scholarly journals Integrative Transcriptomic Analysis Reveals the Immune Mechanism for A CyHV-3-Resistant Common Carp Strain

2020 ◽  
Author(s):  
Zhiying Jia ◽  
Nan Wu ◽  
Xiaona Jiang ◽  
Heng Li ◽  
Jiaxin Sun ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Common Carp ◽  
Resistance Mechanism ◽  
Head Kidney ◽  
Immune Gene ◽  
Immune Mechanism ◽  
Protein Coding ◽  
Immune Genes ◽  
Comparison Groups ◽  
Immune Related Genes

ABSTRACTAnti-disease breeding is becoming the most promising solution to cyprinid herpesvirus-3 (CyHV-3) infection, the major threat to common carp aquaculture. Mortality studies suggested that a breeding strain of common carp is resistant to this disease. This study illustrates the immune mechanisms involved in anti-CyHV-3 ability. An integrative analysis of the protein-coding genes and long non-coding RNAs (lncRNAs) using transcriptomic data was also performed. Tissues from the head kidney of common carp were extracted at day 0 (the healthy control) and day 7 after CyHV-3 infection (the survivors), and used to analyze the transcriptome through both Illumina and Pac-bio sequencing. Following analysis of the Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms involved, the immune-related genes were merged. These genes were filtered using the current common carp immune gene library, and information on the immune process was detailed. Immune gene categories and their corresponding genes in different comparison groups were revealed. Also, the immunological Gene Ontology terms for lncRNA modulation were retained. The weighted gene co-expression network analysis was used for the regulation of immune genes lncRNA. The results demonstrated that the breeding carp strain develops marked resistance to CyHV-3 through a specific innate immune mechanism. The featured biological processes were autophagy, phagocytosis, cytotoxicity, and virus blockage by lectins and mucin 3 (MUC3). Moreover, the immune suppressive signals, such as suppression of interleukin 21 receptor (IL21R) on STAT3, PI3K mediated the inhibition of inflammation by dopamine upon infection, as well as the inhibition of NLR family CARD domain containing 3 (NLRC3) on STING during a steady state. Possible susceptible factors for CyHV-3, such as integrin beta 1 (ITGB1), toll-like receptor 18 (TLR18), and C-C motif chemokine ligand 4 (CCL4), were also revealed from the common strain. The results of this study suggested that the regulation of galectin 3 (LGALS3) and T cell leukemia homeobox 3 (TLX3) by lncRNA may play a role in the resistance mechanism. Therefore, immune factors that are immunogenetically insensitive or susceptible to CyHV-3 infection have been revealed.

scholarly journals Integrative Transcriptomic Analysis Reveals the Immune Mechanism for a CyHV-3-Resistant Common Carp Strain

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhiying Jia ◽  
Nan Wu ◽  
Xiaona Jiang ◽  
Heng Li ◽  
Jiaxin Sun ◽  
...  
Keyword(s):  
Common Carp ◽  
Resistance Mechanism ◽  
Head Kidney ◽  
Immune Gene ◽  
Immune Mechanism ◽  
Protein Coding ◽  
Immune Genes ◽  
Kegg Pathways ◽  
Comparison Groups ◽  
Galectin 3

