scholarly journals The Genetic Dissection of Ace2 Expression Variation in the Heart of Murine Genetic Reference Population

2020 ◽  
Vol 7 ◽  
Author(s):  
Fuyi Xu ◽  
Jun Gao ◽  
Undral Munkhsaikhan ◽  
Ning Li ◽  
Qingqing Gu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Reference Population ◽  
Functional Enrichment ◽  
P Wave ◽  
Eqtl Mapping ◽  
Cardiac Damage ◽  
Wide Range ◽  
Cardiovascular Traits

Background: A high inflammatory and cytokine burden that induces vascular inflammation, myocarditis, cardiac arrhythmias, and myocardial injury is associated with a lethal outcome in COVID-19. The SARS-CoV-2 virus utilizes the ACE2 receptor for cell entry in a similar way to SARS-CoV. This study investigates the regulation, gene network, and associated pathways of ACE2 that may be involved in inflammatory and cardiovascular complications of COVID-19.Methods: Cardiovascular traits were determined in the one of the largest mouse genetic reference populations: BXD recombinant inbred strains using blood pressure, electrocardiography, and echocardiography measurements. Expression quantitative trait locus (eQTL) mapping, genetic correlation, and functional enrichment analysis were used to identify Ace2 regulation, gene pathway, and co-expression networks.Results: A wide range of variation was found in expression of Ace2 among the BXD strains. Levels of Ace2 expression are negatively correlated with cardiovascular traits, including systolic and diastolic blood pressure and P wave duration and amplitude. Ace2 co-expressed genes are significantly involved in cardiac- and inflammatory-related pathways. The eQTL mapping revealed that Cyld is a candidate upstream regulator for Ace2. Moreover, the protein–protein interaction (PPI) network analysis inferred several potential key regulators (Cul3, Atf2, Vcp, Jun, Ppp1cc, Npm1, Mapk8, Set, Dlg1, Mapk14, and Hspa1b) for Ace2 co-expressed genes in the heart.Conclusions:Ace2 is associated with blood pressure, atrial morphology, and sinoatrial conduction in BXD mice. Ace2 co-varies with Atf2, Cyld, Jun, Mapk8, and Mapk14 and is enriched in the RAS, TGFβ, TNFα, and p38α signaling pathways, involved in inflammation and cardiac damage. We suggest that all these novel Ace2-associated genes and pathways may be targeted for preventive, diagnostic, and therapeutic purposes in cardiovascular damage in patients with systemic inflammation, including COVID-19 patients.

scholarly journals Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1247
Author(s):  
Anna Ulrich ◽  
Pablo Otero-Núñez ◽  
John Wharton ◽  
Emilia M. Swietlik ◽  
Stefan Gräf ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Quantitative Trait ◽  
Association Studies ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Population Based ◽  
Functional Enrichment ◽  
Eqtl Mapping ◽  
Pulmonary Arterial

Expression quantitative trait loci (eQTL) can provide a link between disease susceptibility variants discovered by genetic association studies and biology. To date, eQTL mapping studies have been primarily conducted in healthy individuals from population-based cohorts. Genetic effects have been known to be context-specific and vary with changing environmental stimuli. We conducted a transcriptome- and genome-wide eQTL mapping study in a cohort of patients with idiopathic or heritable pulmonary arterial hypertension (PAH) using RNA sequencing (RNAseq) data from whole blood. We sought confirmation from three published population-based eQTL studies, including the GTEx Project, and followed up potentially novel eQTL not observed in the general population. In total, we identified 2314 eQTL of which 90% were cis-acting and 75% were confirmed by at least one of the published studies. While we observed a higher GWAS trait colocalization rate among confirmed eQTL, colocalisation rate of novel eQTL reported for lung-related phenotypes was twice as high as that of confirmed eQTL. Functional enrichment analysis of genes with novel eQTL in PAH highlighted immune-related processes, a suspected contributor to PAH. These potentially novel eQTL specific to or active in PAH could be useful in understanding genetic risk factors for other diseases that share common mechanisms with PAH.

