scholarly journals Modular network inference between miRNA–mRNA expression profiles using weighted co-expression network analysis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nisar Wani ◽  
Debmalya Barh ◽  
Khalid Raza
Keyword(s):  
Network Analysis ◽  
Mrna Expression ◽  
Mirna Expression ◽  
Regulatory Networks ◽  
Network Inference ◽  
Expression Profiles ◽  
Interaction Network ◽  
Pathway Enrichment Analysis ◽  
Expression Data ◽  
Cancer Data

Abstract Connecting transcriptional and post-transcriptional regulatory networks solves an important puzzle in the elucidation of gene regulatory mechanisms. To decipher the complexity of these connections, we build co-expression network modules for mRNA as well as miRNA expression profiles of breast cancer data. We construct gene and miRNA co-expression modules using the weighted gene co-expression network analysis (WGCNA) method and establish the significance of these modules (Genes/miRNAs) for cancer phenotype. This work also infers an interaction network between the genes of the turquoise module from mRNA expression data and hubs of the turquoise module from miRNA expression data. A pathway enrichment analysis using a miRsystem web tool for miRNA hubs and some of their targets, reveal their enrichment in several important pathways associated with the progression of cancer.

scholarly journals Identification of Subtype Specific miRNA-mRNA Functional Regulatory Modules in Matched miRNA-mRNA Expression Data: Multiple Myeloma as a Case

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Yunpeng Zhang ◽  
Wei Liu ◽  
Yanjun Xu ◽  
Chunquan Li ◽  
Yingying Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mrna Expression ◽  
Regulatory Networks ◽  
Mirna Target ◽  
Expression Profiles ◽  
Biological Data ◽  
Expression Data ◽  
Target Information ◽  
Mrna Expression Data ◽  
Regulatory Modules

Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it is important to identify subtype specific miRNA-mRNA modules. In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs) through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data. We applied our method on a heterogeneous disease, multiple myeloma (MM), to identify MM subtype specific MFRMs. The constructed miRNA-mRNA regulatory networks provide modular outlook at subtype specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes. These subtype specific MFRMs may aid in the further elucidation of the pathogenesis of each subtype and may serve to guide MM subtype diagnosis and treatment.

scholarly journals ­­Ensemble-based network aggregation improves the accuracy of gene network reconstruction

2013 ◽  
Author(s):  
Jeffrey D. Allen ◽  
Yang Xie ◽  
Guanghua Xiao
Keyword(s):  
Mrna Expression ◽  
Regulatory Networks ◽  
Network Inference ◽  
R Package ◽  
Network Reconstruction ◽  
Specific Gene ◽  
Expression Data ◽  
Mrna Expression Data ◽  
Network Aggregation ◽  
Context Specific

Reverse engineering approaches to construct context-specific gene regulatory networks (GRNs) based on genome-wide mRNA expression data have led to significant biological findings. However, the reliability and reproducibility of the reconstructed GRNs needs to be improved. Here, we propose an ensemble-based network aggregation approach to improve the accuracy of the network topology constructed from mRNA expression data. To evaluate the performance of different approaches, we created dozens of simulated networks and also tested our methods on three Escherichia coli datasets. We demonstrate three novel applications from this development. First, bootstrapping can be done on the available samples, turning any network reconstruction approach into an ensemble method. Second, this aggregation approach can be used to combine GRNs from different network inference methods, creating a novel network reconstruction approach that consistently outperforms any constituent method. Third, the approach can be used to effectively integrate GRNs constructed from different studies – producing more accurate networks. We are releasing an implementation of these techniques as an R package “ENA” which is able to run network inference in parallel across multiple servers. We made all of the code and data used in our simulations and analysis available online at https://github.com/QBRC/ENA-Research to ensure the reproducibility of our results.

scholarly journals ­­Ensemble-based network aggregation improves the accuracy of gene network reconstruction

2013 ◽  
Author(s):  
Jeffrey D. Allen ◽  
Yang Xie ◽  
Guanghua Xiao
Keyword(s):  
Mrna Expression ◽  
Regulatory Networks ◽  
Network Inference ◽  
R Package ◽  
Network Reconstruction ◽  
Specific Gene ◽  
Expression Data ◽  
Mrna Expression Data ◽  
Network Aggregation ◽  
Context Specific