Anti-disease breeding is becoming the most promising solution to cyprinid herpesvirus-3 (CyHV-3) infection, the major threat to common carp aquaculture. Virus challenging studies suggested that a breeding strain of common carp developed resistance to CyHV-3 infection. This study illustrates the immune mechanisms involved in both sensitivity and anti-virus ability for CyHV3 infection in fish. An integrative analysis of the protein-coding genes and long non-coding RNAs (lncRNAs) using transcriptomic data was performed. Tissues from the head kidney of common carp were extracted at days 0 (the healthy control) and 7 after CyHV-3 infection (the survivors) and used to analyze the transcriptome through both Illumina and PacBio sequencing. Following analysis of the GO terms and KEGG pathways involved, the immune-related terms and pathways were merged. To dig out details on the immune aspect, the DEGs were filtered using the current common carp immune gene library. Immune gene categories and their corresponding genes in different comparison groups were revealed. Also, the immunological Gene Ontology terms for lncRNA modulation were retained. The weighted gene co-expression network analysis was used to reveal the regulation of immune genes by lncRNA. The results demonstrated that the breeding carp strain develops a marked resistance to CyHV-3 infection through a specific innate immune mechanism. The featured biological processes were autophagy, phagocytosis, cytotoxicity, and virus blockage by lectins and MUC3. Moreover, the immune-suppressive signals, such as suppression of IL21R on STAT3, PI3K mediated inhibition of inflammation by dopamine upon infection, as well as the inhibition of NLRC3 on STING during a steady state. Possible susceptible factors for CyHV-3, such as ITGB1, TLR18, and CCL4, were also revealed from the non-breeding strain. The results of this study also suggested that Nramp and PAI regulated by LncRNA could facilitate virus infection and proliferation for infected cells respectively, while T cell leukemia homeobox 3 (TLX3), as well as galectin 3 function by lncRNA, may play a role in the resistance mechanism. Therefore, immune factors that are immunogenetically insensitive or susceptible to CyHV-3 infection have been revealed.

scholarly journals Immune gene diversity in archaic and present-day humans

2018 ◽  
Author(s):  
David Reher ◽  
Felix M. Key ◽  
Aida M. Andrés ◽  
Janet Kelso
Keyword(s):  
Gene Diversity ◽  
Innate Immune ◽  
Immune Gene ◽  
Similar Reduction ◽  
Protein Coding ◽  
Immune Genes ◽  
Genome Wide ◽  
Show Evidence ◽  
Functional Consequences ◽  
Immune Related Genes

Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes (gene diversity) was found in exome sequences of three Neandertals. Reduced gene diversity, and particularly in genes involved in immunity, may have important functional consequences. In fact, it has been suggested that reduced diversity in immune genes may have contributed to Neandertal extinction. We therefore explored gene diversity in different human groups and at different time points on the Neandertal lineage with a particular focus on the diversity of genes involved in innate immunity and genes of the Major Histocompatibility Complex (MHC).We find that the two Neandertals and the Denisovan have similar gene diversity, both significantly lower than any present-day human. This is true across gene categories, with no gene set showing an excess decrease in diversity compared to the genome-wide average. Innate immune-related genes show a similar reduction in diversity to other genes, both in present-day and archaic humans. There is also no observable decrease in gene diversity over time in Neandertals, suggesting that there may have been no ongoing reduction in gene diversity in later Neandertals, although this needs confirmation with a larger sample size. In both archaic and present-day humans, genes with the highest levels of diversity are enriched for MHC-related functions. In fact, in archaic humans the MHC genes show evidence of having retained more diversity than genes involved only in the innate immune system.

scholarly journals Identification and development of an independent immune-related genes prognostic model for breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Yuhan Zhang ◽  
Ping Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Risk Scores ◽  
Validation Dataset ◽  
Immune Gene ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Immune Related Genes

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.

scholarly journals Development of a Multi-gene-based Immune Prognostic Signature in Ovarian Cancer

2020 ◽  
Author(s):  
tiefeng cao ◽  
huimin shen
Keyword(s):  
Ovarian Cancer ◽  
Network Analysis ◽  
Prognostic Biomarkers ◽  
Survival Prediction ◽  
Immune Gene ◽  
Prognostic Signature ◽  
Data Set ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Immune Related Genes

