scholarly journals Identification of Radiotherapy-Associated Genes in Lung Adenocarcinoma by an Integrated Bioinformatics Analysis Approach

2021 ◽  
Vol 8 ◽  
Author(s):  
Junhao Wang ◽  
Qizheng Han ◽  
Huizi Liu ◽  
Haihua Luo ◽  
Lei Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Types ◽  
Specific Gene ◽  
Hub Genes ◽  
Drug Candidates ◽  
Interaction Database ◽  
Potential Association ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
Gene Expression Levels

Radiotherapy (RT) plays an important role in the prognosis of lung adenocarcinoma (LUAD) patients, but the radioresistance (RR) of LUAD is still a challenge that needs to be overcome. The current study aimed to investigate LUAD patients with RR to illuminate the underlying mechanisms. We utilized gene set variation analysis (GSVA) and The Cancer Immunome Atlas (TCIA) database to characterize the differences in biological functions and neoantigen-coding genes between RR and radiosensitive (RS) patients. Weighted Gene co-expression network analysis (WGCNA) was used to explore the relationship between RT-related traits and hub genes in two modules, i.e., RR and RS; two representative hub genes for RR (MZB1 and DERL3) and two for RS (IFI35 and PSMD3) were found to be related to different RT-related traits. Further analysis of the hub genes with the Lung Cancer Explorer (LCE), PanglaoDB and GSVA resources revealed the differences in gene expression levels, cell types and potential functions. On this basis, the Tumor and Immune System Interaction Database (TISIDB) was used to identify the potential association between RR genes and B cell infiltration. Finally, we used the Computational Analysis of Resistance (CARE) database to identify specific gene-associated drugs for RR patients and found that GSK525762A and nilotinib might be promising candidates for RR treatment. Taken together, these results demonstrate that B cells in TME may have a significant impact on the RT and that these two drug candidates, GSK525762A and nilotinib, might be helpful for the treatment of RR patients.

scholarly journals ImmuneRegulation: a web-based tool for identifying human immune regulatory elements

2019 ◽  
Vol 47 (W1) ◽  
pp. W142-W150 ◽  
Author(s):  
Selim Kalayci ◽  
Myvizhi Esai Selvan ◽  
Irene Ramos ◽  
Chris Cotsapas ◽  
Eva Harris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Web Based ◽  
Transcriptome Regulation ◽  
Rich Data ◽  
User Friendly ◽  
Gene Expression Levels

Abstract Humans vary considerably both in their baseline and activated immune phenotypes. We developed a user-friendly open-access web portal, ImmuneRegulation, that enables users to interactively explore immune regulatory elements that drive cell-type or cohort-specific gene expression levels. ImmuneRegulation currently provides the largest centrally integrated resource on human transcriptome regulation across whole blood and blood cell types, including (i) ∼43,000 genotyped individuals with associated gene expression data from ∼51,000 experiments, yielding genetic variant-gene expression associations on ∼220 million eQTLs; (ii) 14 million transcription factor (TF)-binding region hits extracted from 1945 ChIP-seq studies; and (iii) the latest GWAS catalog with 67,230 published variant-trait associations. Users can interactively explore associations between queried gene(s) and their regulators (cis-eQTLs, trans-eQTLs or TFs) across multiple cohorts and studies. These regulators may explain genotype-dependent gene expression variations and be critical in selecting the ideal cohorts or cell types for follow-up studies or in developing predictive models. Overall, ImmuneRegulation significantly lowers the barriers between complex immune regulation data and researchers who want rapid, intuitive and high-quality access to the effects of regulatory elements on gene expression in multiple studies to empower investigators in translating these rich data into biological insights and clinical applications, and is freely available at https://immuneregulation.mssm.edu.

scholarly journals Bioinformatics Approach to Identify Common Gene Signatures of Patients With Coronavirus 2019 and Lung Adenocarcinoma

2021 ◽  
Author(s):  
Xiao Liang ◽  
Yali Chen ◽  
Yuchao Fan
Keyword(s):  
Lung Adenocarcinoma ◽  
Severe Disease ◽  
Enrichment Analysis ◽  
Immune Checkpoints ◽  
Specific Gene ◽  
Ppi Network ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Tf Gene