MIMPFC: Identifying miRNA–mRNA regulatory modules by combining phase-only correlation and improved rough-fuzzy clustering

2018 ◽  
Vol 16 (01) ◽  
pp. 1750028
Author(s):  
Dan Luo ◽  
Shu-Lin Wang ◽  
Jianwen Fang ◽  
Wei Zhang
Keyword(s):  
Fuzzy Clustering ◽  
Biological Significance ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Computational Method ◽  
Functional Enrichment ◽  
Regulatory Relationship ◽  
Regulatory Modules ◽  
Wide Range ◽  
Highly Correlated

MicroRNAs (miRNAs) play a key role in gene expression and regulation in various organisms. They control a wide range of biological processes and are involved in several types of cancers by causing mRNA degradation or translational inhibition. However, the functions of most miRNAs and their precise regulatory mechanisms remain elusive. With the accumulation of the expression data of miRNAs and mRNAs, many computational methods have been proposed to predict miRNA–mRNA regulatory relationship. However, most existing methods require the number of modules predefined that may be difficult to determine beforehand. Here, we propose a novel computational method to discover miRNA–mRNA regulatory modules by combining Phase-only correlation and improved rough-Fuzzy Clustering (MIMPFC). The proposed method is evaluated on three heterogeneous datasets, and the obtained results are further validated through relevant literatures, biological significance and functional enrichment analysis. The analysis results show that the identified modules are highly correlated with the biological conditions. A large part of the regulatory relationships found by MIMPFC has been confirmed in the experimentally verified databases. It demonstrates that the modules found by MIMPFC are biologically significant.

scholarly journals Understanding the Modus Operandi of MicroRNA Regulatory Clusters

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1103 ◽  
Author(s):  
Arthur C. Oliveira ◽  
Luiz A. Bovolenta ◽  
Lucas Alves ◽  
Lucas Figueiredo ◽  
Amanda O. Ribeiro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Modus Operandi ◽  
Wide Range

MicroRNAs (miRNAs) are non-coding RNAs that regulate a wide range of biological pathways by post-transcriptionally modulating gene expression levels. Given that even a single miRNA may simultaneously control several genes enrolled in multiple biological functions, one would expect that these tiny RNAs have the ability to properly sort among distinctive cellular processes to drive protein production. To test this hypothesis, we scrutinized previously published microarray datasets and clustered protein-coding gene expression profiles according to the intensity of fold-change levels caused by the exogenous transfection of 10 miRNAs (miR-1, miR-7, miR-9, miR-124, miR-128a, miR-132, miR-133a, miR-142, miR-148b, miR-181a) in a human cell line. Through an in silico functional enrichment analysis, we discovered non-randomic regulatory patterns, proper of each cluster identified. We demonstrated that miRNAs are capable of equivalently modulate the expression signatures of target genes in regulatory clusters according to the biological function they are assigned to. Moreover, target prediction analysis applied to ten vertebrate species, suggest that such miRNA regulatory modus operandi is evolutionarily conserved within vertebrates. Overall, we discovered a complex regulatory cluster-module strategy driven by miRNAs, which relies on the controlled intensity of the repression over distinct targets under specific biological contexts. Our discovery helps to clarify the mechanisms underlying the functional activity of miRNAs and makes it easier to take the fastest and most accurate path in the search for the functions of miRNAs in any distinct biological process of interest.

scholarly journals Co-expression networks uncover regulation of splicing and transcription markers of disease

10.29007/rl4h ◽  
2020 ◽  
Author(s):  
Pan Zhang ◽  
Bruce Southey ◽  
Sandra Rodriguez-Zas
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Transcriptional Networks ◽  
Substantial Impact ◽  
Wide Range ◽  
Or Gene ◽  
Significant Patterns

