scholarly journals Genome regulation and gene interaction networks inferred from muscle transcriptome underlying feed efficiency in Pigs

Author(s):  
Victor AO. Carmelo ◽  
Haja N. Kadarmideen

AbstractImprovement of feed efficiency (FE) is key for sustainability and cost reduction in pig production. Our aim was to characterize the muscle transcriptomic profiles in Danbred Duroc (Duroc) and Danbred Landrace (Landrace), in relation to FE for identifying potential biomarkers. RNA-seq data was analyzed employing differential gene expression methods, gene-gene interaction and network analysis, including pathway and functional analysis. We compared the results with genome regulation in human exercise data. In the differential expression analysis, 13 genes were differentially expressed, including: MRPS11, MTRF1, TRIM63, MGAT4A, KLH30. Based on a novel gene selection method, the divergent count, we performed pathway enrichment analysis. We found 5 significantly enriched pathways related to feed conversion ratio (FCR). These pathways were mainly mitochondrial, and summarized in the mitochondrial translation elongation (MTR) pathway. In the gene interaction analysis, highlights include the mitochondrial genes: PPIF, MRPL35, NDUFS4and the fat metabolism and obesity genes: AACS, SMPDL3B, CTNNBL1, NDUFS4 and LIMD2. In the network analysis, we identified two modules significantly correlated with FCR. Pathway enrichment of modules identified MTR, electron transport chain and DNA repair as enriched pathways. In the network analysis, the mitochondrial gene group NDUF was a key hub group, showing potential as biomarkers. Comparing with human transcriptomic exercise studies, genes related to exercise displayed enrichment in our FCR related genes. We conclude that mitochondrial activity is a driver for FCR in muscle tissue, and mitochondrial genes could be potential biomarkers for FCR in pigs. We hypothesize that increased FE mimics processes triggered in exercised muscle.

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinghong Shi ◽  
Hanxin Yao

Abstract Background Our study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis. Methods Expression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD). Results In total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1). Conclusion The identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.


Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 114
Author(s):  
Anastasia N. Vaganova ◽  
Savelii R. Kuvarzin ◽  
Anastasia M. Sycheva ◽  
Raul R. Gainetdinov

Trace amine-associated receptors (TAARs) interact with amine compounds called “trace amines” which are present in tissues at low concentrations. Recently, TAARs expression in neoplastic tumors was reported. In this study, TAARs expression was analyzed in public RNAseq datasets in nevi and melanoma samples and compared to the expression of dopamine receptors (DRDs) that are known to be involved in melanoma pathogenesis. It was found that all DRDs and TAARs are expressed in nevi at comparable levels. Differential expression analysis demonstrated the drastic decrease of TAAR1, TAAR2, TAAR5, TAAR6, and TAAR8 expression in melanomas compared to benign nevi with only TAAR6, TAAR8, and TAAR9 remaining detectable in malignant tumors. No association of TAARs expression levels and melanoma clinicopathological characteristics was observed. TAARs co-expressed genes in melanoma and nevi were selected by correlation values for comparative pathway enrichment analysis between malignant and benign neoplasia. It was found that coexpression of TAARs with genes inquired in neurotransmitter signaling is lost in melanoma, and tumor-specific association of TAAR6 expression with the mTOR pathway and inflammatory signaling is observed. It is not excluded that TAARs may have certain functions in melanoma pathogenesis, the significance of which to tumor progression is yet to be understood.


2020 ◽  
Vol 8 (1) ◽  
pp. e001126
Author(s):  
Catherine E Cioffi ◽  
K M Venkat Narayan ◽  
Ken Liu ◽  
Karan Uppal ◽  
Dean P Jones ◽  
...  

