Consistent Biomarkers and Related Pathogenesis Underlying Asthma Revealed by Systems Biology Approach

Asthma is a common chronic airway disease worldwide. Due to its clinical and genetic heterogeneity, the cellular and molecular processes in asthma are highly complex and relatively unknown. To discover novel biomarkers and the molecular mechanisms underlying asthma, several studies have been conducted by focusing on gene expression patterns in epithelium through microarray analysis. However, few robust specific biomarkers were identified and some inconsistent results were observed. Therefore, it is imperative to conduct a robust analysis to solve these problems. Herein, an integrated gene expression analysis of ten independent, publicly available microarray data of bronchial epithelial cells from 348 asthmatic patients and 208 healthy controls was performed. As a result, 78 up- and 75 down-regulated genes were identified in bronchial epithelium of asthmatics. Comprehensive functional enrichment and pathway analysis revealed that response to chemical stimulus, extracellular region, pathways in cancer, and arachidonic acid metabolism were the four most significantly enriched terms. In the protein-protein interaction network, three main communities associated with cytoskeleton, response to lipid, and regulation of response to stimulus were established, and the most highly ranked 6 hub genes (up-regulated CD44, KRT6A, CEACAM5, SERPINB2, and down-regulated LTF and MUC5B) were identified and should be considered as new biomarkers. Pathway cross-talk analysis highlights that signaling pathways mediated by IL-4/13 and transcription factor HIF-1α and FOXA1 play crucial roles in the pathogenesis of asthma. Interestingly, three chemicals, polyphenol catechin, antibiotic lomefloxacin, and natural alkaloid boldine, were predicted and may be potential drugs for asthma treatment. Taken together, our findings shed new light on the common molecular pathogenesis mechanisms of asthma and provide theoretical support for further clinical therapeutic studies.

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Regulatory T Cell-Related Gene Biomarkers in the Deterioration of Atherosclerosis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.661709 ◽

2021 ◽

Vol 8 ◽

Author(s):

Meng Xia ◽

Qingmeng Wu ◽

Pengfei Chen ◽

Cheng Qian

Keyword(s):

Gene Expression ◽

Cardiovascular Events ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Expression Patterns ◽

Interaction Network ◽

Gene Signature ◽

Smooth Muscle Contraction ◽

Gene Expression Omnibus ◽

Scoring Method

Background: Regulatory T cells (Tregs) have shown to be protective against the development of atherosclerosis, a major pathological cause for cardiovascular events. Here, we aim to explore the roles of Tregs-related genes in atherosclerosis deterioration.Methods and Results: We downloaded the gene expression profile of 29 atherosclerotic samples from the Gene Expression Omnibus database with an accession number of GSE28829. The abundance of Tregs estimated by the CIBERSORT algorithm was negatively correlated with the atherosclerotic stage. Using the limma test and correlation analysis, a total of 159 differentially expressed Tregs-related genes (DETregRGs) between early and advanced atherosclerotic plaques were documented. Functional annotation analysis using the DAVID tool indicated that the DETregRGs were mainly enriched in inflammatory responses, immune-related mechanisms, and pathways such as complement and coagulation cascades, platelet activation, leukocyte trans-endothelial migration, vascular smooth muscle contraction, and so on. A protein-protein interaction network of the DETregRGs was then constructed, and five hub genes (PTPRC, C3AR1, CD53, TLR2, and CCR1) were derived from the network with node degrees ≥20. The expression patterns of these hub DETregRGs were further validated in several independent datasets. Finally, a single sample scoring method was used to build a gene signature for the five DETregRGs, which could distinguish patients with myocardial infarction from those with stable coronary disease.Conclusion: The results of this study will improve our understanding about the Tregs-associated molecular mechanisms in the progression of atherosclerosis and facilitate the discovery of novel biomarkers for acute cardiovascular events.