Abstract Background：Chemotherapeutic resistance is responsible for treatment failure. Immunotherapy is important in ovarian cancer (OC). Systematic exploration of immunogenic landscape and reliable immune gene-based prognostic biomarkers or signature is necessary to be identified. This study aims to identify the immune gene-based prognostic biomarkers and regulatory factors, further to develop an individualized prediction signature.Methods: This study systematically explored the gene expression profiles from RNA-seq data set for The Cancer Genome Atlas (TCGA) ovarian cancer. Differentially expressed and survival-associated immune genes and transcription factors (TFs) were identified using immune genes from ImmPort dataset and TFs from Cistoma database. We developed the prognostic signature based on survival associated immune genes with LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. Further, Network analysis was performed to uncover the potential molecular mechanisms of immune-related genes with the help of computational biology. Results: The prognostic signature, a weighted combination of the 21 immune-related genes, performed moderately in survival prediction with AUC was 0.746, 0.735, and 0.749 for 1, 3, and 5 year overall survival, respectively. Network analysis uncovered the regulatory role of TFs in immune genes. Intriguingly, the prognostic signature reflected infiltration of some immune cell subtypes.Conclusions: We first constructed a signature with 21 immune genes of clinical significance, which showed promising predictive value in the surveillance, prognosis, even immunotherapy response of OC patients.

scholarly journals Insight from Molecular, Pathological, and Immunohistochemical Studies on Cellular and Humoral Mechanisms Responsible for Vaccine-Induced Protection of Rainbow Trout against Yersinia ruckeri

2013 ◽  
Vol 20 (10) ◽  
pp. 1623-1641 ◽  
Author(s):  
Sidhartha Deshmukh ◽  
Per W. Kania ◽  
Jiwan K. Chettri ◽  
Jakob Skov ◽  
Anders M. Bojesen ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Acute Phase Proteins ◽  
Head Kidney ◽  
Yersinia Ruckeri ◽  
Content Type ◽  
Immune Genes ◽  
Immunological Mechanisms ◽  
Genes Encoding ◽  
Immune Related Genes

ABSTRACTThe immunological mechanisms associated with protection of vaccinated rainbow trout,Oncorhynchus mykiss, against enteric redmouth disease (ERM), caused byYersinia ruckeri, were previously elucidated by the use of gene expression methodology and immunochemical methods. That approach pointed indirectly to both humoral and cellular elements being involved in protection. The present study correlates the level of protection in rainbow trout to cellular reactions in spleen and head kidney and visualizes the processes by applying histopathological, immunohistochemical, andin situhybridization techniques. It was shown that these cellular reactions, which were more prominent in spleen than in head kidney, were associated with the expression of immune-related genes, suggesting a Th2-like response.Y. ruckeri, as shown byin situhybridization (ISH), was eliminated within a few days in vaccinated fish, whereas nonprotected fish still harbored bacteria for a week after infection. Vaccinated fish reestablished normal organ structure within a few days, whereas nonprotected fish showed abnormalities up to 1 month postinfection. Protection in the early phase of infection was mainly associated with the expression of genes encoding innate factors (complement factors, lysozyme, and acute phase proteins), but in the later phase of infection, increased expression of adaptive immune genes dominated. The histological approach used has shown that the cellular changes correlated with protection of vaccinated fish. They comprised transformation of resident cells into macrophage-like cells and increased occurrence of CD8α and IgM cells, suggesting these cells as main players in protection. Future studies should investigate the causality between these factors and protection.

scholarly journals Development of a Multi-gene-based Immune Prognostic Signature in Ovarian Cancer

2021 ◽  
Author(s):  
tiefeng cao ◽  
huimin shen
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Network Analysis ◽  
Survival Prediction ◽  
Immune Gene ◽  
Prognostic Signature ◽  
Data Set ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Immune Related Genes

Abstract Background： Various components of the immune system play a critical role in the prognosis and treatment response in ovarian cancer (OC). Immunotherapy has been recognized as a hallmark of cancer but the effect is contradictional. Reliable immune gene-based prognostic biomarkers or regulatory factors are necessary to be systematically explored to develop an individualized prediction signature.Methods: This study systematically explored the gene expression profiles in patients with ovarian cancer from RNA-seq data set for The Cancer Genome Atlas (TCGA). Differentially expressed immune genes and transcription factors (TFs) were identified using the collected immune genes from ImmPort dataset and TFs from Cistoma database. Survival associated immune genes and TFs were identified in terms of overall survival. The prognostic signature was developed based on survival associated immune genes with LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. Further, we performed network analysis to uncover the potential regulators of immune-related genes with the help of computational biology. Results: The prognostic signature, a weighted combination of the 21 immune-related genes, performed moderately in survival prediction with AUC was 0.746, 0.735, and 0.749 for 1, 3, and 5 year overall survival, respectively. Network analysis uncovered the regulatory role of TFs in immune genes. Intriguingly, the prognostic signature reflected the immune cells landscape and infiltration of some immune cell subtypes.Conclusions: We first constructed a signature with 21 immune genes of clinical significance, which showed promising predictive value in the surveillance, and prognosis of OC patients.