Abstract Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman’s correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), cellular component (CC) as well as to pathways, specific organs, cells and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.

scholarly journals Fast and powerful statistical method for context-specific QTL mapping in multi-context genomic studies

2021 ◽  
Author(s):  
Andrew Lu ◽  
Mike Thompson ◽  
M Grace Gordon ◽  
Andy Dahl ◽  
Chun Jimmie Ye ◽  
...  
Keyword(s):  
Fold Increase ◽  
Cell Types ◽  
Specific Gene ◽  
Data Sets ◽  
Rna Seq ◽  
Computationally Efficient ◽  
Genomic Studies ◽  
Cell Type Specific ◽  
Context Specific ◽  
The Relationship

Recent studies suggest that context-specific eQTLs underlie genetic risk factors for complex diseases. However, methods for identifying them are still nascent, limiting their comprehensive characterization and downstream interpretation of disease-associated variants. Here, we introduce FastGxC, a method to efficiently and powerfully map context-specific eQTLs by leveraging the correlation structure of multi-context studies. We first show via simulations that FastGxC is orders of magnitude more powerful and computationally efficient than previous approaches, making previously year-long computations possible in minutes. We next apply FastGxC to bulk multi-tissue and single-cell RNA-seq data sets to produce the most comprehensive tissue- and cell-type-specific eQTL maps to date. We then validate these maps by establishing that context-specific eQTLs are enriched in corresponding functional genomic annotations. Finally, we examine the relationship between context-specific eQTLs and human disease and show that FastGxC context-specific eQTLs provide a three-fold increase in precision to identify relevant tissues and cell types for GWAS variants than standard eQTLs. In summary, FastGxC enables the construction of context-specific eQTL maps that can be used to understand the context-specific gene regulatory mechanisms underlying complex human diseases.

scholarly journals The Interaction Between Microglia and Macroglia in Glaucoma

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaohuan Zhao ◽  
Rou Sun ◽  
Xueting Luo ◽  
Feng Wang ◽  
Xiaodong Sun
Keyword(s):  
Glial Cells ◽  
Vision Loss ◽  
Inflammatory Responses ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Treatment Options ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Underlying Mechanisms ◽  
The Relationship

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Unfortunately, the underlying mechanisms behind such cases remain unclear. Recent studies have suggested that retinal glia play significant roles in the initiation and progression of glaucoma. Multiple types of glial cells are activated in glaucoma. Microglia, for example, act as critical mediators that orchestrate the progression of neuroinflammation through pro-inflammatory cytokines. In contrast, macroglia (astrocytes and Müller cells) participate in retinal inflammatory responses as modulators and contribute to neuroprotection through the secretion of neurotrophic factors. Notably, research results have indicated that intricate interactions between microglia and macroglia might provide potential therapeutic targets for the prevention and treatment of glaucoma. In this review, we examine the specific roles of microglia and macroglia in open-angle glaucoma, including glaucoma in animal models, and analyze the interaction between these two cell types. In addition, we discuss potential treatment options based on the relationship between glial cells and neurons.

scholarly journals Microdissection of the Bulk Transcriptome at Single-Cell Resolution Reveals Clinical Significance and Myeloid Cells Heterogeneity in Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Wu ◽  
Jiale Qin ◽  
Qiang Zhao ◽  
Lu Lu ◽  
Chen Li
Keyword(s):  
Lung Adenocarcinoma ◽  
Single Cell ◽  
Immune Therapy ◽  
Myeloid Cell ◽  
Cell Types ◽  
Specific Gene ◽  
Inflammasome Activation ◽  
Cell Type ◽  
Time Saving ◽  
Cell Type Specific

