Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next-generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analyses of DEGs were performed. Then, a protein-protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst databaseswereused to construct the targeted microRNAs (miRNAs), transcription factors (TFs), and small drug molecules. Finally, receiver operating characteristic (ROC) curve analysis was used to validate the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process, and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8, and EFHC2 were selected. Cyclothiazide and rotigotinethe are predicted small drug molecules for IPF treatment. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Bioinformatics and Next-Generation Sequencing Data Analysis.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancers worldwide. Intense efforts have been made to elucidate the molecular pathogenesis, but the molecular mechanisms of PDAC are still not well understood. The purpose of this study is to further explore the molecular mechanism of PDAC through integrated bioinformatics analysis. Methods: To identify the candidate genes in the carcinogenesis and progression of PDAC, next-generation sequencing (NGS) data set GSE133684 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and Gene Ontology (GO) and pathway enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using Integrated Interactions Database (IID) interactome database and Cytoscape. Subsequently, miRNA-DEG regulatory network and TF-DEG regulatory network were constructed using miRNet database, NetworkAnalyst database, and Cytoscape software. The expression levels of hub genes were validated based on Kaplan-Meier analysis, expression analysis, stage analysis, mutation analysis, protein expression analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis. Results: A total of 463 DEGs were identified, consisting of 232 upregulated genes and 233 downregulated genes. The enriched GO terms and pathways of the DEGs include vesicle organization, secretory vesicle, protein dimerization activity, lymphocyte activation, cell surface, transferase activity, transferring phosphorus-containing groups, hemostasis, and adaptive immune system. Four hub genes (namely, cathepsin B [CCNB1], four-and-a-half LIM domains 2 (FHL2), major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) and tubulin beta 1 class VI (TUBB1)) were obtained via taking interaction of different analysis results. Conclusions: On the whole, the findings of this investigation enhance our understanding of the potential molecular mechanisms of PDAC and provide potential targets for further investigation.

Identification of biomarkers, pathways, and potential therapeutic targets for heart failure using next-generation sequencing data and bioinformatics analysis.

BACKGROUND: Heart failure (HF) is the most common cardiovascular diseases and the leading cause of cardiovascular diseases related deaths. Increasing molecular targets have been discovered for HF prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might aid the diagnosis and treatment of HF. METHODS: We searched next-generation sequencing (NGS) dataset (GSE161472) and identified differentially expressed genes (DEGs) by comparing 47 HF samples and 37 normal control samples using limma in R package. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g: Profiler database. The protein-protein interaction (PPI) network was plotted with Human Integrated Protein-Protein Interaction rEference (HiPPIE) and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. Then, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed by Cytoscape software. Finally, we performed receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes. RESULTS: A total of 930 DEGs, 464 upregulated genes and 466 downregulated genes, were identified in HF. GO and REACTOME pathway enrichment results showed that DEGs mainly enriched in localization, small molecule metabolic process, SARS-CoV infections, and the citric acid tricarboxylic acid (TCA) cycle and respiratory electron transport. After combining the results of the PPI network miRNA-hub gene regulatory network and TF-hub gene regulatory network, 10 hub genes were selected, including heat shock protein 90 alpha family class A member 1 (HSP90AA1), arrestin beta 2 (ARRB2), myosin heavy chain 9 (MYH9), heat shock protein 90 alpha family class B member 1 (HSP90AB1), filamin A (FLNA), epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), cullin 4A (CUL4A), YEATS domain containing 4 (YEATS4), and lysine acetyltransferase 2B (KAT2B). CONCLUSIONS: This discovery-driven study might be useful to provide a novel insight into the diagnosis and treatment of HF. However, more experiments are needed in the future to investigate the functional roles of these genes in HF.

Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity.

