Identification of the key differentially expressed genes and pathways involved in neutrophilia

Polymorphonuclear neutrophils (PMNs) are the most important determinants in the acute inflammatory response. Pathologically increased numbers of PMNs in the circulation or specific tissues (or both) lead to neutrophilia. However, the genes expressed and pathways involved in neutrophilia have yet to be elucidated. By analysis of three public microarray datasets related to neutrophilia (GSE64457, GSE54644, and GSE94923) and evaluation by gene ontology, pathway enrichment, protein–protein interaction networks, and hub genes analysis using multiple methods (DAVID, PATHER, Reactome, STRING, Reactome FI Plugin, and CytoHubba in Cytoscape), we identified the commonly up-regulated and down-regulated different expressed genes. We also discovered that multiple signaling pathways (IL-mediated, LPS-mediated, TNF-α, TLR cascades, MAPK, and PI3K-Akt) were involved in PMN regulation. Our findings suggest that the commonly expressed genes involved in regulation of multiple pathways were the underlying molecular mechanisms in the development of inflammatory, autoimmune, and hematologic diseases that share the common phenotypic characteristics of increased numbers of PMNs. Taken together, these data suggest that these genes are involved in the regulation of neutrophilia and that the corresponding gene products could serve as potential biomarkers and/or therapeutic targets for neutrophilia.

Download Full-text

Comprehensive Analysis of Common Different Gene Expression Signatures in the Neutrophils of Sepsis

BioMed Research International ◽

10.1155/2021/6655425 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Zhaojun Liu ◽

Yang Chen ◽

Tingting Pan ◽

Jialin Liu ◽

Rui Tian ◽

...

Keyword(s):

Immune System ◽

Molecular Mechanisms ◽

Clinical Samples ◽

Central Component ◽

Inflammatory Disorder ◽

Rt Pcr ◽

Hub Gene ◽

Pathway Enrichment ◽

Protein Protein Interaction ◽

Pathogenic Factors

The central component of sepsis pathogenesis is inflammatory disorder, which is related to dysfunction of the immune system. However, the specific molecular mechanism of sepsis has not yet been fully elucidated. The aim of our study was to identify genes that are significantly changed during sepsis development, for the identification of potential pathogenic factors. Differentially expressed genes (DEGs) were identified in 88 control and 214 septic patient samples. Gene ontology (GO) and pathway enrichment analyses were performed using David. A protein-protein interaction (PPI) network was established using STRING and Cytoscape. Further validation was performed using real-time polymerase chain reaction (RT-PCR). We identified 37 common DEGs. GO and pathway enrichment indicated that enzymes and transcription factors accounted for a large proportion of DEGs; immune system and inflammation signaling demonstrated the most significant changes. Furthermore, eight hub genes were identified via PPI analysis. Interestingly, four of the top five upregulated and all downregulated DEGs were involved in immune and inflammation signaling. In addition, the most intensive hub gene AKT1 and the top DEGs in human clinical samples were validated using RT-PCR. This study explored the possible molecular mechanisms underpinning the inflammatory, immune, and PI3K/AKT pathways related to sepsis development.

Download Full-text

Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis

10.20944/preprints201812.0018.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Md. Rezanur Rahman ◽

Tania Islam ◽

Esra Gov ◽

Beste Turanli ◽

Md. Shahjaman ◽

...

Keyword(s):