Gene co-expression networks based on gene expression data are usually used to capture biologically significant patterns, enabling the discovery of biomarkers and interpretation of regulatory relationships. However, the coordination of numerous splicing changes within and across genes can exert a substantial impact on the function of these genes. This is particularly impactful in studies of the properties of the nervous system, which can be masked in the networks that only assess the correlation between gene expression levels. A bioinformatics approach was developed to uncover the role of alternative splicing and associated transcriptional networks using RNA-seq profiles. Data from 40 samples, including control and two treatments associated with sensitivity to stimuli across two central nervous system regions that can present differential splicing, were explored. The gene expression and relative isoform levels were integrated into a transcriptome-wide matrix, and then Graphical Lasso was applied to capture the interactions between genes and isoforms. Next, functional enrichment analysis enabled the discovery of pathways dysregulated at the isoform or gene levels and the interpretation of these interactions within a central nervous region. In addition, a Bayesian biclustering strategy was used to reconstruct treatment-specific networks from gene expression profile, allowing the identification of hub molecules and visualization of highly connected modules of isoforms and genes in specific conditions. Our bioinformatics approach can offer comparable insights into the discovery of biomarkers and therapeutic targets for a wide range of diseases and conditions.

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

scholarly journals Structural variations in papaya genomes

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenyang Liao ◽  
Xunxiao Zhang ◽  
Shengcheng Zhang ◽  
Zhicong Lin ◽  
Xingtan Zhang ◽  
...  
Keyword(s):  
Agronomic Traits ◽  
Enrichment Analysis ◽  
Copy Number Variant ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Structural Variations ◽  
Reproduction Traits ◽  
Depth Study ◽  
Environmental Adaptability ◽  
The Impact

Abstract Background Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers. Results We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress. Conclusions SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.

scholarly journals CCTs as new biomarkers for the prognosis of head and neck squamous cancer

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu
Keyword(s):  
Head And Neck ◽  
Survival Data ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Advanced Tumor Stage ◽  
Expression Levels ◽  
T Complex ◽  
Advanced Tumor ◽  
Squamous Cancer

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

scholarly journals Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

2021 ◽  
Vol 28 (1) ◽  
pp. 20-33
Author(s):  
Lydia-Eirini Giannakou ◽  
Athanasios-Stefanos Giannopoulos ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
Erasmia Rouka ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Respiratory Pathogens ◽  
Gram Negative ◽  
Human Proteins ◽  
Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

scholarly journals Isolation and identification of a novel bacterium, Pseudomonas sp. ZyL-01, involved in the biodegradation of CL-20

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhiyong Liu ◽  
Kai Dang ◽  
Cunzhi Li ◽  
Junhong Gao ◽  
Hong Wang ◽  
...  
Keyword(s):  
Microbial Community ◽  
Environmental Fate ◽  
Draft Genome ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Community Diversity ◽  
Functional Enrichment ◽  
Metagenomic Sequencing ◽  
Isolation And Identification ◽  
Novel Bacterium

Abstract Hexanitrohexaazaisowurtzitane (CL-20) is a compound with a polycyclic cage and an N-nitro group that has been shown to play an unfavorable role in environmental fate, biosafety, and physical health. The aim of this study was to isolate the microbial community and to identify a single microbial strain that can degrade CL-20 with desirable efficiency. Metagenomic sequencing methods were performed to investigate the dynamic changes in the composition of the community diversity. The most varied genus among the microbial community was Pseudomonas, which increased from 1.46% to 44.63% during the period of incubation (MC0–MC4). Furthermore, the new strain was isolated and identified from the activated sludge by bacterial morphological and 16s rRNA sequencing analyses. The CL-20 concentrations decreased by 75.21 μg/mL and 74.02 μg/mL in 48 h by MC4 and Pseudomonas sp. ZyL-01, respectively. Moreover, ZyL-01 could decompose 98% CL-20 of the real effluent in 14 day’s incubation with the glucose as carbon source. Finally, a draft genome sequence was obtained to predict possible degrading enzymes involved in the biodegradation of CL-20. Specifically, 330 genes that are involved in energy production and conversion were annotated by Gene Ontology functional enrichment analysis, and some of these candidates may encode enzymes that are responsible for CL-20 degradation. In summary, our studies indicate that microbes might be a valuable biological resource for the treatment of environmental contamination caused by CL-20 and that Pseudomonas sp. ZyL-01 might be a promising candidate for eradicating CL-20 to achieve a more biosafe environment and improve public health.

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