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Gene expression profiling in inflammatory airway disease associated with elevated adenosine

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00243.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. L169-L182 ◽

Cited By ~ 20

Author(s):

Suman K. Banerjee ◽

Hays W. J. Young ◽

Jonathan B. Volmer ◽

Michael R. Blackburn

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Cdna Array ◽

Airway Disease ◽

Lung Damage ◽

In Vivo Model ◽

Mouse Cdna ◽

Deficient Mice

Adenosine has been implicated as a modulator of inflammatory processes central to asthma. However, the molecular mechanisms involved are poorly understood. We used Atlas mouse cDNA arrays to analyze differential gene expression in association with lung inflammation resulting from elevated adenosine in adenosine deaminase (ADA)-deficient mice. We report that of the 1,176 genes on the array, the expression patterns of 280 genes were consistently altered. Of these genes, the steady-state levels of 93 genes were upregulated and 29 were downregulated. We also show that lowering adenosine levels with ADA enzyme therapy has striking effects on gene expression that may be associated with resolution of pulmonary eosinophilia. In addition, we confirmed the nucleic acid and protein expression of vascular endothelial growth factor and monocyte chemoattractant protein-3, two candidate genes that may be regulated by adenosine. In conclusion, high-throughput profiling of gene expression by cDNA array hybridization has provided an overview of critical regulatory genes involved in airway inflammation in ADA-deficient mice. These mice will serve as a useful in vivo model for characterizing molecular mechanisms of adenosine-mediated lung damage.

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Screening and identification of key candidate genes and pathways in myelodysplastic syndrome by bioinformatic analysis

PeerJ ◽

10.7717/peerj.8162 ◽

2019 ◽

Vol 7 ◽

pp. e8162

Author(s):

Ying Le

Keyword(s):

Gene Expression ◽

Myelodysplastic Syndrome ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Hematologic Malignancy ◽

Expression Profiles ◽

Interaction Network ◽

Functional Enrichment ◽

Hematopoietic Stem ◽

Diagnosis And Prognosis

Myelodysplastic syndrome (MDS) is a heterogeneous hematologic malignancy derived from hematopoietic stem cells and the molecular mechanism of MDS remains unclear. This study aimed to elucidate potential markers of diagnosis and prognosis of MDS. The gene expression profiles GSE19429 and GSE58831 were obtained and downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in MDS were screened using GEO2R and overlapped DEGs were obtained with Venn Diagrams. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analyses, protein–protein interaction network establishment and survival analyses were performed. Functional enrichment analysis indicated that these DEGs were significantly enriched in the interferon signaling pathway, immune response, hematopoietic cell lineage and the FOXO signaling pathway. Four hub genes and four significant modules including 25 module genes were obtained via Cytoscape MCODE. Survival analysis showed that the overall survival of MDS patients having BLNK, IRF4, IFITM1, IFIT1, ISG20, IFI44L alterations were worse than that without alterations. In conclusion, the identification of these genes and pathways helps understand the underlying molecular mechanisms of MDS and provides candidate targets for the diagnosis and prognosis of MDS.

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Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach

BMC Gastroenterology ◽

10.1186/s12876-021-01626-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhongyuan Lin ◽

Yimin Wang ◽

Shiqing Lin ◽

Decheng Liu ◽

Guohui Mo ◽

...

Keyword(s):

Gene Expression ◽

Irritable Bowel Syndrome ◽

Abdominal Pain ◽

Gastrointestinal Disease ◽

Rectal Mucosa ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Irritable Bowel ◽

Potential Biomarkers

Abstract Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS. Methods Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database. Fifty-three rectal mucosa samples from 27 irritable bowel syndrome with diarrhea (IBS-D) patients and 40 samples from 21 healthy volunteers as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein–protein interaction network was constructed and visualized using STRING database and Cytoscape. Results The microarray analysis demonstrated a subset of genes (CCKBR, CCL13, ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients. Conclusions Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.

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Detoxification and Immune Transcriptomic Response of the Gill Tissue of Bay Scallop (Argopecten irradians) Following Exposure to the Algicide Palmitoleic Acid

Biomolecules ◽

10.3390/biom8040139 ◽

2018 ◽

Vol 8 (4) ◽

pp. 139 ◽

Cited By ~ 3

Author(s):

Cheng Chi ◽

Sib Giri ◽

Jin Jun ◽

Hyoun Kim ◽

Sang Kim ◽

...

