scholarly journals RNA-seq driven expression and enrichment analysis to investigate CVD genes with associated phenotypes among high-risk heart failure patients

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Zeeshan Ahmed ◽  
Saman Zeeshan ◽  
Bruce T. Liang
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Genetic Associations ◽  
Specific Analysis ◽  
Gender Specific ◽  
Unique Genes

Abstract Background Heart failure (HF) is one of the most common complications of cardiovascular diseases (CVDs) and among the leading causes of death in the US. Many other CVDs can lead to increased mortality as well. Investigating the genetic epidemiology and susceptibility to CVDs is a central focus of cardiology and biomedical life sciences. Several studies have explored expression of key CVD genes specially in HF, yet new targets and biomarkers for early diagnosis are still missing to support personalized treatment. Lack of gender-specific cardiac biomarker thresholds in men and women may be the reason for CVD underdiagnosis in women, and potentially increased morbidity and mortality as a result, or conversely, an overdiagnosis in men. In this context, it is important to analyze the expression and enrichment of genes with associated phenotypes and disease-causing variants among high-risk CVD populations. Methods We performed RNA sequencing focusing on key CVD genes with a great number of genetic associations to HF. Peripheral blood samples were collected from a broad age range of adult male and female CVD patients. These patients were clinically diagnosed with CVDs and CMS/HCC HF, as well as including cardiomyopathy, hypertension, obesity, diabetes, asthma, high cholesterol, hernia, chronic kidney, joint pain, dizziness and giddiness, osteopenia of multiple sites, chest pain, osteoarthritis, and other diseases. Results We report RNA-seq driven case–control study to analyze patterns of expression in genes and differentiating the pathways, which differ between healthy and diseased patients. Our in-depth gene expression and enrichment analysis of RNA-seq data from patients with mostly HF and other CVDs on differentially expressed genes and CVD annotated genes revealed 4,885 differentially expressed genes (DEGs) and regulation of 41 genes known for HF and 23 genes related to other CVDs, with 15 DEGs as significantly expressed including four genes already known (FLNA, CST3, LGALS3, and HBA1) for HF and CVDs with the enrichment of many pathways. Furthermore, gender and ethnic group specific analysis showed shared and unique genes between the genders, and among different races. Broadening the scope of the results in clinical settings, we have linked the CVD genes with ICD codes. Conclusions Many pathways were found to be enriched, and gender-specific analysis showed shared and unique genes between the genders. Additional testing of these genes may lead to the development of new clinical tools to improve diagnosis and prognosis of CVD patients.

scholarly journals Bioinformatics-based Screening of Key Genes for Saponin Metabolism in Quinoa

2021 ◽  
Author(s):  
Chengang Guo ◽  
Zhimin wei ◽  
Wei Lyu ◽  
Yanlou Geng
Keyword(s):  
Differentially Expressed Genes ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Hierarchical Cluster ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Differential Analysis ◽  
Rna Seq ◽  
Protein Coding ◽  
Key Genes

Abstract Quinoa saponins have complex, diverse and evident physiologic activities. However, the key regulatory genes for quinoa saponin metabolism are not yet well studied. The purpose of this study was to explore genes closely related to quinoa saponin metabolism. In this study, the significantly differentially expressed genes in yellow quinoa were firstly screened based on RNA-seq technology. Then, the key genes for saponin metabolism were selected by gene set enrichment analysis (GSEA) and principal component analysis (PCA) statistical methods. Finally, the specificity of the key genes was verified by hierarchical clustering. The results of differential analysis showed that 1654 differentially expressed genes were achieved after pseudogenes deletion. Therein, there were 142 long non-coding genes and 1512 protein-coding genes. Based on GSEA analysis, 116 key candidate genes were found to be significantly correlated with quinoa saponin metabolism. Through PCA dimension reduction analysis, 57 key genes were finally obtained. Hierarchical cluster analysis further demonstrated that these key genes can clearly separate the four groups of samples. The present results could provide references for the breeding of sweet quinoa and would be helpful for the rational utilization of quinoa saponins.

scholarly journals Insights into the Synthesis, Secretion and Curing of Barnacle Cyprid Adhesive via Transcriptomic and Proteomic Analyses of the Cement Gland