Background and Objectives: A subject with diabetes and obesity is a class of the metabolic disorder. The current investigation aimed to elucidate the potential biomarker and prognostic targets in subjects with diabetes and obesity. Materials and Methods: The next-generation sequencing (NGS) data of GSE132831 was downloaded from Gene Expression Omnibus (GEO) database. Functional enrichment analysis of DEGs was conducted with ToppGene. The protein-protein interactions network, module analysis, target gene-miRNA regulatory network and target gene-TF regulatory network were constructed and analyzed. Furthermore, hub genes were validated by receiver operating characteristic (ROC) analysis. A total of 872 DEGs, including 439 up-regulated genes and 433 down-regulated genes were observed. Results: Second, functional enrichment analysis showed that these DEGs are mainly involved in the axon guidance, neutrophil degranulation, plasma membrane bounded cell projection organization and cell activation. The top ten hub genes (MYH9, FLNA, DCTN1, CLTC, ERBB2, TCF4, VIM, LRRK2, IFI16 and CAV1) could be utilized as potential diagnostic indicators for subjects with diabetes and obesity. The hub genes were validated in subjects with diabetes and obesity. Conclusion: This investigation found effective and reliable molecular biomarkers for diagnosis and prognosis by integrated bioinformatics analysis, suggesting new and key therapeutic targets for subjects with diabetes and obesity.

Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus.

Background: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder. The aim of the present investigation was to identify gene signature specific to T2DM. Methods: The next generation sequencing (NGS) dataset GSE81608 was retrieved from the gene expression omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) between T2DM and normal controls. Then, Gene Ontology (GO) and pathway enrichment analysis, protein-protein interaction (PPI) network, modules, miRNA (micro RNA)-hub gene regulatory network construction and TF (transcription factor)-hub gene regulatory network construction, and topological analysis were performed. Receiver operating characteristic curve (ROC) analysis was also performed to verify the prognostic value of hub genes. Results: A total of 927 DEGs (461 were up regulated and 466 down regulated genes) were identified in T2DM. GO and REACTOME results showed that DEGs mainly enriched in protein metabolic process, establishment of localization, metabolism of proteins, and metabolism. The top centrality hub genes APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1 were screened out as the critical genes. ROC analysis provides prognostic value of hub genes. Conclusion: The potential crucial genes, especially APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1, might be linked with risk of T2DM. Our study provided novel insights of T2DM into genetics, molecular pathogenesis, and novel therapeutic targets.

Integrated bioinformatics analysis reveals novel key biomarkers in diabetic nephropathy.

Objectives: The underlying molecular mechanisms of diabetic nephropathy have yet not been investigated clearly. In this investigation, we aimed to identify key genes involved in the pathogenesis and prognosis of diabetic nephropathy. Methods: We downloaded next-generation sequencing data set GSE142025 from Gene Expression Omnibus database having 28 diabetic nephropathy samples and nine normal control samples. The differentially expressed genes between diabetic nephropathy and normal control samples were analyzed. Biological function analysis of the differentially expressed genes was enriched by Gene Ontology and REACTOME pathways. Then, we established the protein-protein interaction network, modules, miRNA-differentially expressed gene regulatory network and transcription factor-differentially expressed gene regulatory network. Hub genes were validated by using receiver operating characteristic curve analysis. Results: A total of 549 differentially expressed genes were detected including 275 upregulated and 274 downregulated genes. The biological process analysis of functional enrichment showed that these differentially expressed genes were mainly enriched in cell activation, integral component of plasma membrane, lipid binding, and biological oxidations. Analyzing the protein-protein interaction network, miRNA-differentially expressed gene regulatory network and transcription factor-differentially expressed gene regulatory network, we screened hub genes MDFI, LCK, BTK, IRF4, PRKCB, EGR1, JUN, FOS, ALB, and NR4A1 by the Cytoscape software. The receiver operating characteristic curve analysis confirmed that hub genes were of diagnostic value. Conclusions: Taken above, using integrated bioinformatics analysis, we have identified key genes and pathways in diabetic nephropathy, which could improve our understanding of the cause and underlying molecular events, and these key genes and pathways might be therapeutic targets for diabetic nephropathy.

Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis.