Keyword(s):

Gene Expression ◽

Cytochrome P450 ◽

Palmitoleic Acid ◽

Molecular Mechanisms ◽

Functional Enrichment ◽

Alexandrium Tamarense ◽

Read Length ◽

Related Factor ◽

Transcriptomic Response ◽

Bay Scallop

Palmitoleic acid (PA) is an effective algicide against Alexandrium tamarense. However, the toxicological mechanism of PA exposure is unclear. The transcript abundance and differentially expressed genes (DEGs) in gills of bay scallop were investigated following 80 mg/L PA exposure up to 48 h using the Illumina HiSeq 4000 deep-sequencing platform with the recommended read length of 100 bp. De novo assembly of paired-end reads yielded 62,099 unigenes; 5414 genes were identified as being significantly increased, and 4452 were decreased. Based on gene ontology classification and enrichment analysis, the ‘cellular process’, ‘metabolic process’, ‘response to stimulus’, and ‘catalytic process’ with particularly high functional enrichment were revealed. The DEGs, which are related to detoxification and immune responses, revealed that acid phosphatase, fibrinogen C domain-containing protein, cyclic AMP-responsive element-binding protein, glutathione reductase, ATP-binding cassette, nuclear factor erythroid 2-related factor, NADPH2:quinone reductase, and cytochrome P450 4F22, 4B1, and 2C8-related gene expression decreased. In contrast, some genes related to glutathione S-transferase, C-type lectin, superoxide dismutase, toll-like receptors, and cytochrome P450 2C14, 2U1, 3A24 and 4A2 increased. The results of current research will be a valuable resource for the investigation of gene expression stimulated by PA, and will help understanding of the molecular mechanisms underlying the scallops’ response to PA exposure.

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Colon Cancer and SARS-CoV-2: Impact of ACE2 Expression in Susceptibility to COVID-19

10.1101/2020.06.11.146878 ◽

2020 ◽

Cited By ~ 1

Author(s):

Mohsen Ahmadi ◽

Negin Saffarzadeh ◽

Mohammad Amin Habibi ◽

Fatemeh Hajiesmaeili ◽

Nima Rezaei

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Immune Cell ◽

Expression Patterns ◽

Methylation Status ◽

Functional Enrichment ◽

Cell Infiltration ◽

Survival Outcomes ◽

Immune Cell Infiltration ◽

Ace2 Gene

AbstractNovel coronavirus disease (COVID-19) pandemic has become a global health emergency. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) to enter the cells and infects diverse human tissues. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigation of ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. Surprisingly, this methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption, Sulfur relay system, and Fat digestion and absorption pathways. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes of patients with colon cancer by the way of immune cell infiltration linked process. The present study highlights the importance of preventive actions for COAD patients during the COVID-19 pandemic.

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Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children

Frontiers in Immunology ◽

10.3389/fimmu.2021.704633 ◽

2021 ◽

Vol 12 ◽

Author(s):

Piia Karisola ◽

Kati Palosuo ◽

Victoria Hinkkanen ◽

Lukas Wisgrill ◽

Terhi Savinko ◽

...

Keyword(s):

Gene Expression ◽

Clinical Outcome ◽

Immune Responses ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Oral Immunotherapy ◽

Innate Immune ◽

Egg Allergy ◽

Innate Immune Responses ◽

Open Label

We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.

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Multimodal bioinformatic analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

Journal of Medical Genetics ◽

10.1136/jmedgenet-2021-108193 ◽

2021 ◽

pp. jmedgenet-2021-108193

Author(s):

Ido Shalev ◽

Judith Somekh ◽

Alal Eran

Keyword(s):

Protein Interactions ◽

Large Scale ◽

Molecular Mechanisms ◽

Neurological Diseases ◽

Treatment Options ◽

Expression Patterns ◽

Population Variation ◽

Functional Enrichment ◽

Phylogenetic Profiling ◽

Developing Neurons

BackgroundLoss of tectonin β-propeller repeat-containing 2 (TECPR2) function has been implicated in an array of neurodegenerative disorders, yet its physiological function remains largely unknown. Understanding TECPR2 function is essential for developing much needed precision therapeutics for TECPR2-related diseases.MethodsWe leveraged considerable amounts of functional data to obtain a comprehensive perspective of the role of TECPR2 in health and disease. We integrated expression patterns, population variation, phylogenetic profiling, protein-protein interactions and regulatory network data for a minimally biased multimodal functional analysis. Genes and proteins linked to TECPR2 via multiple lines of evidence were subject to functional enrichment analyses to identify molecular mechanisms involving TECPR2.ResultsTECPR2 was found to be part of a tight neurodevelopmental gene expression programme that includes KIF1A, ATXN1, TOM1L2 and FA2H, all implicated in neurological diseases. Functional enrichment analyses of TECPR2-related genes converged on a role in late autophagy and ribosomal processes. Large-scale population variation data demonstrated that this role is non-redundant.ConclusionsTECPR2 might serve as an indicator for the energy balance between protein synthesis and autophagy, and a marker for diseases associated with their imbalance, such as Alzheimer’s disease and Huntington’s disease. Specifically, we speculate that TECPR2 plays an important role as a proteostasis regulator during synaptogenesis, highlighting its importance in developing neurons. By advancing our understanding of TECPR2 function, this work provides an essential stepping stone towards the development of precision diagnostics and targeted treatment options for TECPR2-related disorders.