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 186
Author(s):  
Guoyong Yan ◽  
Jin Sun ◽  
Zishuai Wang ◽  
Pei-Yuan Qian ◽  
Lisheng He
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Lysyl Oxidase ◽  
Enrichment Analysis ◽  
Salivary Secretion ◽  
Cement Gland ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Rna Seq ◽  
Secretion Pathway

Barnacles represent one of the model organisms used for antifouling research, however, knowledge regarding the molecular mechanisms underlying barnacle cyprid cementation is relatively scarce. Here, RNA-seq was used to obtain the transcriptomes of the cement glands where adhesive is generated and the remaining carcasses of Megabalanus volcano cyprids. Comparative transcriptomic analysis identified 9060 differentially expressed genes, with 4383 upregulated in the cement glands. Four cement proteins, named Mvcp113k, Mvcp130k, Mvcp52k and Mvlcp1-122k, were detected in the cement glands. The salivary secretion pathway was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed genes, implying that the secretion of cyprid adhesive might be analogous to that of saliva. Lysyl oxidase had a higher expression level in the cement glands and was speculated to function in the curing of cyprid adhesive. Furthermore, the KEGG enrichment analysis of the 352 proteins identified in the cement gland proteome partially confirmed the comparative transcriptomic results. These results present insights into the molecular mechanisms underlying the synthesis, secretion and curing of barnacle cyprid adhesive and provide potential molecular targets for the development of environmentally friendly antifouling compounds.

scholarly journals Identification of CDC20 as a Novel Biomarker in Diagnosis and Treatment of Wilms Tumor

2021 ◽  
Vol 9 ◽  
Author(s):  
Qinlin Shi ◽  
Bo Tang ◽  
Yanping Li ◽  
Yonglin Li ◽  
Tao Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Wilms Tumor ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Ppi Network ◽  
And Migration ◽  
Proliferation And Migration

Objective: Wilms tumor (WT) is a common malignant solid tumor in children. Many tumor biomarkers have been reported; however, there are poorly targetable molecular mechanisms which have been defined in WT. This study aimed to identify the oncogene in WT and explore the potential mechanisms.Methods: Differentially expressed genes (DEGs) in three independent RNA-seq datasets were downloaded from The Cancer Genome Atlas data portal and the Gene Expression Omnibus database (GSE66405 and GSE73209). The common DEGs were then subjected to Gene Ontology enrichment analysis, protein–protein interaction (PPI) network analysis, and gene set enrichment analysis. The protein expression levels of the hub gene were analyzed by immunohistochemical analysis and Western blotting in a 60 WT sample. The univariate Kaplan–Meier analysis for overall survival was performed, and the log-rank test was utilized. A small interfering RNA targeting cell division cycle 20 (CDC20) was transfected into G401 and SK-NEP-1 cell lines. The Cell Counting Kit-8 assay and wound healing assay were used to observe the changes in cell proliferation and migration after transfection. Flow cytometry was used to detect the effect on the cell cycle. Western blot was conducted to study the changes of related functional proteins.Results: We commonly identified 44 upregulation and 272 downregulation differentially expressed genes in three independent RNA-seq datasets. Gene and pathway enrichment analyses of the regulatory networks involving hub genes suggested that cell cycle changes are crucial in WT. The top 15 highly connected genes were found by PPI network analysis. Furthermore, we demonstrated that one candidate biomarker, CDC20, for the diagnosis of WT was detected, and its high expression predicted poor prognosis of WT patients. Moreover, the area under the curve value obtained by receiver operating characteristic curve analysis from paired WT samples was 0.9181. Finally, we found that the suppression of CDC20 inhibited proliferation and migration and resulted in G2/M phase arrest in WT cells. The mechanism may be involved in increasing the protein level of securin, cyclin B1, and cyclin AConclusion: Our results suggest that CDC20 could serve as a candidate diagnostic and prognostic biomarker for WT, and suppression of CDC20 may be a potential approach for the prevention and treatment of WT.

