scholarly journals Identification of Unique Key miRNAs, TFs, and mRNAs in Virulent MTB Infection Macrophages by Network Analysis

2021 ◽  
Vol 23 (1) ◽  
pp. 382
Author(s):  
Tingting Zhu ◽  
Han Liu ◽  
Li Su ◽  
Ali Dawood ◽  
Changmin Hu ◽  
...  
Keyword(s):  
Network Analysis ◽  
Target Genes ◽  
Immune Escape ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Immune Defense ◽  
Differentially Expressed ◽  
Acute Monocytic Leukemia ◽  
Pathway Enrichment Analysis ◽  
Monocytic Leukemia

Although Mycobacterium tuberculosis (MTB) has existed for thousands of years, its immune escape mechanism remains obscure. Increasing evidence signifies that microRNAs (miRNAs) play pivotal roles in the progression of tuberculosis (TB). RNA sequencing was used to sequence miRNAs in human acute monocytic leukemia cells (THP-1) infected by the virulent MTB-1458 strain and the avirulent vaccine strain Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Sets of differentially expressed miRNAs (DE-miRNAs) between MTB-1458/BCG-infected groups and uninfected groups were identified, among which 18 were differentially expressed only in the MTB-1458-infected THP-1 group. Then, 13 transcription factors (TFs) and 81 target genes of these 18 DE-miRNAs were matched. Gene Ontology classification as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the candidate targets were predominantly involved in apoptotic-associated and interferon-γ-mediated signaling pathways. A TF-miRNA-mRNA interaction network was constructed to analyze the relationships among these 18 DE-miRNAs and their targets and TFs, as well as display the hub miRNAs, TFs, and target genes. Considering the degrees from network analysis and the reported functions, this study focused on the BHLHE40-miR-378d-BHLHE40 regulation axis and confirmed that BHLHE40 was a target of miR-378d. This cross-talk among DE-miRNAs, mRNAs, and TFs might be an important feature in TB, and the findings merited further study and provided new insights into immune defense and evasion underlying host-pathogen interactions.

Bioinformatics Analysis Reveals Functions of MicroRNAs in Rice Under the Drought Stress

2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen
Keyword(s):  
Drought Stress ◽  
Target Genes ◽  
Hot Spot ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Promising Tool ◽  
Differentially Expressed Mirnas ◽  
Aba Biosynthesis

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.

scholarly journals Decoding the molecular mechanism of parthenocarpy in Musa spp. through protein–protein interaction network

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suthanthiram Backiyarani ◽  
Rajendran Sasikala ◽  
Simeon Sharmiladevi ◽  
Subbaraya Uma
Keyword(s):  
Candidate Genes ◽  
Protein Interaction ◽  
Target Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Auxin Signaling ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
The Difference

AbstractBanana, one of the most important staple fruit among global consumers is highly sterile owing to natural parthenocarpy. Identification of genetic factors responsible for parthenocarpy would facilitate the conventional breeders to improve the seeded accessions. We have constructed Protein–protein interaction (PPI) network through mining differentially expressed genes and the genes used for transgenic studies with respect to parthenocarpy. Based on the topological and pathway enrichment analysis of proteins in PPI network, 12 candidate genes were shortlisted. By further validating these candidate genes in seeded and seedless accession of Musa spp. we put forward MaAGL8, MaMADS16, MaGH3.8, MaMADS29, MaRGA1, MaEXPA1, MaGID1C, MaHK2 and MaBAM1 as possible target genes in the study of natural parthenocarpy. In contrary, expression profile of MaACLB-2 and MaZEP is anticipated to highlight the difference in artificially induced and natural parthenocarpy. By exploring the PPI of validated genes from the network, we postulated a putative pathway that bring insights into the significance of cytokinin mediated CLAVATA(CLV)–WUSHEL(WUS) signaling pathway in addition to gibberellin mediated auxin signaling in parthenocarpy. Our analysis is the first attempt to identify candidate genes and to hypothesize a putative mechanism that bridges the gaps in understanding natural parthenocarpy through PPI network.

scholarly journals Network Pharmacology and Molecular Docking Suggest the Mechanism for Biological Activity of Rosmarinic Acid

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Minglong Guan ◽  
Lan Guo ◽  
Hengli Ma ◽  
Huimei Wu ◽  
Xiaoyun Fan
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Rosmarinic Acid ◽  
Target Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis

Rosmarinic acid (RosA) is a natural phenolic acid compound, which is mainly extracted from Labiatae and Arnebia. At present, there is no systematic analysis of its mechanism. Therefore, we used the method of network pharmacology to analyze the mechanism of RosA. In our study, PubChem database was used to search for the chemical formula and the Chemical Abstracts Service (CAS) number of RosA. Then, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to evaluate the pharmacodynamics of RosA, and the Comparative Toxicogenomics Database (CTD) was used to identify the potential target genes of RosA. In addition, the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of target genes were carried out by using the web-based gene set analysis toolkit (WebGestalt). At the same time, we uploaded the targets to the STRING database to obtain the protein interaction network. Then, we carried out a molecular docking about targets and RosA. Finally, we used Cytoscape to establish a visual protein-protein interaction network and drug-target-pathway network and analyze these networks. Our data showed that RosA has good biological activity and drug utilization. There are 55 target genes that have been identified. Then, the bioinformatics analysis and network analysis found that these target genes are closely related to inflammatory response, tumor occurrence and development, and other biological processes. These results demonstrated that RosA can act on a variety of proteins and pathways to form a systematic pharmacological network, which has good value in drug development and utilization.

scholarly journals System Analysis of MIRNAs in Maize Internode Elongation

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 417
Author(s):  
Chuanxi Peng ◽  
Xing Wang ◽  
Tianyu Feng ◽  
Rui He ◽  
Mingcai Zhang ◽  
...  
Keyword(s):  
Target Genes ◽  
System Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Internode Elongation ◽  
Differentially Expressed Mirnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.

scholarly journals Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Wenqing Nai ◽  
Diane Threapleton ◽  
Jingbo Lu ◽  
Kewei Zhang ◽  
Hongyuan Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Transforming Growth Factor Β ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Atheromatous Plaques

Abstract Atherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the “immune response” and “muscle contraction” were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the “FcεRI-mediated signaling pathway”, while down-regulated genes were significantly enriched in the “transforming growth factor-β signaling pathway”. Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma.

scholarly journals Identification of hydatidosis-related modules and key regulatory genes

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9280
Author(s):  
Jijun Song ◽  
Mingxin Song
Keyword(s):  
Transcription Factors ◽  
Signaling Pathway ◽  
Target Genes ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Bmp Signaling ◽  
Differentially Expressed ◽  
Regulatory Effects

Background Echinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection. Method First, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism. Results A total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine. Conclusion The results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.

scholarly journals VIRdb: a comprehensive database for interactive analysis of genes/proteins involved in the pathogenesis of vitiligo

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9119
Author(s):  
Priyansh Srivastava ◽  
Alakto Choudhury ◽  
Mehak Talwar ◽  
Sabyasachi Mohanty ◽  
Priyanka Narad ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Protein Level ◽  
Skin Color ◽  
Systems Approach ◽  
Basal Layer ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Gene Interaction Network

Vitiligo is a chronic asymptomatic disorder affecting melanocytes from the basal layer of the epidermis which leads to a patchy loss of skin color. Even though it is one of the neglected disease conditions, people suffering from vitiligo are more prone to psychological disorders. As of now, various studies have been done in order to project auto-immune implications as the root cause. To understand the complexity of vitiligo, we propose the Vitiligo Information Resource (VIRdb) that integrates both the drug-target and systems approach to produce a comprehensive repository entirely devoted to vitiligo, along with curated information at both protein level and gene level along with potential therapeutics leads. These 25,041 natural compounds are curated from Natural Product Activity and Species Source Database. VIRdb is an attempt to accelerate the drug discovery process and laboratory trials for vitiligo through the computationally derived potential drugs. It is an exhaustive resource consisting of 129 differentially expressed genes, which are validated through gene ontology and pathway enrichment analysis. We also report 22 genes through enrichment analysis which are involved in the regulation of epithelial cell differentiation. At the protein level, 40 curated protein target molecules along with their natural hits that are derived through virtual screening. We also demonstrate the utility of the VIRdb by exploring the Protein–Protein Interaction Network and Gene–Gene Interaction Network of the target proteins and differentially expressed genes. For maintaining the quality and standard of the data in the VIRdb, the gold standard in bioinformatics toolkits like Cytoscape, Schrödinger’s GLIDE, along with the server installation of MATLAB, are used for generating results. VIRdb can be accessed through “http://www.vitiligoinfores.com/”.

scholarly journals Mechanism of YuPingFeng in the Treatment of COPD Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yunhong Yin ◽  
Jianyu Liu ◽  
Mengyu Zhang ◽  
Rui Li ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Target Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Signalling Pathways ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Herbal Formula ◽  
Pathway Enrichment ◽  
Topological Parameters