BackgroundTumor infiltrating myeloid (TIM) cells constitute a vital element of the tumor microenvironment. The cell-type heterogeneity of TIM has yet to be fully investigated.MethodsWe used a time saving approach to generate a single-cell reference matrix, allowing quantification of cell-type proportions and cell-type-specific gene abundances in bulk RNA-seq data.ResultsTwo distinct clusters, MSC1 and MSC2 (MSC subtype) were newly identified in lung adenocarcinoma (LUAD) patients, both significantly associated with overall survival and immune blockade therapy responses. Twenty myeloid cell types were detected. Thirteen of these had distinct enrichment patterns between MSC1 and MSC2. LAMP3+ dendritic cells, being a mature and transportable subtype of dendritic cell that may migrate to lymph nodes, were noted as associated with non-responsiveness to immunotargeted therapy. High infiltration level of IFIT3+ neutrophils was strongly related to the response to immune-targeted therapy and was seen to activate CD8+ T cells, partly through inflammasome activation. The infiltration levels of TIMP1+ macrophages and S100A8+ neutrophils were both significantly associated with poor prognosis. TIMP1+ macrophages were noted to recruit S100A8+ neutrophils via the CXCL5–CXCR2 axes and promote LUAD progression.ConclusionAltogether, we performed virtual microdissection of the bulk transcriptome at single-cell resolution and provided a promising TIM infiltration landscape that may shed new light on the development of immune therapy.

scholarly journals GBP4 is an Accurate Diagnostic Biomarker and a Potential Treatment Target for Crohn’s Disease

2021 ◽  
Author(s):  
Heng Shi ◽  
Qin Peng ◽  
Xian-Ling Zhou ◽  
Shi-Ping Zhu ◽  
Sheng-Yun Sun
Keyword(s):  
Intestinal Mucosa ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Strongly Correlated ◽  
Healthy Individuals ◽  
Hub Genes ◽  
M1 Macrophages ◽  
Pathway Enrichment ◽  
The Relationship

Abstract Background: Extensive evidence has shown that immune cell infiltration is associated with the pathogenesis of Crohn’s disease (CD). In the present study, we explored the potential mechanism underlying the pathogenesis biomarkers for CD.Methods: The GSE179285 dataset containing sequence data for intestinal mucosal was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in the intestinal mucosa of CD patients and healthy individuals were then identified. The infiltration pattern of 22 immune cell types was assessed using the CIBERSORT algorithm. The DEGs and 22 immune cell types were combined to find the key gene network using weighted gene co-expression network analysis (WGCNA), and pathway enrichment analyzes were performed on the hub module in the WGCNA. A linear regression model for the relationship between the expression of the hub genes in CD patients and infiltration of immune cells were also developed. The utility and accuracy of the hub genes for CD diagnosis were assessed using receiver operating characteristic (ROC) analysis. The accuracy of the model was validated using GSE20881 dataset. Results: There were 1135 DEGs between the intestinal mucosal tissue of CD patients and healthy individuals. Of these DEGs, 711 genes were upregulated, whereas 424 of them were downregulated. There was also a significant difference in the infiltration of immune cells to the intestinal mucosal between the CD patients and healthy individuals. WGCNA revealed that the turquoise module genes were strongly correlated with the infiltration of M1 macrophages (cor=0.68, p=10-16). Pathway enrichment analysis further showed the genes in the turquoise module mainly regulated the secretion of interferon-gamma and other immune effector molecules. Finally, the expression of GBP4, the identified hub gene, strongly correlated with the infiltration of M1 macrophages (adjusted r-squared=0.661, p<2x10-16), and is a relatively good marker for CD diagnostic prediction (AUC=0.736). The relationship between GBP4 expression and infiltration of M1 macrophages (adjusted r-squared=0.435, p<2x10-16) and prognostic value of the gene (AUC=0.702) were verified using the GSE20881 validation dataset.Conclusion: GBP4 is a potential biomarker for accurate CD diagnosis. The expression of GBP4 promotes the infiltration of M1 macrophages to the intestinal mucosa of CD patients.

scholarly journals Identification of Key Genes and Pathways in Gefitinib-Resistant Lung Adenocarcinoma using Bioinformatics Analysis

2021 ◽  
Vol 17 ◽  
pp. 117693432110237
Author(s):  
Kailin Mao ◽  
Fang Lin ◽  
Yingai Zhang ◽  
Hailong Zhou
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Underlying Mechanisms ◽  
Gefitinib Resistance