scholarly journals Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaojun Hu ◽  
Xiusheng Qu ◽  
Yu Jiao ◽  
Jiahui Hu ◽  
Bo Wang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Drug Sensitivity ◽  
Triple Negative ◽  
Cox Regression ◽  
Landscape Analysis ◽  
Immune Gene ◽  
Immune Genes ◽  
New Perspective ◽  
Immune Related Genes

Background: To classify triple-negative breast cancer (TNBC) immunotyping using the public database, analyze the differences between subtypes in terms of clinical characteristics and explore the role and clinical significance of immune subtypes in TNBC immunotherapy.Methods: We downloaded TNBC data from the cBioPortal and GEO databases. The immune genes were grouped to obtain immune gene modules and annotate their biological functions. Log-rank tests and Cox regression were used to evaluate the prognosis of immune subtypes (IS). Drug sensitivity analysis was also performed for the differences among immune subtypes in immunotherapy and chemotherapy. In addition, dimension reduction analysis based on graph learning was utilized to reveal the internal structure of the immune system and visualize the distribution of patients.Results: Significant differences in prognosis were observed between subtypes (IS1, IS2, and IS3), with the best in IS3 and the worst in IS1. The sensitivity of IS3 to immunotherapy and chemotherapy was better than the other two subtypes. In addition, Immune landscape analysis found the intra-class heterogeneity of immune subtypes and further classified IS3 subtypes (IS3A and IS3B). Immune-related genes were divided into seven functional modules (The turquoise module has the worst prognosis). Five hub genes (RASSF5, CD8A, ICOS, IRF8, and CD247) were screened out as the final characteristic genes related to poor prognosis by low expression.Conclusions: The immune subtypes of TNBC were significantly different in prognosis, gene mutation, immune infiltration, drug sensitivity, and heterogeneity. We validated the independent role of immune subtypes in tumor progression and immunotherapy for TNBC. This study provides a new perspective for personalized immunotherapy and the prognosis evaluation of TNBC patients in the future.

scholarly journals Development of a multi-gene-based immune prognostic signature in ovarian Cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tiefeng Cao ◽  
Huimin Shen
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Network Analysis ◽  
Survival Prediction ◽  
Immune Gene ◽  
Prognostic Signature ◽  
Data Set ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Immune Related Genes

Abstract Background Various components of the immune system play a critical role in the prognosis and treatment response in ovarian cancer (OC). Immunotherapy has been recognized as a hallmark of cancer but the effect is contradictional. Reliable immune gene-based prognostic biomarkers or regulatory factors are necessary to be systematically explored to develop an individualized prediction signature. Methods This study systematically explored the gene expression profiles in patients with ovarian cancer from RNA-seq data set for The Cancer Genome Atlas (TCGA). Differentially expressed immune genes and transcription factors (TFs) were identified using the collected immune genes from ImmPort dataset and TFs from Cistoma database. Survival associated immune genes and TFs were identified in terms of overall survival. The prognostic signature was developed based on survival associated immune genes with LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. Further, we performed network analysis to uncover the potential regulators of immune-related genes with the help of computational biology. Results The prognostic signature, a weighted combination of the 21 immune-related genes, performed moderately in survival prediction with AUC was 0.746, 0.735, and 0.749 for 1, 3, and 5 year overall survival, respectively. Network analysis uncovered the regulatory role of TFs in immune genes. Intriguingly, the prognostic signature reflected the immune cells landscape and infiltration of some immune cell subtypes. Conclusions We first constructed a signature with 21 immune genes of clinical significance, which showed promising predictive value in the surveillance, and prognosis of OC patients.