Type 1 diabetes mellitus (T1DM) is a metabolic disorder for which the underlying molecular mechanisms remain largely unclear. This investigation aimed to elucidate essential candidate genes and pathways in T1DM by integrated bioinformatics analysis. In this study, differentially expressed genes (DEGs) were analyzed using DESeq2 of R package from GSE162689 of the Gene Expression Omnibus (GEO). Gene ontology (GO) enrichment analysis, REACTOME pathway enrichment analysis, and construction and analysis of protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, and validation of hub genes were performed. A total of 952 DEGs (477 up regulated and 475 down regulated genes) were identified in T1DM. GO and REACTOME enrichment result results showed that DEGs mainly enriched in multicellular organism development, detection of stimulus, diseases of signal transduction by growth factor receptors and second messengers, and olfactory signaling pathway. The top hub genes such as MYC, EGFR, LNX1, YBX1, HSP90AA1, ESR1, FN1, TK1, ANLN and SMAD9 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. Receiver operating characteristic curve (ROC) analysis confirmed that these genes were significantly associated with T1DM. In conclusion, the identified DEGs, particularly the hub genes, strengthen the understanding of the advancement and progression of T1DM, and certain genes might be used as candidate target molecules to diagnose, monitor and treat T1DM.

Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis.

INTRODUCTION: Heart failure (HF) is a heterogeneous clinical syndrome and affects millions of people all over the world. HF occurs when the cardiac overload and injury, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental HF as well as to explore active drug molecules. METHODS: The expression profiling by high throughput sequencing of GSE141910 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which contained 366 samples, including 200 heart failure samples and 166 non heart failure samples. The raw data was integrated to find differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. Gene ontology (GO) and REACTOME enrichment analyses were performed via ToppGene; protein-protein interaction (PPI) networks of the DEGs was constructed based on data from the HiPPIE interactome database; modules analysis was performed; target gene-miRNA regulatory network and target gene-TF regulatory network were constructed and analyzed; hub genes were validated; molecular docking studies was performed. RESULTS: A total of 881 DEGs, including 442 up regulated genes and 439 down regulated genes were observed. Most of the DEGs were significantly enriched in biological adhesion, extracellular matrix, signaling receptor binding, secretion, intrinsic component of plasma membrane, signaling receptor activity, extracellular matrix organization and neutrophil degranulation. The top hub genes ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 were identified from the PPI network. Module analysis revealed that HF was associated with adaptive immune system and neutrophil degranulation. The target genes, miRNAs and TFs were identified from the target gene-miRNA regulatory network and target gene-TF regulatory network. Furthermore, receiver operating characteristic (ROC) curve analysis and RT-PCR analysis revealed that ESR1, PYHIN1, PPP2R2B, LCK, TP63, PCLAF, CFTR, TK1, ECT2 and FKBP5 might serve as prognostic, diagnostic biomarkers and therapeutic target for HF. The predicted targets of these active molecules were then confirmed. CONCLUSION: The current investigation identified a series of key genes and pathways that might be involved in the progression of HF, providing a new understanding of the underlying molecular mechanisms of HF.

Identification of Key Pathways and Genes in Obesity Using Bioinformatics Analysis and Molecular Docking Studies.

Obesity is an excess accumulation of body fat. Its progression rate has remained high in recent years. Therefore, the aim of this study was to diagnose important differentially expressed genes (DEGs) associated in its development, which may be used as novel biomarkers or potential therapeutic targets for obesity. The gene expression profile of E-MTAB-6728 was downloaded from the database. After screening DEGs in each ArrayExpress dataset, we further used the robust rank aggregation method to diagnose 876 significant DEGs including 438 up regulated and 438 down regulated genes. Functional enrichment analysis was performed. These DEGs were shown to be significantly enriched in different obesity related pathways and GO functions. Then protein-protein interaction network, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. The module analysis was performed based on the whole PPI network. We finally filtered out STAT3, CORO1C, SERPINH1, MVP, ITGB5, PCM1, SIRT1, EEF1G, PTEN and RPS2 hub genes. Hub genes were validated by ICH analysis, receiver operating curve (ROC) analysis and RT-PCR. Finally a molecular docking study was performed to find small drug molecules. The robust DEGs linked with the development of obesity were screened through the expression profile, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for obesity.

Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the metabolic disorder that appears during pregnancy. The current investigation aimed to identify central differentially expressed genes (DEGs) in GDM. The transcription profiling by array data (E-MTAB-6418) was obtained from the ArrayExpress database. The DEGs between GDM samples and non-GDM samples were analyzed. Functional enrichment analysis were performed using ToppGene. Then we constructed the protein-protein interaction (PPI) network of DEGs by the Search Tool for the Retrieval of Interacting Genes database (STRING) and module analysis was performed. Subsequently, we constructed the miRNA-hub gene network and TF-hub gene regulatory network. The validation of hub genes was performed through receiver operating characteristic curve (ROC). Finally, the candidate small molecules as potential drugs to treat GDM were predicted by using molecular docking. Through transcription profiling by array data, a total of 869 DEGs were detected including 439 up-regulated and 430 down-regulated genes. Functional enrichment analysis showed these DEGs were mainly enriched in reproduction, cell adhesion, cell surface interactions at the vascular wall and extracellular matrix organization. Ten genes, HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3 and PRKCA were associated with GDM, according to ROC analysis. Finally, the most significant small molecules were predicted based on molecular docking. This investigation identified hub genes, signal pathways and therapeutic agents, which might help us, enhance our understanding of the mechanisms of GDM and find some novel therapeutic agents for GDM.

Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules.

BACKGROUND: Obesity associated type 2 diabetes mellitus is a metabolic disorder ; however, the etiology of obesity associated type 2 diabetes mellitus remains largely unknown. There is an urgent need to further broaden the understanding of the molecular mechanism associated in obesity associated type 2 diabetes mellitus. METHODS: To screen the differentially expressed genes (DEGs) that might play essential roles in obesity associated type 2 diabetes mellitus, the publicly available expression profiling by high throughput sequencing data (GSE143319) was downloaded and screened for DEGs. Then, Gene Ontology (GO) and REACTOME pathway enrichment analysis were performed. The protein - protein interaction network, miRNA - target genes regulatory network and TF-target gene regulatory network were constructed and analyzed for identification of hub and target genes. The hub genes were validated by receiver operating characteristic (ROC) curve analysis and RT- PCR analysis. Finally, a molecular docking study was performed on over expressed proteins to predict the target small drug molecules. RESULTS: A total of 820 DEGs were identified between healthy obese and metabolically unhealthy obese, among 409 up regulated and 411 down regulated genes. The GO enrichment analysis results showed that these DEGs were significantly enriched in ion transmembrane transport, intrinsic component of plasma membrane, transferase activity, transferring phosphorus-containing groups, cell adhesion, integral component of plasma membrane and signaling receptor binding, whereas, the REACTOME pathway enrichment analysis results showed that these DEGs were significantly enriched in integration of energy metabolism and extracellular matrix organization. The hub genes CEBPD, TP73, ESR2, TAB1, MAP 3K5, FN1, UBD, RUNX1, PIK3R2 and TNF, which might play an essential role in obesity associated type 2 diabetes mellitus was further screened. CONCLUSIONS: The present study could deepen the understanding of the molecular mechanism of obesity associated type 2 diabetes mellitus, which could be useful in developing therapeutic targets for obesity associated type 2 diabetes mellitus.

Identification of hub genes related to the progression of type 1 diabetes by computational analysis.

