our study such as tumor protein 53 (TP53), lysine acetyltransferase 2B (KAT2B), DExH-box helicase 9 (DHX9), REL-associated protein (RELA), RING-box protein 1 (RBX1), and proteasome 20S subunit beta 2 (PSMB2) gave insights into the genes known to be participating in the host–virus interactions that could pave the way to understand the various strategies deployed by the virus to improve its replication and spreading.

scholarly journals DNA methylome signatures as epigenetic biomarkers of hexanal associated with lung toxicity

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10779
Author(s):  
Yoon Cho ◽  
Mi-Kyung Song ◽  
Jae-Chun Ryu
Keyword(s):  
Dna Methylation ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Environmental Chemicals ◽  
Receptor Interaction ◽  
Integrated Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Epigenetic Biomarkers

Background Numerous studies have investigated the relationship of environmental exposure, epigenetic effects, and human diseases. These linkages may contribute to the potential toxicity mechanisms of environmental chemicals. Here, we investigated the epigenetic pulmonary response of hexanal, a major indoor irritant, following inhalation exposure in F-344 rats. Methods Based on DNA methylation profiling in gene promoter regions, we identified hexanal-characterized methylated sites and target genes using an unpaired t-test with a fold-change cutoff of ≥ 3.0 and a p-value < 0.05. We also conducted an integrated analysis of DNA methylation and mRNA expression data to identify core anti-correlated target genes of hexanal exposure. To further investigate the potential key biological processes and pathways of core DNA methylated target genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. Results Thirty-six dose-dependent methylated genes and anti-correlated target genes of DNA methylation and mRNA in lung tissue of hexanal exposed F-344 rats were identified. These genes were involved in diverse biological processes such as neuroactive ligand-receptor interaction, protein kinase cascade, and intracellular signaling cascade associated with pulmonary toxicity. These results suggest that novel DNA methylation-based epigenetic biomarkers of exposure to hexanal and elucidate the potential pulmonary toxicological mechanisms of action of hexanal.

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