Colorectal Cancer ◽

Drug Repositioning ◽

Molecular Biomarker ◽

Cell Cycles ◽

Pathway Enrichment ◽

Protein Protein Interaction ◽

Network Analyses ◽

Microarray Datasets ◽

Prognostic Power ◽

Hub Proteins

Background and objectives: Colorectal cancer (CRC) is the 2nd most cause of cancer related death in the world, but early diagnosis ameliorates the survival of CRC. This report directed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed two microarray datasets (GSE35279 and GSE21815) to identify common differentially expressed genes (DEGs). We performed functional overrepresentation, pathway enrichment, protein-protein interaction (PPI), reporter biomolecules, survival, and drug repositioning analyses were done on common DEGs. Results: Total 727 up-regulated and 99 down-regulated DEGs were detected. The significantly enriched pathways PI3K-Akt signaling, Wnt signaling, ECM-interaction, cell cycles were identified. The 10 hub proteins (ADNP, CCND1, CD44, CDK4, CEBPB, CENPA, CENPH, CENPN, MYC, and RFC2) were selected as proteomic signatures from PPI network. Analyses revealed 10 reporter transcription factors (ETS1, ESR1, GATA1, GATA2, GATA3, AR, YBX1, FOXP3, E2F4, and PRDM14) and 2 reporter microRNAs (miR-193b-3p and miR-615-3p) as regulatory component. The prognostic power analysis revealed that hub proteins and reporter biomolecules related with worse survival of patients in CRC. Several candidate repositioned drugs including anti-neoplastic and immunomodulating agents were identified using Connectivity map (CMap) and geneXpharma tool. Conclusions: This study presents biomarker signatures at protein and RNA levels with prognostic capability in CRC. We think that the molecular signatures and candidate drugs presented in this study can be potential biomarkers and therapeutic target in CRC.

Download Full-text

Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

10.1101/2020.07.17.208397 ◽

2020 ◽

Author(s):

Xiaoqin Wang ◽

Ming Chen ◽

Liuzhi Zeng ◽

Longqian Liu

Keyword(s):

Gene Expression ◽

Aqueous Humor ◽

Molecular Mechanisms ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Gene Expression Omnibus ◽

Open Angle ◽

Pathway Enrichment ◽

Protein Protein Interaction ◽

Non Coding Rnas

AbstractPrimary open-angle glaucoma (POAG) is the leading cause of blindness globally, which develops through complex and poorly understood biological mechanisms. Herein, we conducted an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and regulatory mechanisms governing POAG progression. We downloaded AH gene expression datasets (GSE101727 and GSE105269) corresponding to healthy controls and POAG patients from the Gene Expression Omnibus. We then identified mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were differentially expressed (DE) between control and POAG patients. DEmRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein-protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA-miRNA-mRNA and miRNA-transcription factor(TF)-mRNA networks. In total, the GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 37, 5, and 14 of these lncRNAs, miRNAs and mRNAs, respectively. The proteins encoded by these 14 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA-TF-mRNA regulatory network containing 2 miRNAs (miR-135a-5p and miR-139-5p), 5 TFs (TGIF2, TBX5, HNF1A, TCF3, and FOS) and 5 mRNAs (SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2). The SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2 genes that may be viable therapeutic targets for the prevention or treatment of POAG, and regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

Download Full-text

Weighted gene co-expression network analysis to identify key modules and hub genes related to hyperlipidaemia

10.21203/rs.3.rs-54056/v2 ◽

2021 ◽

Author(s):

Fu Jun Liao ◽

Peng-Fei Zheng ◽

Yao-Zong Guan ◽

Hong Wei Pan ◽

Wei Li

Keyword(s):

Molecular Mechanisms ◽

Acid Metabolism ◽

Unsaturated Fatty Acids ◽

Microarray Dataset ◽

Hub Genes ◽

Online Tool ◽

Pathway Enrichment ◽

Protein Protein Interaction ◽

Qpcr Analysis ◽

Blue Module

Abstract Background: The purpose of this study was to explore the potential molecular targets of hyperlipidaemia and the related molecular mechanisms.Methods: The microarray dataset of GSE66676 obtained from patients with hyperlipidaemia was downloaded. Weighted gene co-expression network (WGCNA) analysis was used to analyse the gene expression profile, and the royal blue module was considered to have the highest correlation. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were implemented for the identification of genes in the royal blue module using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool (version 6.8; http://david.abcc.ncifcrf.gov). A protein-protein interaction (PPI) network was established by using the online STRING tool. Then, several hub genes were identified by the MCODE and cytoHubba plug-ins in Cytoscape software.Results: The significant module (royal blue) identified was associated with TC, TG and non-HDL-C. GO and KEGG enrichment analyses revealed that the genes in the royal blue module were associated with carbon metabolism, steroid biosynthesis, fatty acid metabolism and biosynthesis pathways of unsaturated fatty acids. SQLE (degree = 17) was revealed as a key molecule associated with hypercholesterolaemia (HCH), and SCD was revealed as a key molecule associated with hypertriglyceridaemia (HTG). RT-qPCR analysis also confirmed the above results based on our HCH/HTG samples.Conclusions: SQLE and SCD are related to hyperlipidaemia, and SQLE/SCD may be new targets for cholesterol-lowering or triglyceride-lowering therapy, respectively.