BACKGROUND: Type 1 diabetes (T1D) is a serious threat to childhood life and has fairly complicated pathogenesis. Profound attempts have been made to enlighten the pathogenesis, but the molecular mechanisms of T1D are still not well known. METHODS: To identify the candidate genes in the progression of T1D, expression profiling by high throughput sequencing dataset GSE123658 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and gene ontology (GO) and pathway enrichment analyses were performed. The protein-protein interaction network (PPI), modules, target gene - miRNA regulatory network and target gene - TF regulatory network analysis were constructed and analyzed using HIPPIE, miRNet, NetworkAnalyst and Cytoscape. Finally, validation of hub genes was conducted by using ROC (Receiver operating characteristic) curve and RT-PCR analysis. A molecular docking study was performed. RESULTS: A total of 284 DEGs were identified, consisting of 142 up regulated genes and 142 down regulated genes. The gene ontology (GO) and pathways of the DEGs include cell-cell signaling, vesicle fusion, plasma membrane, signaling receptor activity, lipid binding, signaling by GPCR and innate immune system. Four hub genes were identified and biological process analysis revealed that these genes were mainly enriched in cell-cell signaling, cytokine signaling in immune system, signaling by GPCR and innate immune system. ROC curve and RT-PCR analysis showed that EGFR, GRIN2B, GJA1, CAP2, MIF, POLR2A, PRKACA, GABARAP, TLN1 and PXN might be involved in the advancement of T1D. Molecular docking studies showed high docking score. CONCLUSIONS: DEGs and hub genes identified in the present investigation help us understand the molecular mechanisms underlying the advancement of T1D, and provide candidate targets for diagnosis and treatment of T1D.

Identification of potential and novel target genes in pituitary prolactinoma by bioinformatics analysis.

Pituitary prolactinoma is one of the most complicated and fatally pathogenic pituitary adenomas. Therefore, there is an urgent need to improve our understanding of the underlying molecular mechanism that drives the initiation, progression, and metastasis of pituitary prolactinoma. The aim of the present study was to identify the key genes and signaling pathways associated with pituitary prolactinoma using bioinformatics analysis. Transcriptome microarray dataset GSE119063 was downloaded from Gene Expression Omnibus (GEO) database. Limma package in R software was used to screen DEGs. Pathway and Gene ontology (GO) enrichment analysis were conducted to identify the biological role of DEGs. A protein-protein interaction (PPI) network was constructed and analyzed by using HIPPIE database and Cytoscape software. Module analyses was performed. In addition, a target gene-miRNA regulatory network and target gene-TF regulatory network were constructed by using NetworkAnalyst and Cytoscape software. Finally, validation of hub genes by receiver operating characteristic (ROC) curve analysis. A total of 989 DEGs were identified, including 461 up regulated genes and 528 down regulated genes. Pathway enrichment analysis showed that the DEGs were significantly enriched in the retinoate biosynthesis II, signaling pathways regulating pluripotency of stem cells, ALK2 signaling events, vitamin D3 biosynthesis, cell cycle and aurora B signaling. Gene Ontology (GO) enrichment analysis showed that the DEGs were significantly enriched in the sensory organ morphogenesis, extracellular matrix, hormone activity, nuclear division, condensed chromosome and microtubule binding. In the PPI network and modules, SOX2, PRSS45, CLTC, PLK1, B4GALT6, RUNX1 and GTSE1 were considered as hub genes. In the target gene-miRNA regulatory network and target gene-TF regulatory network, LINC00598, SOX4, IRX1 and UNC13A were considered as hub genes. Using integrated bioinformatics analysis, we identified candidate genes in pituitary prolactinoma, which might improve our understanding of the molecular mechanisms of pituitary prolactinoma.

Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules.

To enhance understanding of polycystic ovary syndrome (PCOS) at the molecular level; this investigation intends to examine the genes and pathways associated with PCOS by using an integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing data GSE84958 derived from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) between PCOS samples and normal controls were identified. We performed a functional enrichment analysis. A protein-protein interaction (PPI) network, miRNA- target genes and TF - target gene networks, were constructed and visualized, with which the hub gene nodes were identified. Validation of hub genes was performed by using receiver operating characteristic (ROC) and RT-PCR. Small drug molecules were predicted by using molecular docking. A total of 739 DEGs were identified, of which 360 genes were up regulated and 379 genes were down regulated. GO enrichment analysis revealed that up regulated genes were mainly involved in peptide metabolic process, organelle envelope and RNA binding and the down regulated genes were significantly enriched in plasma membrane bounded cell projection organization, neuron projection and DNA-binding transcription factor activity, RNA polymerase II-specific. REACTOME pathway enrichment analysis revealed that the up regulated genes were mainly enriched in translation and respiratory electron transport and the down regulated genes were mainly enriched in generic transcription pathway and transmembrane transport of small molecules. The top 10 hub genes (SAA1, ADCY6, POLR2K, RPS15, RPS15A, CTNND1, ESR1, NEDD4L, KNTC1 and NGFR) were identified from PPI network, miRNA - target gene network and TF - target gene network. The modules analysis showed that genes in modules were mainly associated with the transport of respiratory electrons and signaling NGF, respectively. We find a series of crucial genes along with the pathways that were most closely related with PCOS initiation and advancement. Our investigations provide a more detailed molecular mechanism for the progression of PCOS, detail information on the potential biomarkers and therapeutic targets.