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Integrative functional analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

10.21203/rs.2.22274/v1 ◽

2020 ◽

Author(s):

Ido Shalev ◽

Judith Somekh ◽

Alal Eran

Keyword(s):

Protein Interactions ◽

Large Scale ◽

Molecular Mechanisms ◽

Neurological Diseases ◽

Treatment Options ◽

Expression Patterns ◽

Population Variation ◽

Functional Enrichment ◽

Phylogenetic Profiling ◽

Developing Neurons

Abstract BackgroundLoss of tectonin β-propeller repeat-containing 2 (TECPR2) function has been implicated in an array of neurodegenerative disorders, yet its physiological function remains largely unknown. Understanding TECPR2 function is essential for developing much needed precision therapeutics for TECPR2-related diseases. MethodsWe leveraged the considerable amounts of functional data to obtain a comprehensive perspective of the role of TECPR2 in health and disease. We integrated expression patterns, population variation, phylogenetic profiling, protein-protein interactions, and regulatory network data for a minimally biased multimodal functional analysis. Genes and proteins linked to TECPR2 via multiple lines of evidence were subject to functional enrichment analyses to identify molecular mechanisms involving TECPR2.ResultsTECPR2 was found to be part of a tight neurodevelopmental gene expression program that includes KIF1A, ATXN1, TOM1L2, and FA2H, all implicated in neurological diseases. Functional enrichment analyses of TECPR2-related genes converged on a role in late autophagy and ribosomal processes. Large-scale population variation data demonstrated that this role is nonredundant. ConclusionsTECPR2 might serve as an indicator for the energy balance between protein synthesis and autophagy, and a marker for diseases associated with their imbalance, such as Alzheimer’s disease, Huntington’s disease, and various cancers. Our work further suggests that TECPR2 plays a role as a synaptic proteostasis regulator during synaptogenesis, highlighting its importance in developing neurons. By advancing our understanding of TECPR2 function, this work provides an essential stepping stone towards the development of precision diagnostics and targeted treatment options for TECPR2-related disorders.

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Analysis of Expression Profiles of mRNA and lncRNA in Oviduct During Estrus Phase of Sheep (Ovis Aries) with Two Fecundity (FecB Gene) Genotypes

10.21203/rs.3.rs-119198/v1 ◽

2021 ◽

Author(s):

Weihao Chen ◽

Zhifeng Li ◽

Wei Sun ◽

Mingxing Chu

Keyword(s):

Embryo Development ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Interaction Network ◽

Enrichment Analysis ◽

Ovis Aries ◽

Functional Enrichment ◽

Saga Complex ◽

Rna Seq ◽

Estrus Phase

Abstract Background:In sheep, FecB is the essential biomarker of the fertility, previous researches have provided a detailed insight on the regulation involved estrus phase and FecB in the reproductive-related tissues including hypothalamus, pituitary, and ovary. However, as the host of embryo development and connection between the ovary and the uterus, little is known about the interaction between mRNAs and lncRNAs in sheep oviduct. In the present study, RNA-Seq was performed to identify the transcriptomic profiles of mRNAs and lncRNAs in oviduct during estrus phase of sheep with FecBBB/++ genotypes.Results:In total, 21,863 lncRNAs and 43,674 mRNAs were identified, 57 DE lncRNAs and 637 DE mRNAs were revealed in the comparisons between follicular phase and luteal phase, 26 DE lncRNAs and 421 DE lncRNAs were revealed in the comparisons between FecB BB genotype and FecB ++ genotype. Functional enrichment analysis suggested that GO and KEGG terms related to reproduction such as SAGA complex, ATP-binding cassette (ABC), Nestin, and Hippo signalling pathway. DE-interaction network suggested that LNC_018420 maybe the key regulators related to embryo development in sheep oviduct.Conclusion:This was the first study to reveal the transcriptomic profiles of mRNAs and lncRNAs in the oviduct of FecB BB/++ sheep at estrus phase using RNA-Seq. Our findings can provide new understanding on the molecular mechanisms of mRNAs and lncRNAs underlying sheep embryo development and also opening new lines of investigation in sheep reproduction.

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