Download Full-text

Weighted gene co-expression network analysis to identify key modules and hub genes related to hyperlipidaemia

10.21203/rs.3.rs-54056/v1 ◽

2020 ◽

Author(s):

Fu Jun Liao ◽

Peng-Fei Zheng ◽

Yao-Zong Guan ◽

Wei Li

Keyword(s):

Molecular Mechanisms ◽

Acid Metabolism ◽

Unsaturated Fatty Acids ◽

Kegg Pathway ◽

Hub Genes ◽

Data Set ◽

Online Tool ◽

Pathway Enrichment ◽

Protein Protein Interaction ◽

Qpcr Analysis

Abstract Background: The purpose of this study was to explore the potential molecular targets of hyperlipidaemia and the related molecular mechanisms.Methods: The microarray data set of GSE66676 obtained from patients with hyperlipidaemia was downloaded. The weighted gene co‑expression network (WGCNA) analysis was used to analyze the gene expression profile and royalblue module was considered as the highest correlation. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and genomes (KEGG) pathway enrichment analyses were implemented for the identification of genes in the royalblue module using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool (version 6.8; http://david.abcc.ncifcrf.gov). A protein-protein interaction (PPI) network was established by using the online STRING tool. Then, several hub genes were identified by the MCODE and cytoHubba plug-ins in Cytoscape software.Results: The significant module (royalblue) identified was associated with TC, TG and Non-HDL-C. GO and KEGG enrichment analyses revealed that the genes in the royalblue module were associated with carbon metabolism, steroid biosynthesis, fatty acid metabolism and biosynthesis of unsaturated fatty acids pathways. SQLE (degree = 17) was revealed as key molecules that associated with hypercholesterolemia (HCH) and SCD was revealed as key molecules that associated with hypertriglyceridemia (HTG). Meanwhile, RT-qPCR analysis also confirmed the above results based on our HCH/HTG samples.Conclusions: SQLE and SCD are related to hyperlipidaemia, SQLE/SCD may be new targets for cholesterol-lowering or triglyceride-lowering therapy, respectively.

Download Full-text

Distinct Expression of miR-378 in Nonsyndromic Cleft Lip and/or Cleft Palate: A Cogitation of Skewed Sex Ratio in Prevalence

The Cleft Palate-Craniofacial Journal ◽

10.1177/1055665620935364 ◽

2020 ◽

Vol 58 (1) ◽

pp. 61-71

Author(s):

Yuzi Xu ◽

Binbin Xie ◽

Jue Shi ◽

Jia Li ◽

Chuan Zhou ◽

...

Keyword(s):

Sex Ratio ◽

Cleft Palate ◽

Messenger Rna ◽

Regulatory Networks ◽

Cleft Lip ◽

Bioinformatics Analysis ◽

Gene Expression Omnibus ◽

Pathway Enrichment ◽

Protein Protein Interaction ◽

Protein Protein Interaction Networks

Objective: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) is an isolated phenotype of orofacial clefts with skewed sex ratio in prevalence. This study aims to identify differentially expressed genes (DEGs) and microRNAs (DEMs) of NSCL/P by integrated bioinformatics analysis, revealing mechanisms for sexual dimorphism in prevalence. Materials and Methods: First, we downloaded the expression profile data from Gene Expression Omnibus database to identify DEGs and DEMs. Second, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses performed DEGs’ functions. Then, clustered DEGs were identified through protein–protein interaction networks. Combining clustered DEGs with key genes searched in GeneCards enlarged NSCL/P-related genes. Moreover, the genes were linked by transcription factors (TFs). Subsequently, connected by the above TFs, DEMs and genes were used to establish the miRNA-TF-messenger RNA (mRNA) regulatory networks. Results: The DEGs in sex-ignored group, female-only group, and male-only group were obtained, respectively. Among the DEMs, miR-378 was downregulated in females but upregulated in males. In female-only group, the miRNA-TF-mRNA regulatory networks showed miR-378-SP1-POLE2/CDK6/EZR regulatory axis was found to be key candidates of NSCL/P. Conclusions: Our findings suggest that different expression of miR-378 is consistent with the skewed sex ratio in the prevalence of NSCL/P.