Potential Molecular Mechanisms and Remdesivir Treatment for Acute Respiratory Syndrome Corona Virus 2 Infection/COVID 19 Through RNA Sequencing and Bioinformatics Analysis.

INTRODUCTION: Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infections (COVID 19) is a progressive viral infection that has been investigated extensively. However, genetic features and molecular pathogenesis underlying remdesivir treatment for SARS-CoV-2 infection remain unclear. Here, we used bioinformatics to investigate the candidate genes associated in the molecular pathogenesis of remdesivir-treated SARS-CoV-2-infected patients. METHODS: Expression profiling by high-throughput sequencing dataset (GSE149273) was downloaded from the Gene Expression Omnibus, and the differentially expressed genes (DEGs) in remdesivir-treated SARS-CoV-2 infection samples and nontreated SARS-CoV-2 infection samples with an adjusted P value of <.05 and a |log fold change| > 1.3 were first identified by limma in R software package. Next, pathway and gene ontology (GO) enrichment analysis of these DEGs was performed. Then, the hub genes were identified by the NetworkAnalyzer plugin and the other bioinformatics approaches including protein-protein interaction network analysis, module analysis, target gene-miRNA regulatory network, and target gene-TF regulatory network. Finally, a receiver-operating characteristic analysis was performed for diagnostic values associated with hub genes. RESULTS: A total of 909 DEGs were identified, including 453 upregulated genes and 457 downregulated genes. As for the pathway and GO enrichment analysis, the upregulated genes were mainly linked with influenza A and defense response, whereas downregulated genes were mainly linked with drug metabolism-cytochrome P450 and reproductive process. In addition, 10 hub genes (VCAM1, IKBKE, STAT1, IL7R, ISG15, E2F1, ZBTB16, TFAP4, ATP6V1B1, and APBB1) were identified. Receiver-operating characteristic analysis showed that hub genes (CIITA, HSPA6, MYD88, SOCS3, TNFRSF10A, ADH1A, CACNA2D2, DUSP9, FMO5, and PDE1A) had good diagnostic values. CONCLUSION: This study provided insights into the molecular mechanism of remdesivir-treated SARS-CoV-2 infection that might be useful in further investigations.

Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods.

The goal of the present investigation is to identify the differentially expressed genes (DEGs) between SARS-CoV-2 infected and normal control samples to investigate the molecular mechanisms of infection with SARS-CoV-2. The microarray data of the dataset E-MTAB-8871 were retrieved from the ArrayExpress database. Pathway and Gene Ontology (GO) enrichment study, protein-protein interaction (PPI) network, modules, target gene-miRNA regulatory network, and target gene-TF regulatory network have been performed. Subsequently, the key genes were validated using an analysis of the receiver operating characteristic (ROC) curve. In SARS-CoV-2 infection, a total of 324 DEGs (76 up- and 248 down-regulated genes) were identified and enriched in a number of associated SARS-CoV-2 infection pathways and GO terms. Hub and target genes such as TP53, HRAS, MAPK11, RELA, IKZF3, IFNAR2, SKI, TNFRSF13C, JAK1, TRAF6, KLRF2, CD1A were identified from PPI network, target gene-miRNA regulatory network, and target gene-TF regulatory network. Study of the ROC showed that ten genes (CCL5, IFNAR2, JAK2, MX1, STAT1, BID, CD55, CD80, HAL-B, and HLA-DMA) were substantially involved in SARS-CoV-2 patients. The present investigation identified key genes and pathways that deepen our understanding of the molecular mechanisms of SARS-CoV-2 infection, and could be used for SARS-CoV-2 infection as diagnostic and therapeutic biomarkers.

Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection is a leading cause of pneumonia and death. The aim of this investigation is to identify the key genes in SARS-CoV-2 infection and uncover their potential functions. We downloaded the expression profiling by high throughput sequencing of GSE152075 from the Gene Expression Omnibus database. Normalization of the data from primary SARS-CoV-2 infected samples and negative control samples in the database was conducted using R software. Then, joint analysis of the data was performed. Pathway and Gene ontology (GO) enrichment analyses were performed, and the protein-protein interaction (PPI) network, target gene - miRNA regulatory network, target gene - TF regulatory network of the differentially expressed genes (DEGs) were constructed using Cytoscape software. Identification of diagnostic biomarkers was conducted using receiver operating characteristic (ROC) curve analysis. 994 DEGs (496 up regulated and 498 down regulated genes) were identified. Pathway and GO enrichment analysis showed up and down regulated genes mainly enriched in the NOD-like receptor signaling pathway, Ribosome, response to external biotic stimulus and viral transcription in SARS-CoV-2 infection. Down and up regulated genes were selected to establish the PPI network, modules, target gene - miRNA regulatory network, target gene - TF regulatory network revealed that these genes were involved in adaptive immune system, fluid shear stress and atherosclerosis, influenza A and protein processing in endoplasmic reticulum. In total, ten genes (CBL, ISG15, NEDD4, PML, REL, CTNNB1, ERBB2, JUN, RPS8 and STUB1) were identified as good diagnostic biomarkers. In conclusion, the identified DEGs, hub genes and target genes contribute to the understanding of the molecular mechanisms underlying the advancement of SARS-CoV-2 infection and they may be used as diagnostic and molecular targets for the treatment of patients with SARS-CoV-2 infection in the future.

Analysis of Differentially Expressed Genes in Coronary Artery Disease by Integrated Microarray Analysis.

Coronary artery disease (CAD) is a major cause of end-stage cardiac disease. Although profound efforts have been made to illuminate the pathogenesis, the molecular mechanisms of CAD remain to be analyzed. To identify the candidate genes in the advancement of CAD, microarray dataset GSE23766 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and pathway and gene ontology (GO) enrichment analyses were performed. The protein-protein interaction network was constructed and the module analysis was performed using the Biological General Repository for Interaction Datasets (BioGRID) and Cytoscape. Additionally, target genes-miRNA regulatory network and target genes-TF regulatory network were constructed and analyzed. There were 894 DEGs between male human CAD samples and female human CAD samples, including 456 up regulated genes and 438 down regulated genes. Pathway enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the superpathway of steroid hormone biosynthesis, ABC transporters, oxidative ethanol degradation III and Complement and coagulation cascades. Similarly, geneontology enrichment analyses revealed that DEGs (up and down regulated) were mostly enriched in the forebrain neuron differentiation, filopodium membrane, platelet degranulation and blood microparticle. In the PPI network and modules (up and down regulated), MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74 and VHL were hub genes. In the target genes-miRNA regulatory network and target genes-TF regulatory network (up and down regulated), TAOK1, KHSRP, HSD17B11 and PAH were target genes. In conclusion, the pathway and GO ontology enriched by DEGs may reveal the molecular mechanism of CAD. Its hub and target genes, MYC, NPM1, TRPC7, UBC, FN1, HEMK1, IFT74, VHL, TAOK1, KHSRP, HSD17B11 and PAH were expected to be new targets for CAD. Our finding provided clues for exploring molecular mechanism and developing new prognostics, diagnostic and therapeutic strategies for CAD.