Reverse engineering approaches to construct context-specific gene regulatory networks (GRNs) based on genome-wide mRNA expression data have led to significant biological findings. However, the reliability and reproducibility of the reconstructed GRNs needs to be improved. Here, we propose an ensemble-based network aggregation approach to improve the accuracy of the network topology constructed from mRNA expression data. To evaluate the performance of different approaches, we created dozens of simulated networks and also tested our methods on three Escherichia coli datasets. We demonstrate three novel applications from this development. First, bootstrapping can be done on the available samples, turning any network reconstruction approach into an ensemble method. Second, this aggregation approach can be used to combine GRNs from different network inference methods, creating a novel network reconstruction approach that consistently outperforms any constituent method. Third, the approach can be used to effectively integrate GRNs constructed from different studies – producing more accurate networks. We are releasing an implementation of these techniques as an R package “ENA” which is able to run network inference in parallel across multiple servers. We made all of the code and data used in our simulations and analysis available online at https://github.com/QBRC/ENA-Research to ensure the reproducibility of our results.

Genome-Wide Identification of differently expressed lncRNAs, mRNAs, and circRNAs in patients with osteoarthritis

2020 ◽  
Vol 15 ◽  
Author(s):  
Yeqing Sun ◽  
Lei Chen ◽  
Yingqi Zhang ◽  
Jincheng Zhang ◽  
Shashi Ranjan Tiwari
Keyword(s):  
Regulatory Networks ◽  
Expression Profiles ◽  
Interleukin 1 ◽  
Interaction Network ◽  
Circular Rna ◽  
Negative Regulation ◽  
Differentially Expressed ◽  
Positive Regulation ◽  
Proteinprotein Interaction ◽  
Differently Expressed Genes

Background: Osteoarthritis (OA), one of the most important causes leading to joint disability, was considered as an untreatable disease. A series of genes were reported to regulate the pathogenesis of OA, including microRNAs, Long non-coding RNAs and Circular RNA. So far, the expression profiles and functions of lncRNAs, mRNAs, and circRNAs in OA are not fully understood. Objective: The present study aimed to identify differently expressed genes in OA. Methods: The present study conducted RNA-seq to identify differently expressed genes in OA. Ontology (GO) analysis was used to analysis the Molecular Function and Biological Process. KEGG pathway analysis was used to perform the differentially expressed lncRNAs in biological pathways. Results: Hierarchical clustering revealed a total of 943 mRNAs, 518 lncRNAs, and 300 circRNAs were dysregulated in OA compared to normal samples. Furthermore, we constructed differentially expressed mRNAs mediated proteinprotein interaction network, differentially expressed lncRNAs mediated trans regulatory networks, and competitive endogenous RNA (ceRNA) to reveal the interaction among these genes in OA. Bioinformatics analysis revealed these dysregulated genes were involved in regulating multiple biological processes, such as wound healing, negative regulation of ossification, sister chromatid cohesion, positive regulation of interleukin-1 alpha production, sodium ion transmembrane transport, positive regulation of cell migration, and negative regulation of inflammatory response. To the best of our knowledge, this study for the first time revealed the expression pattern of mRNAs, lncRNAs and circRNAs in OA. Conclusion: This study provided novel information to validate these differentially expressed RNAs may be as possible biomarkers and targets in OA.

Predicting functional circular RNA-based competitive endogenous RNA network in gastric carcinoma using novel bioinformatics analysis

2021 ◽  
pp. 153537022110487
Author(s):  
Zirui Zhu ◽  
Rui Huang ◽  
Baojun Huang
Keyword(s):  
Messenger Rna ◽  
Expression Profiles ◽  
Clinical Stage ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Rank Aggregation ◽  
Circular Rnas ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Competitive Endogenous Rna

Gastric cancer (GC) remains one of the most prevalent types of malignancies worldwide, and also one of the most reported lethal tumor-related diseases. Circular RNAs (circRNAs) have been certified to be trapped in multiple aspects of GC pathogenesis. Yet, the mechanism of this regulation is mostly undefined. This research is designed to discover the vital circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in GC. Expression profiles with diverse levels including circRNAs, miRNAs, and mRNAs were all determined using microarray public datasets from Gene Expression Ominous (GEO). The differential circRNAs expressions were recognized against the published robust rank aggregation algorithm. Besides, a circRNA-based competitive endogenous RNA (ceRNA) interaction network was visualized via Cytoscape software (version 3.8.0). Functional and pathway enrichment analysis associated with differentially expressed targeted mRNAs were conducted using Cytoscape and an online bioinformatics database. Furthermore, an interconnected protein–protein interaction association network which consisted of 51 mRNAs was predicted, and hub genes were screened using STRING and CytoHubba. Then, several hub genes were chosen to explore their expression associated with survival rate and clinical stage in GEPIA and Kaplan-Meier Plotter databases. Finally, a carefully designed circRNA-related ceRNA regulatory subnetwork including four circRNAs, six miRNAs, and eight key hub genes was structured using the online bioinformatics tool.