Download Full-text

ACE2 Protein-Protein Interaction Networks Reveal Potential Druggable Targets For SARS-CoV-2

10.21203/rs.3.rs-54096/v2 ◽

2021 ◽

Author(s):

Qiaoxi Xia ◽

Xiao Zhou ◽

Mantong Chen ◽

Ling Lin ◽

Yan Zhao ◽

...

Keyword(s):

Protein Interaction ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Biological Response ◽

Protein Interaction Networks ◽

Interaction Networks ◽

Host Cells ◽

Interacting Proteins ◽

Protein Protein Interaction ◽

Protein Protein Interaction Networks

Abstract Background: The novel coronavirus SARS-CoV-2 pandemic has infected more than 130 million people, killed over 2.3 million so far. Currently, no effective drugs are available to treat this infectious disease, due to limited knowledge of the molecular mechanisms of SARS-CoV-2 infection. ACE2 (angiotensin I converting enzyme 2) has long been identified as the major receptor for coronavirus entry the host cells. Methods: In this study, we constructed the protein-protein interaction networks (PPIN) based on ACE2 and its interacting proteins, considering with the expression alternation and co-expression relationship. The potential drugs targeting the proteins in the PPIN were explored.Results: ACE2 and its interacting proteins AAMP and HRAS are obviously increased, and their PPIN show distinguishing expression patterns during the COVID-19 progression. At least six pathways are activated for the host cell in the response to the virus. Moreover, drug-target networks were built to provide important clues to block ACE2 and its interacting proteins. Except the reported four drugs for ACE2, its interacting protein CALM1 and HRAS are great potentially druggable. We also considered the path initiated from ACE2 to nucleus by cascades of interaction, especially for the transcription factors in the PPIN which are also druggable.Conclusion: In summary, this study provides new insight into the disruption of the biological response to virus mediated by ACE2, but also its cascade interacting proteins when considering of PPIN.

Download Full-text

Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme

Journal of International Medical Research ◽

10.1177/0300060520924541 ◽

2020 ◽

Vol 48 (7) ◽

pp. 030006052092454

Author(s):

Fuwei Qi ◽

Qing Li ◽

Xiaojun Lu ◽

Zhihua Chen

Keyword(s):

Gene Expression ◽

Glioblastoma Multiforme ◽

Molecular Mechanisms ◽

Interaction Network ◽

Gene Expression Omnibus ◽

Protein Protein Interaction ◽

Diagnosis And Prognosis ◽

Novel Biomarkers ◽

Patient Prognosis ◽

Microarray Datasets

Objective There have been no recent improvements in the glioblastoma multiforme (GBM) outcome, with median survival remaining 15 months. Consequently, the need to identify novel biomarkers for GBM diagnosis and prognosis, and to develop targeted therapies is high. This study aimed to establish biomarkers for GBM pathogenesis and prognosis. Methods In total, 220 overlapping differentially expressed genes (DEGs) were obtained by integrating four microarray datasets from the Gene Expression Omnibus database (GSE4290, GSE12657, GSE15824, and GSE68848). Then a 140-node protein–protein interaction network with 343 interactions was constructed. Results The immune response and cell adhesion molecules were the most significantly enriched functions and pathways, respectively, among DEGs. The designated hub genes ITGB5 and RGS4, which have a high degree of connectivity, were closely correlated with patient prognosis, and GEPIA database mining further confirmed their differential expression in GBM versus normal tissue. We also determined the 20 most appropriate small molecules that could potentially reverse GBM gene expression, Prestwick-1080 was the most promising and had the highest negative scores. Conclusions This study identified ITGB5 and RGS4 as potential biomarkers for GBM diagnosis and prognosis. Insights into molecular mechanisms governing GBM occurrence and progression will help identify alternative biomarkers for clinical practice.