scholarly journals Effect of chrysophanic acid on immune response and immune genes transcriptomic profile in Catla catla against Aeromonas hydrophila

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ramasamy Harikrishnan ◽  
Gunapathy Devi ◽  
Chellam Balasundaram ◽  
Hien Van Doan ◽  
Sanchai Jaturasitha ◽  
...  
Keyword(s):  
Aeromonas Hydrophila ◽  
Head Kidney ◽  
Catla Catla ◽  
Mrna Transcription ◽  
Gene Profile ◽  
Superoxide Anion Production ◽  
Immune Genes ◽  
Tnf Α ◽  
Immune Related Genes ◽  
Oxide Synthase

AbstractThe effect of chrysophanic acid (CA) (2, 4, and 8 mg kg−1) on the immunity and immune-related gene profile of Catla catla against Aeromonas hydrophila is reported. In both control and treated groups fed with 2 mg kg−1 (2 CA), the phagocytosis, hemolytic, myeloperoxidase content, and superoxide anion production decreased significantly between 6th and 8th weeks, whereas when fed with 4 mg kg−1 CA (4 CA) the H2O2 production and nitric oxide synthase increased significantly between 4th and 8th week. When fed with 2 CA and 4 CA diets, the total protein, bactericidal, and antibody titer increased significantly from the 4th week onwards. When fed with 2 CA, the IL-1β and IL-10 mRNA expression of head kidney leucocytes were significant between weeks 6 and 8. The expressions of toll-like receptors significantly increased when fed with a 4 CA diet from 4th week onwards. The 4 CA group significantly increased in TNF-α, TNF receptor-associated factor 6 (NOD), which influences protein expression, after the 4th week. The mRNA transcription of MHCI, lysozyme-chicken and goose type expressions significantly increased in 4 CA group within the 4th week. In summary, the dietary administration of 4 mg kg−1 of CA (4 CA) provides better immunity and enhances the up-regulation of immune-related genes in Catla against A. hydrophila.

Identification of molecular subtyping system and four-gene prognostic signature with immune-related genes for uveal melanoma

2021 ◽  
pp. 153537022110538
Author(s):  
Fei Xia ◽  
Zhilong Yu ◽  
Aijun Deng ◽  
Guohong Gao
Keyword(s):  
Uveal Melanoma ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
Enrichment Score ◽  
Immune Gene ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Gene Modules ◽  
Melanoma Patients ◽  
Immune Related Genes

Immunotherapy is the most promising treatment for uveal melanoma patients with metastasis. Tumor microenvironment plays an essential role in tumor progression and greatly affects the efficacy of immunotherapy. This research constructed an immune-related subtyping system and discovered immune prognostic genes to further understand the immune mechanism in uveal melanoma. Immune-related genes were determined from literature. Gene expression profiles of uveal melanoma were clustered using consensus clustering based on immune-related genes. Subtypes were further divided by applying immune landscape, and weighted correlation network analysis was performed to construct immune gene modules. Univariate Cox regression analysis was conducted to generate a prognostic model. Enriched immune cells were determined after gene set enrichment analysis. Three major immune subtypes (IS1, IS2, and IS3) were identified, and IS2 could be further divided into IS2A and IS2B. The subtypes were closely associated with uveal melanoma prognosis. IS3 group had the most favorable prognosis and was sensitive to PD-1 inhibitor. Immune genes in IS1 group showed an overall higher expression than IS3 group. Six immune gene modules were identified, and the enrichment score of immune genes varied within immune subtypes. Four immune prognostic genes ( IL32, IRF1, SNX20, and VAV1) were found to be closely related to survival. This novel immune subtyping system and immune landscape provide a new understanding of immunotherapy in uveal melanoma. The four prognostic genes can predict prognosis of uveal melanoma patients and contribute to new development of targeted drugs.

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