YuPingFeng (YPF) granules are a classic herbal formula extensively used in clinical practice in China for the treatment of COPD. However, the pathological mechanisms of YPF in COPD remain undefined. In the present research, a network pharmacology-based strategy was implemented to elucidate the underlying multicomponent, multitarget, and multipathway modes of action of YPF against COPD. First, we identified putative YPF targets based on TCMSP databases and constructed a network containing interactions between putative YPF targets and known therapeutic targets of COPD. Next, two topological parameters, “degree” and “closeness,” were calculated to identify target genes in the network. The major hubs were imported to the MetaCore database for pathway enrichment analysis. In total, 23 YPF active ingredients and 83 target genes associated with COPD were identified. Through protein interaction network analysis, 26 genes were identified as major hubs due to their topological importance. GO and KEGG enrichment analysis results revealed YPF to be mainly associated with the response to glucocorticoids and steroid hormones, with apoptotic and HIF-1 signalling pathways being dominant and correlative pathways. The promising utility of YPF in the treatment of COPD has been demonstrated by a network pharmacology approach.

scholarly journals Genome-Wide Analysis of Coding and Long Non-Coding RNAs Involved in Cuticular Wax Biosynthesis in Cabbage (Brassica oleracea L. var. capitata)

2019 ◽  
Vol 20 (11) ◽  
pp. 2820 ◽  
Author(s):  
Xiaowei Zhu ◽  
Xiang Tai ◽  
Yunying Ren ◽  
Jinxiu Chen ◽  
Tianyue Bo
Keyword(s):  
Molecular Basis ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Cuticular Wax ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Genome Wide ◽  
Important Trait ◽  
Electron Microscope Analysis ◽  
Type Gene

Cuticular wax is a mixture of very long chain fatty acids (VLCFAs) and their derivatives, which determines vital roles for plant growth. In cabbage, the cuticular wax content of leaf blades is an important trait influencing morphological features of the head. Understanding the molecular basis of cuticular wax biosynthesis can help breeders develop high quality cabbage varieties. Here, we characterize a cabbage non-wax glossy (nwgl) plant, which exhibits glossy green phenotype. Cryo-scanning electron microscope analysis showed abnormal wax crystals on the leaf surfaces of nwgl plants. Cuticular wax composition analyzed by GC-MS displayed severely decreased in total wax loads, and individual wax components in nwgl leaves. We delimited the NWGL locus into a 99-kb interval between the at004 marker and the end of chromosome C08 through fine mapping. By high-throughput RNA sequencing, we identified 1247 differentially expressed genes (DEGs) and 148 differentially expressed lncRNAs in nwgl leaves relative to the wild-type. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the DEGs and cis-regulated target genes for differentially expressed lncRNAs were significantly enriched in wax and lipid biosynthetic or metabolic processes. Our results provide the novel foundation to explore the complex molecular basis of cuticular wax biosynthesis.

scholarly journals Investigation of the miRNA and mRNA Coexpression Network and Their Prognostic Value in Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Hao Zhang ◽  
Xi Chen ◽  
Yufeng Yuan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Ontology ◽  
Cell Adhesion ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Positive Regulation ◽  
Differentially Expressed Mirnas ◽  
Cell Cell

Purpose. To identify pivotal differentially expressed miRNAs and genes and construct their regulatory network in hepatocellular carcinoma. Methods. mRNA (GSE101728) and microRNA (GSE108724) microarray datasets were obtained from the NCBI Gene Expression Omnibus (GEO) database. Then, we identified the differentially expressed miRNAs and mRNAs. Sequentially, transcription factor enrichment and gene ontology (GO) enrichment analysis for miRNA were performed. Target genes of these differential miRNAs were obtained using packages in R language ( R package multiMiR). After that, downregulated miRNAs were matched with target mRNAs which were upregulated, while upregulated miRNAs were paired with downregulated target mRNA using scripts written in Perl. An miRNA-mRNA network was constructed and visualized in Cytoscape software. For miRNAs in the network, survival analysis was performed. And for genes in the network, we did gene ontology (GO) and KEGG pathway enrichment analysis. Results. A total of 35 miRNAs and 295 mRNAs were involved in the network. These differential genes were enriched in positive regulation of cell-cell adhesion, positive regulation of leukocyte cell-cell adhesion, and so on. Eight differentially expressed miRNAs were found to be associated with the OS of patients with HCC. Among which, miR-425 and miR-324 were upregulated while the other six, including miR-99a, miR-100, miR-125b, miR-145, miR-150, and miR-338, were downregulated. Conclusion. In conclusion, these results can provide a potential research direction for further studies about the mechanisms of how miRNA affects malignant behavior in hepatocellular carcinoma.

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