Download Full-text

Transcriptome Profiling Based on Different Time Points After Hatching Provides a Core Set of Gene Resource for Understanding Larval Immune Response Mechanisms Against Vibrio anguillarum Infection in Amphioctopus fangsiao

Frontiers in Marine Science ◽

10.3389/fmars.2021.731517 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaokai Bao ◽

Yan Li ◽

Jianbai Zhang ◽

Xipan Chen ◽

Xiaohui Xu ◽

...

Keyword(s):

Immune Response ◽

Protein Interaction ◽

Molecular Mechanisms ◽

Vibrio Anguillarum ◽

Immune Defense ◽

Protein Interaction Networks ◽

Interaction Networks ◽

Time Points ◽

Protein Protein Interaction ◽

Protein Protein Interaction Networks

Immune defense systems are indispensable for living organisms. Within an immune network, problems with any given link can impact the normal life activities of an organism. Amphioctopus fangsiao is a cephalopod that exists widely throughout the world’s oceans. Because of its nervous system and locomotive organs, it has become increasingly studied in recent years. Vibrio anguillarum is one of the most common pathogenic bacteria in aquaculture organisms. It is highly infectious and can infect almost all aquaculture organisms. V. anguillarum infection can cause many adverse biological phenomena, including tissue bleeding. Study the immune response after V. anguillarum infection would help us to understand the molecular mechanisms of immune response in aquaculture organisms. In this research, we infected the primary incubation A. fangsiao with V. anguillarum for 24 h. We analyzed gene expression in A. fangsiao larvae via transcriptome profiles at 0, 4, 12, and 24 h after hatching, and 1,385, 734, and 6,109 differentially expressed genes (DEGs) were identified at these three time points. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify immune-related DEGs. Protein–protein interaction networks were constructed to examine interactions between immune-related genes. Twenty hub genes involved in multiple KEGG signaling pathways or with multiple protein–protein interaction relationships were identified, and their differential expression verified by quantitative RT-PCR. We first studied V. anguillarum infection of A. fangsiao larvae by means of protein–protein interaction networks. The results provide valuable genetic resources for understanding immunity in molluscan larvae. These data serve as a theoretical basis for the artificial breeding of A. fangsiao.

Download Full-text

Unraveling the Molecular Mechanisms of Fructus Anisi Stellati as a Remedy for Infantile Colic by Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9210304 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Xingyu Li ◽

Yan Xu

Keyword(s):

Molecular Mechanisms ◽

Immunoglobulin A ◽

Chemical Compounds ◽

Network Pharmacology ◽

Infantile Colic ◽

Inflammatory Reactions ◽

Pathway Enrichment ◽

The Common ◽

Iga Production ◽

Therapeutic Compounds

Fructus anisi stellati (FAS) is an anise-scented star-shaped fruit from Illicium verum tree. It is commonly consumed in many cultures as food and medicine, particularly as a remedy for infantile colic (IC). The elucidation of molecular mechanisms of action would contribute to the understanding of the traditional therapy of FAS and help to guide the preclinical and clinical study of this herb. The aim is to investigate the key therapeutic compounds of FAS and to explore the underlying molecular mechanisms of FAS therapy. The chemical compounds of FAS were obtained through data mining on TCMSP and ADME screening, and the common targets of the FAS compounds and the IC-correlated diseases were obtained from PharmMapper, GeneCards, and OMIM databases. GO and KEGG databases were used for molecular function and pathway enrichment. Cytoscape was used for network construction and analysis. SystemsDock was used for molecular docking. Three key compounds (i.e., quercetin, luteolin, and kaempferol), 19 targets, 7 molecular pathways, and 12 IC-correlated diseases were identified to be involved in the molecular mechanisms of FAS for the treatment of IC. This work showed that three therapeutic modules were primarily engaged in the molecular mechanisms of FAS for IC therapy, including the inhibition of inflammatory reactions, stimulating immunoglobulin A (IgA) production in the gastrointestinal tract, and enhancing the secretion of digestive enzymes.

Download Full-text