Identification of important invasion and proliferation related genes in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is an end-stage hormonal syndrome. Although profound attempts have been made to illuminate the pathogenesis, the molecular mechanisms of ACC remain to be clarified. To identify the important genes in the progression of ACC, microarray datasets GSE19775 was downloaded from the gene expression omnibus database. The differentially-expressed genes (DEGs) were identified, and pathway and GO enrichment analyses were performed. The protein-protein interaction (PPI) network was constructed and the module analysis was performed using the protein interaction network analysis and Cytoscape. Also constructed target genes-miRNA regulatory network and target genes-TF regulatory network. Correlation of the hub genes were analyzed in The Cancer Genome Atlas. The prognostic values of hub genes were further validated by online tool UALCAN. Mutation analysis was done by online tool CBio Cancer Genomics Portal. A total of 884 DEGs were identified, with 441 in up regulation and 443 in down regulation. Pathways in catecholamine biosynthesis, aldosterone synthesis and secretion, pyrimidine deoxyribonucleosides salvage and systemic lupus erythematosus were the most significantly enriched for DEGs (up and down regulated). Blood vessel morphogenesis and cell cycle phase transition were the most significantly enriched term in biological processes, while extracellular matrix and chromosome, centromeric region were in cellular component and heparin binding and protein dimerization activity were in molecular function. Among the PPI networks and its module, target genes-miRNA regulatory network and target genes-TF regulatory network, hub genes were YWHAZ, FN1, GRK5, VCAM1, GATA6, TXNIP, HSPA1A, and F11R. Hub genes such as YWHAZ, STAT1, ICAM1, SH3BP5, CD83, FN1, TK1, HIST1H1C, CABLES1, and MCM3 were associated with poor overall survival, while hub genes such as STAT1, ICAM1, CD83, FN1, TK1, HIST1H1C, and MCM3 were highly expressed in stage 4. In conclusion, DEGs and hub genes diagnosed in this study may deepen our understanding of molecular mechanisms underlying the progression of ACC, and provide important targets for diagnosis and treatment of ACC.

Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray.

: Breast cancer (BRCA) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers expressed during estradiol and tamoxifen treatment of BRCA. The microarray dataset of E-MTAB-4975 from Array Express database was downloaded, and the differential expressed genes (DEGs) between estradiol-treated BRCA sample and tamoxifen-treated BRCA sample were identified by limma package. The pathway and gene ontology (GO) enrichment analysis, construction of protein-protein interaction (PPI) network, module analysis, construction of target genes-miRNA interaction network and target genes-transcription factor (TF) interaction network were performed using bioinformatics tools. The expression, prognostic values, and mutation of hub genes were validated by SurvExpress database, cBioPortal, and human protein atlas (HPA) database. A total of 856 genes (421 up-regulated genes and 435 down-regulated genes) were identified in T47D (overexpressing Split Ends (SPEN) + estradiol) samples compared to T47D (overexpressing Split Ends (SPEN) + tamoxifen) samples. Pathway and GO enrichment analysis revealed that the DEGs were mainly enriched in response to lysine degradation II (pipecolate pathway), cholesterol biosynthesis pathway, cell cycle pathway, and response to cytokine pathway. DEGs (MCM2, TCF4, OLR1, HSPA5, MAP1LC3B, SQSTM1, NEU1, HIST1H1B, RAD51, RFC3, MCM10, ISG15, TNFRSF10B, GBP2, IGFBP5, SOD2, DHF and MT1H) , which were significantly up- and down-regulated in estradiol and tamoxifen-treated BRCA samples, were selected as hub genes according to the results of protein-protein interaction (PPI) network, module analysis, target genes-miRNA interaction network and target genes-TF interaction network analysis. The SurvExpress database, cBioPortal, and Human Protein Atlas (HPA) database further confirmed that patients with higher expression levels of these hub genes experienced a shorter overall survival. A comprehensive bioinformatics analysis was performed, and potential therapeutic applications of estradiol and tamoxifen were predicted in BRCA samples. The data may unravel the future molecular mechanisms of BRCA.