scholarly journals Construction of a Prognostic Immune-Related LncRNA Risk Model for Lung Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Yue Li ◽  
Ruoyi Shen ◽  
Anqi Wang ◽  
Jian Zhao ◽  
Jieqi Zhou ◽  
...  
Keyword(s):  
High Risk ◽  
Differentially Expressed Genes ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Enrichment Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Differentially Expressed ◽  
Cox Regression Analysis

BackgroundLung adenocarcinoma (LUAD) originates mainly from the mucous epithelium and glandular epithelium of the bronchi. It is the most common pathologic subtype of non-small cell lung cancer (NSCLC). At present, there is still a lack of clear criteria to predict the efficacy of immunotherapy. The 5-year survival rate for LUAD patients remains low.MethodsAll data were downloaded from The Cancer Genome Atlas (TCGA) database. We used Gene Set Enrichment Analysis (GSEA) database to obtain immune-related mRNAs. Immune-related lncRNAs were acquired by using the correlation test of the immune-related genes with R version 3.6.3 (Pearson correlation coefficient cor = 0.5, P < 0.05). The TCGA-LUAD dataset was divided into the testing set and the training set randomly. Based on the training set to perform univariate and multivariate Cox regression analyses, we screened prognostic immune-related lncRNAs and given a risk score to each sample. Samples were divided into the high-risk group and the low-risk group according to the median risk score. By the combination of Kaplan–Meier (KM) survival curve, the receiver operating characteristic (ROC) (AUC) curve, the independent risk factor analysis, and the clinical data of the samples, we assessed the accuracy of the risk model. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the differentially expressed mRNAs between the high-risk group and the low-risk group. The differentially expressed genes related to immune response between two risk groups were analyzed to evaluate the role of the model in predicting the efficacy and effects of immunotherapy. In order to explain the internal mechanism of the risk model in predicting the efficacy of immunotherapy, we analyzed the differentially expressed genes related to epithelial-mesenchymal transition (EMT) between two risk groups. We extracted RNA from normal bronchial epithelial cell and LUAD cells and verified the expression level of lncRNAs in the risk model by a quantitative real-time polymerase chain reaction (qRT-PCR) test. We compared our risk model with other published prognostic signatures with data from an independent cohort. We transfected LUAD cell with siRNA-LINC0253. Western blot analysis was performed to observed change of EMT-related marker in protein level.ResultsThrough univariate Cox regression analysis, 24 immune-related lncRNAs were found to be strongly associated with the survival of the TCGA-LUAD dataset. Utilizing multivariate Cox regression analysis, 10 lncRNAs were selected to establish the risk model. The K-M survival curves and the ROC (AUC) curves proved that the risk model has a fine predictive effect. The GO enrichment analysis indicated that the effect of the differentially expressed genes between high-risk and low-risk groups is mainly involved in immune response and intercellular interaction. The KEGG enrichment analysis indicated that the differentially expressed genes between high-risk and low-risk groups are mainly involved in endocytosis and the MAPK signaling pathway. The expression of genes related to the efficacy of immunotherapy was significantly different between the two groups. A qRT-PCR test verified the expression level of lncRNAs in LUAD cells in the risk model. The AUC of ROC of 5 years in the independent validation dataset showed that this model had superior accuracy. Western blot analysis verified the change of EMT-related marker in protein level.ConclusionThe immune lncRNA risk model established by us could better predict the prognosis of patients with LUAD.

scholarly journals Enrichment analysis of differentially expressed genes in chronic heart failure

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Xiaoli Fang ◽  
Xue Zeng ◽  
Miao Wang ◽  
Liuqiong Qin ◽  
Chuanhui Tan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed

scholarly journals bcbioRNASeq: R package for bcbio RNA-seq analysis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1976 ◽  
Author(s):  
Michael J. Steinbaugh ◽  
Lorena Pantano ◽  
Rory D. Kirchner ◽  
Victor Barrera ◽  
Brad A. Chapman ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
R Package ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Control Analysis ◽  
Rna Seq ◽  
Sequencing Data ◽  
Post Process