PAGeneRN

2020 ◽  
pp. 1052-1075 ◽  
Author(s):  
Dina Elsayad ◽  
A. Ali ◽  
Howida A. Shedeed ◽  
Mohamed F. Tolba
Keyword(s):  
Gene Expression ◽  
Data Analysis ◽  
Network Analysis ◽  
Gene Regulatory Network ◽  
Gene Expression Data ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Expression Data ◽  
Gene Expression Data Analysis ◽  
Gene Regulatory

The gene expression analysis is an important research area of Bioinformatics. The gene expression data analysis aims to understand the genes interacting phenomena, gene functionality and the genes mutations effect. The Gene regulatory network analysis is one of the gene expression data analysis tasks. Gene regulatory network aims to study the genes interactions topological organization. The regulatory network is critical for understanding the pathological phenotypes and the normal cell physiology. There are many researches that focus on gene regulatory network analysis but unfortunately some algorithms are affected by data size. Where, the algorithm runtime is proportional to the data size, therefore, some parallel algorithms are presented to enhance the algorithms runtime and efficiency. This work presents a background, mathematical models and comparisons about gene regulatory networks analysis different techniques. In addition, this work proposes Parallel Architecture for Gene Regulatory Network (PAGeneRN).

scholarly journals Protein–Protein Interaction Network Analysis Reveals Several Diseases Highly Associated with Polycystic Ovarian Syndrome

2019 ◽  
Vol 20 (12) ◽  
pp. 2959 ◽  
Author(s):  
Balqis Ramly ◽  
Nor Afiqah-Aleng ◽  
Zeti-Azura Mohamed-Hussein
Keyword(s):  
Network Analysis ◽  
Protein Interaction ◽  
Ribosome Biogenesis ◽  
Antigen Processing ◽  
Polycystic Ovarian Syndrome ◽  
Interaction Network ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Ovarian Syndrome

Based on clinical observations, women with polycystic ovarian syndrome (PCOS) are prone to developing several other diseases, such as metabolic and cardiovascular diseases. However, the molecular association between PCOS and these diseases remains poorly understood. Recent studies showed that the information from protein–protein interaction (PPI) network analysis are useful in understanding the disease association in detail. This study utilized this approach to deepen the knowledge on the association between PCOS and other diseases. A PPI network for PCOS was constructed using PCOS-related proteins (PCOSrp) obtained from PCOSBase. MCODE was used to identify highly connected regions in the PCOS network, known as subnetworks. These subnetworks represent protein families, where their molecular information is used to explain the association between PCOS and other diseases. Fisher’s exact test and comorbidity data were used to identify PCOS–disease subnetworks. Pathway enrichment analysis was performed on the PCOS–disease subnetworks to identify significant pathways that are highly involved in the PCOS–disease associations. Migraine, schizophrenia, depressive disorder, obesity, and hypertension, along with twelve other diseases, were identified to be highly associated with PCOS. The identification of significant pathways, such as ribosome biogenesis, antigen processing and presentation, and mitophagy, suggest their involvement in the association between PCOS and migraine, schizophrenia, and hypertension.

scholarly journals In Silico Discovery of Candidate Drugs against Covid-19

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 404 ◽  
Author(s):  
Claudia Cava ◽  
Gloria Bertoli ◽  
Isabella Castiglioni
Keyword(s):  
Gene Expression ◽  
In Silico ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Basic Mechanism ◽  
Cell Receptor ◽  
The Cancer Genome Atlas ◽  
Pathway Enrichment Analysis

Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. It plays a key role in the access of the virus into the cell to produce the final infection. In the present study we investigated in silico the basic mechanism of ACE2 in the lung and provided evidences for new potentially effective drugs for Covid-19. Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of ACE2-correlated genes. We constructed a protein-protein interaction network containing the genes co-expressed with ACE2. Finally, we focused on the genes in the network that are already associated with known drugs and evaluated their role for a potential treatment of Covid-19. Our results demonstrate that the genes correlated with ACE2 are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity. We identified a network of 193 genes, 222 interactions and 36 potential drugs that could have a crucial role. Among possible interesting drugs for Covid-19 treatment, we found Nimesulide, Fluticasone Propionate, Thiabendazole, Photofrin, Didanosine and Flutamide.

scholarly journals Integrated Analysis of microRNA and mRNA Expression Profiles: An Attempt to Disentangle the Complex Interaction Network in Attention Deficit Hyperactivity Disorder

2019 ◽  
Vol 9 (10) ◽  
pp. 288
Author(s):  
Nicoletta Nuzziello ◽  
Francesco Craig ◽  
Marta Simone ◽  
Arianna Consiglio ◽  
Flavio Licciulli ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Mrna Expression ◽  
Attention Deficit ◽  
Expression Profiles ◽  
Interaction Network ◽  
Small Sample ◽  
Integrated Analysis ◽  
Children With Adhd ◽  
Pathway Enrichment ◽  
Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood-onset neurodevelopmental disorder, whose etiology and pathogenesis are still largely unknown. In order to uncover novel regulatory networks and molecular pathways possibly related to ADHD, we performed an integrated miRNA and mRNA expression profiling analysis in peripheral blood samples of children with ADHD and age-matched typically developing (TD) children. The expression levels of 13 miRNAs were evaluated with microfluidic qPCR, and differentially expressed (DE) mRNAs were detected on an Illumina HiSeq 2500 genome analyzer. The miRNA targetome was identified using an integrated approach of validated and predicted interaction data extracted from seven different bioinformatic tools. Gene Ontology (GO) and pathway enrichment analyses were carried out. Results showed that six miRNAs (miR-652-3p, miR-942-5p, let-7b-5p, miR-181a-5p, miR-320a, and miR-148b-3p) and 560 genes were significantly DE in children with ADHD compared to TD subjects. After correction for multiple testing, only three miRNAs (miR-652-3p, miR-148b-3p, and miR-942-5p) remained significant. Genes known to be associated with ADHD (e.g., B4GALT2, SLC6A9 TLE1, ANK3, TRIO, TAF1, and SYNE1) were confirmed to be significantly DE in our study. Integrated miRNA and mRNA expression data identified critical key hubs involved in ADHD. Finally, the GO and pathway enrichment analyses of all DE genes showed their deep involvement in immune functions, reinforcing the hypothesis that an immune imbalance might contribute to the ADHD etiology. Despite the relatively small sample size, in this study we were able to build a complex miRNA-target interaction network in children with ADHD that might help in deciphering the disease pathogenesis. Validation in larger samples should be performed in order to possibly suggest novel therapeutic strategies for treating this complex disease.

scholarly journals Prediction and Validation of Hub Genes Associated with Colorectal Cancer by Integrating PPI Network and Gene Expression Data

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yongfu Xiong ◽  
Wenxian You ◽  
Rong Wang ◽  
Linglong Peng ◽  
Zhongxue Fu
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Advanced Tumor Stage ◽  
Ppi Network ◽  
Hub Genes ◽  
Clinical Value ◽  
Advanced Tumor

Although hundreds of colorectal cancer- (CRC-) related genes have been screened, the significant hub genes still need to be further identified. The aim of this study was to identify the hub genes based on protein-protein interaction network and uncover their clinical value. Firstly, 645 CRC patients’ data from the Tumor Cancer Genome Atlas were downloaded and analyzed to screen the differential expression genes (DEGs). And then, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed, and PPI network of the DEGs was constructed by Cytoscape software. Finally, four hub genes (CXCL3, ELF5, TIMP1, and PHLPP2) were obtained from four subnets and further validated in our clinical setting and TCGA dataset. The results showed that mRNA expression of CXCL3, ELF5, and TIMP1 was increased in CRC tissues, whereas PHLPP2 mRNA expression was decreased. More importantly, high expression of CXCL3, ELF5, and TIMP1 was significantly associated with lymphatic invasion, distance metastasis, and advanced tumor stage. In addition, a shorter overall survival was observed in patients with increased CXCL3, TIMP1, and ELF5 expression and decreased PHLPP2 expression. In conclusion, the four hub genes screened by our strategy could serve as novel biomarkers for prognosis prediction of CRC patients.

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