scholarly journals CogNet: classification of gene expression data based on ranked active-subnetwork-oriented KEGG pathway enrichment analysis

2021 ◽  
Vol 7 ◽  
pp. e336
Author(s):  
Malik Yousef ◽  
Ege Ülgen ◽  
Osman Uğur Sezerman
Keyword(s):  
Gene Expression ◽  
Gene Selection ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Biological Knowledge ◽  
Pathway Enrichment Analysis ◽  
Biologically Relevant ◽  
Pathway Enrichment ◽  
Kegg Pathways

Most of the traditional gene selection approaches are borrowed from other fields such as statistics and computer science, However, they do not prioritize biologically relevant genes since the ultimate goal is to determine features that optimize model performance metrics not to build a biologically meaningful model. Therefore, there is an imminent need for new computational tools that integrate the biological knowledge about the data in the process of gene selection and machine learning. Integrative gene selection enables incorporation of biological domain knowledge from external biological resources. In this study, we propose a new computational approach named CogNet that is an integrative gene selection tool that exploits biological knowledge for grouping the genes for the computational modeling tasks of ranking and classification. In CogNet, the pathfindR serves as the biological grouping tool to allow the main algorithm to rank active-subnetwork-oriented KEGG pathway enrichment analysis results to build a biologically relevant model. CogNet provides a list of significant KEGG pathways that can classify the data with a very high accuracy. The list also provides the genes belonging to these pathways that are differentially expressed that are used as features in the classification problem. The list facilitates deep analysis and better interpretability of the role of KEGG pathways in classification of the data thus better establishing the biological relevance of these differentially expressed genes. Even though the main aim of our study is not to improve the accuracy of any existing tool, the performance of the CogNet outperforms a similar approach called maTE while obtaining similar performance compared to other similar tools including SVM-RCE. CogNet was tested on 13 gene expression datasets concerning a variety of diseases.

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

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

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.

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

2020 ◽  
Author(s):  
Zhiqiang Liu ◽  
Bolong Wang
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Kegg Pathway ◽  
Inflammatory Diseases ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Pharmacological Effects ◽  
Ppi Network ◽  
Pathway Enrichment ◽  
Pharmacological Mechanism

Abstract Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

scholarly journals Transcriptomic analysis of Procambarus clarkii affected by “Black May” disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guoqing Shen ◽  
Xiao Zhang ◽  
Jie Gong ◽  
Yang Wang ◽  
Pengdan Huang ◽  
...  
Keyword(s):  
Procambarus Clarkii ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Apoptosis Pathway ◽  
Pathway Enrichment ◽  
Cellular Processes ◽  
Expression Of Genes ◽  
Muscle Tissues

AbstractEach year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as “Black May” disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.

scholarly journals Serum MiR-4687-3p Has Potential for Diagnosis and Carcinogenesis in Non-small Cell Lung Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Man Liu ◽  
Qiufang Si ◽  
Songyun Ouyang ◽  
Zhigang Zhou ◽  
Meng Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Validation Cohort ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Pathway Enrichment Analysis ◽  
Small Cell Lung ◽  
Invasion And Migration ◽  
Pathway Enrichment ◽  
And Migration

The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, n = 10; the healthy, n = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, n = 30; the healthy, n = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543–0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues (p &lt; 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-β signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.

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.

MetENP/MetENPWeb: An R package and web application for metabolomics enrichment and pathway analysis in Metabolomics Workbench

2020 ◽  
Author(s):  
Kumari Sonal Choudhary ◽  
Eoin Fahy ◽  
Kevin Coakley ◽  
Manish Sud ◽  
Mano R Maurya ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Web Application ◽  
Enrichment Analysis ◽  
R Package ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Kegg Pathways ◽  
Link Type ◽  
Species Specific ◽  
User Friendly

ABSTRACTWith the advent of high throughput mass spectrometric methods, metabolomics has emerged as an essential area of research in biomedicine with the potential to provide deep biological insights into normal and diseased functions in physiology. However, to achieve the potential offered by metabolomics measures, there is a need for biologist-friendly integrative analysis tools that can transform data into mechanisms that relate to phenotypes. Here, we describe MetENP, an R package, and a user-friendly web application deployed at the Metabolomics Workbench site extending the metabolomics enrichment analysis to include species-specific pathway analysis, pathway enrichment scores, gene-enzyme information, and enzymatic activities of the significantly altered metabolites. MetENP provides a highly customizable workflow through various user-specified options and includes support for all metabolite species with available KEGG pathways. MetENPweb is a web application for calculating metabolite and pathway enrichment analysis.Availability and ImplementationThe MetENP package is freely available from Metabolomics Workbench GitHub: (https://github.com/metabolomicsworkbench/MetENP), the web application, is freely available at (https://www.metabolomicsworkbench.org/data/analyze.php)

scholarly journals Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

2017 ◽  
Vol 44 (2) ◽  
pp. 682-700 ◽  
Author(s):  
Lu Zhang ◽  
Lan-shan Huang ◽  
Gang Chen ◽  
Zhen-bo Feng
Keyword(s):  
Digestive Tract ◽  
Digestive System ◽  
Kegg Pathway ◽  
Univariate Analysis ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Clinical Value ◽  
Go Annotation ◽  
Pathway Enrichment ◽  
Target Mrnas

Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

scholarly journals UBE2T Contributes to the Prognosis of Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 27 ◽  
Author(s):  
Xiaoyuan Wang ◽  
Yang Liu ◽  
Xue Leng ◽  
Kui Cao ◽  
Wentao Sun ◽  
...  
Keyword(s):  
High Risk ◽  
Squamous Cell ◽  
Kegg Pathway ◽  
Risk Group ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Cox Regression Analysis ◽  
Gene Signatures ◽  
Pathway Enrichment

Background: The ubiquitin-conjugating enzyme E2 T (UBE2T) has been shown to contribute to several types of cancer. However, no publication has reported its implication in esophageal squamous cell cancer (ESCC).Methods: We explored several public databases, including The Cancer Genome Atlas (TCGA), Oncomine, and gene expression Omnibus (GEO). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were adopted to explore involved signaling pathways. We used R software to develop prognostic gene signatures with the LASSO and stepwise Cox regression analysis, separately. Immunohistochemistry staining was performed to detect UBE2T in 90 ESCC patients, followed by survival analysis. We also used an R package pRRophetic to evaluate chemotherapy sensitivity for the TCGA–ESCC cohort.Results: We found significantly increased UBE2T transcript levels and DNA copy numbers in ESCC tissues. UBE2T was associated with the p53 signaling pathway, cell cycle, Fanconi anemia pathway, and DNA replication, as indicated by Go, KEGG pathway enrichment analysis. These pathways were also upregulated in ESCC. The prognostic signatures with UBE2T-associated genes could stratify ESCC patients into low- and high-risk groups with significantly different overall survival in the TCGA–ESCC cohort. We also validated the association of UBE2T with unfavorable survival in 90 ESCC patients recruited for this study. Moreover, we found that the low-risk group was significantly more sensitive to chemotherapy than the high-risk group.Conclusions: UBE2T is involved in the development of ESCC, and gene signatures derived from UBE2T-associated genes are predictive of prognosis in ESCC.

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