RNA-seq analysis involves multiple steps from processing raw sequencing data to identifying, organizing, annotating, and reporting differentially expressed genes. bcbio is an open source, community-maintained framework providing automated and scalable RNA-seq methods for identifying gene abundance counts. We have developed bcbioRNASeq, a Bioconductor package that provides ready-to-render templates and wrapper functions to post-process bcbio output data. bcbioRNASeq automates the generation of high-level RNA-seq reports, including identification of differentially expressed genes, functional enrichment analysis and quality control analysis.

scholarly journals RNA-Seq Analysis Reveals Candidate Targets for Curcumin againstTetranychus cinnabarinus

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xuejiao Liu ◽  
Dousheng Wu ◽  
Yongqiang Zhang ◽  
Hong Zhou ◽  
Ting Lai ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Reference Sequence ◽  
Broad Host Range ◽  
Rna Seq ◽  
Dominant Group ◽  
Curcumin Treatment ◽  
Transcriptional Changes ◽  
Or Genes

Tetranychus cinnabarinusis an important agricultural pest with a broad host range. We previously identified curcumin as a promising acaricidal compound againstT. cinnabarinus. However, the acaricidal mechanism of curcumin remains unknown. In this study, RNA-seq was employed to analyze the transcriptome changes inT. cinnabarinustreated with curcumin or the solvent. A total of 105,706,297 clean sequence reads were generated by sequencing, with more than 90% of the reads successfully mapped to the reference sequence. The RNA-seq identified 111 and 96 differentially expressed genes between curcumin- and solvent-treated mites at 24 and 48 h after treatment, respectively. GO enrichment analysis of differentially expressed genes showed that the cellular process was the dominant group at both time points. Finally, we screened 23 differentially expressed genes that were functionally identical or similar to the targets of common insecticide/acaricides or genes that were associated with mite detoxification and metabolism. Calmodulin, phospholipase A2, and phospholipase C were activated upon curcumin treatment suggesting that the calcium channel related genes might play important roles in mite’s response to curcumin. Overall our results revealed the global transcriptional changes inT. cinnabarinusafter curcumin treatment to enable further identification of the targets of curcumin in mites.

Transcriptional identification of differentially expressed genes during the prepupal–pupal transition in the oriental armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae)

2021 ◽  
pp. 1-14
Author(s):  
Peirong Li ◽  
Xinru Li ◽  
Wei Wang ◽  
Xiaoling Tan ◽  
Xiaoqi Wang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Metabolic Pathways ◽  
Developmental Stages ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Mythimna Separata ◽  
Kegg Pathway Analysis ◽  
Oriental Armyworm ◽  
Lepidoptera Noctuidae

Abstract The oriental armyworm, Mythimna separata (Walker) is a serious pest of agriculture that does particular damage to Gramineae crops in Asia, Europe, and Oceania. Metamorphosis is a key developmental stage in insects, although the genes underlying the metamorphic transition in M. separata remain largely unknown. Here, we sequenced the transcriptomes of five stages; mature larvae (ML), wandering (W), and pupation (1, 5, and 10 days after pupation, designated P1, P5, and P10) to identify transition-associated genes. Four libraries were generated, with 22,884, 23,534, 26,643, and 33,238 differentially expressed genes (DEGs) for the ML-vs-W, W-vs-P1, P1-vs-P5, and P5-vs-P10, respectively. Gene ontology enrichment analysis of DEGs showed that genes regulating the biosynthesis of the membrane and integral components of the membrane, which includes the cuticular protein (CP), 20-hydroxyecdysone (20E), and juvenile hormone (JH) biosynthesis, were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs were enriched in the metabolic pathways. Of these DEGs, thirty CP, seventeen 20E, and seven JH genes were differentially expressed across the developmental stages. For transcriptome validation, ten CP, 20E, and JH-related genes were selected and verified by real-time PCR quantitative. Collectively, our results provided a basis for further studies of the molecular mechanism of metamorphosis in M. separata.

scholarly journals Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Yuan ◽  
Shenqiang Hu ◽  
Liang Li ◽  
Chunchun Han ◽  
Hehe Liu ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Lipid Droplets ◽  
Cell Model ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Follicle Development ◽  
Microscopy Analysis ◽  
Stearoyl Coa Desaturase ◽  
Underlying Mechanisms

Abstract Background Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Results Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. Conclusions This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.

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