Gefitinib resistance is a serious threat in the treatment of patients with non-small cell lung cancer (NSCLC). Elucidating the underlying mechanisms and developing effective therapies to overcome gefitinib resistance is urgently needed. The differentially expressed genes (DEGs) were screened from the gene expression profile GSE122005 between gefitinib-sensitive and resistant samples. GO and KEGG analyses were performed with DAVID. The protein-protein interaction (PPI) network was established to visualize DEGs and screen hub genes. The functional roles of CCL20 in lung adenocarcinoma (LUAD) were examined using gene set enrichment analysis (GSEA). Functional analysis revealed that the DEGs were mainly concentrated in inflammatory, cell chemotaxis, and PI3K signal regulation. Ten hub genes were identified based on the PPI network. The survival analysis of the hub genes showed that CCL20 had a significant effect on the prognosis of LUAD patients. GSEA analysis showed that CCL20 high expression group was mainly enriched in cytokine-related signaling pathways. In conclusion, our analysis suggests that changes in inflammation and cytokine-related signaling pathways are closely related to gefitinib resistance in patients with lung cancer. The CCL20 gene may promote the formation of gefitinib resistance, which may serve as a new biomarker for predicting gefitinib resistance in patients with lung cancer.

Management of Platelets in a Persian Girl with the Tetralogy_Pantalogy of Fallot (Tof_Pof): A Case Report Study

2020 ◽  
Author(s):  
Bahram Alamdary Badlou
Keyword(s):  
Case Report ◽  
Ventricular Septal Defect ◽  
Atrial Septal Defect ◽  
Sleep Disorders ◽  
Social Life ◽  
Rare Case ◽  
Septal Defect ◽  
Old Persian ◽  
Underlying Mechanisms ◽  
The Relationship

We report a rare case of unrepaired Tetralogy_Pantalogy of Fallot (TOF_POF) in a 20 years old Persian girl Mrs Zeynab S., who presented with cyanotic finger tops appearance, ongoing chronic thrombolytic destruction processes, and remarkable thrombocytopenia [1,2], heart ventricular septal defect (VSD), and might atrial septal defect (ASD), anxiety, sleep disorders, nightmares, and limited social life. Additionally, the relationship between underlying mechanisms, possible treatments of the thrombocytopenia, erythrocytosis, and unrepaired cardiovascular leakages remains unknown.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

scholarly journals Conditional regard, stress, and dyadic adjustment in primiparous couples: A dyadic analysis perspective

2021 ◽  
pp. 026540752199356
Author(s):  
Alexandra Cournoyer ◽  
Julie C. Laurin ◽  
Marie-Ève Daspe ◽  
Sophie Laniel ◽  
Anne-Sophie Huppé
Keyword(s):  
Transition To Parenthood ◽  
Psychological Needs ◽  
Basic Psychological Needs ◽  
Dyadic Adjustment ◽  
Dyadic Analysis ◽  
Mediation Model ◽  
Online Questionnaire ◽  
Mediating Role ◽  
Underlying Mechanisms ◽  
The Relationship

Many couples transitioning into parenthood are at risk for dyadic adjustment declines. It is therefore important to explore key, theory-driven deterrents of enduring relationships during this period, as well as potential underlying mechanisms. This study examined the relationship between perceived conditional negative regard (i.e. a behavior that thwarts basic psychological needs; T1), stress (T1), and dyadic adjustment (T2) during the transition to parenthood. Primiparous couples ( N = 144) were recruited to fill out an online questionnaire when their babies were 6-months (T1) and 12-months (T2). Path analysis with an Actor-Partner Interdependence Mediation Model was conducted. Results show that for each partner (actor effects), stress (T1) mediated the link between perceived conditional negative regard (T1), and later dyadic adjustment (T2). For the partner effects, while stress (T1) did not play a mediating role between these variables, other partner effects were found. Each primiparous parent’s perceived conditional negative regard (T1) was associated with the other parent’s later dyadic adjustment (T2). However, when examining longitudinal changes in stress and dyadic adjustment over time (T2, controlling for respective T1), no significant associations were found. Overall, the findings shed light on the dyadic associations of conditional negative regard, and the mechanisms through which it is negatively tied with dyadic adjustment during the transition to parenthood.

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