IntroductionBody fat distribution is strongly associated with cardiometabolic disease (CMD), but the relative importance of hepatic fat as an underlying driver remains unclear. Here, we applied a systems biology approach to compare the clinical and molecular subnetworks that correlate with hepatic fat, visceral fat, and abdominal subcutaneous fat distribution.Research design and methodsThis was a cross-sectional sub-study of 283 children/adolescents (7–19 years) from the Yale Pediatric NAFLD Cohort. Untargeted, high-resolution metabolomics (HRM) was performed on plasma and combined with existing clinical variables including hepatic and abdominal fat measured by MRI. Integrative network analysis was coupled with pathway enrichment analysis and multivariable linear regression (MLR) to examine which metabolites and clinical variables associated with each fat depot.ResultsThe data divided into four communities of correlated variables (|r|>0.15, p<0.05) after integrative network analysis. In the largest community, hepatic fat was associated with eight clinical biomarkers, including measures of insulin resistance and dyslipidemia, and 878 metabolite features that were enriched predominantly in amino acid (AA) and lipid pathways in pathway enrichment analysis (p<0.05). Key metabolites associated with hepatic fat included branched-chain AAs (valine and isoleucine/leucine), aromatic AAs (tyrosine and tryptophan), serine, glycine, alanine, and pyruvate, as well as several acylcarnitines and glycerophospholipids (all q<0.05 in MLR adjusted for covariates). The other communities detected in integrative network analysis consisted of abdominal visceral, superficial subcutaneous, and deep subcutaneous fats, but no clinical variables, fewer metabolite features (280, 312, and 74, respectively), and limited findings in pathway analysis.ConclusionsThese data-driven findings show a stronger association of hepatic fat with key CMD risk factors compared with abdominal fats. The molecular network identified using HRM that associated with hepatic fat provides insight into potential mechanisms underlying the hepatic fat–insulin resistance interface in youth.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Farhadian ◽  
Seyed Abbas Rafat ◽  
Bahman Panahi ◽  
Christopher Mayack

AbstractThe exponential growth in knowledge has resulted in a better understanding of the lactation process in a wide variety of animals. However, the underlying genetic mechanisms are not yet clearly known. In order to identify the mechanisms involved in the lactation process, various mehods, including meta-analysis, weighted gene co-express network analysis (WGCNA), hub genes identification, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment at before peak (BP), peak (P), and after peak (AP) stages of the lactation processes have been employed. A total of 104, 85, and 26 differentially expressed genes were identified based on PB vs. P, BP vs. AP, and P vs. AP comparisons, respectively. GO and KEGG pathway enrichment analysis revealed that DEGs were significantly enriched in the “ubiquitin-dependent ERAD” and the “chaperone cofactor-dependent protein refolding” in BP vs. P and P vs. P, respectively. WGCNA identified five significant functional modules related to the lactation process. Moreover, GJA1, AP2A2, and NPAS3 were defined as hub genes in the identified modules, highlighting the importance of their regulatory impacts on the lactation process. The findings of this study provide new insights into the complex regulatory networks of the lactation process at three distinct stages, while suggesting several candidate genes that may be useful for future animal breeding programs. Furthermore, this study supports the notion that in combination with a meta-analysis, the WGCNA represents an opportunity to achieve a higher resolution analysis that can better predict the most important functional genes that might provide a more robust bio-signature for phenotypic traits, thus providing more suitable biomarker candidates for future studies.


2021 ◽  
Vol 17 (6) ◽  
pp. e1008979
Author(s):  
Michael Hellstern ◽  
Jing Ma ◽  
Kun Yue ◽  
Ali Shojaie

Existing software tools for topology-based pathway enrichment analysis are either computationally inefficient, have undesirable statistical power, or require expert knowledge to leverage the methods’ capabilities. To address these limitations, we have overhauled NetGSA, an existing topology-based method, to provide a computationally-efficient user-friendly tool that offers interactive visualization. Pathway enrichment analysis for thousands of genes can be performed in minutes on a personal computer without sacrificing statistical power. The new software also removes the need for expert knowledge by directly curating gene-gene interaction information from multiple external databases. Lastly, by utilizing the capabilities of Cytoscape, the new software also offers interactive and intuitive network visualization.


2020 ◽  
Author(s):  
Guona Li ◽  
Mengmeng Kang ◽  
Siyuan Sheng ◽  
Ziyi Chen ◽  
Kunshan Li ◽  
...  

Abstract Background: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. It is crucial to screen potential biomarkers for the diagnosis, pathogenesis, and prognosis of CRC because there are limited clinical symptoms associated with this cancer. Therefore, we attempted to identify biomarkers associated with the occurrence and progression of CRC by utilizing bioinformatic analysis and to elucidate a molecular mechanism for the diagnosis and treatment of CRC. Methods: Two independent gene expression profile datasets of colonic neoplasms (GSE44076 and GSE37182) were collected from public GEO datasets, which included 182 tumor tissues and 236 normal tissues. Next, differentially expressed genes (DEGs) between CRC colonic samples and non-CRC colonic samples were obtained via GEO2R online tools. Subsequently, hub genes were selected by several analyses of DEGs, including GO pathway enrichment analysis, KEGG pathway enrichment analysis, and PPI network analysis. Finally, the correlation between the hub genes and the occurrence of CRC was tested by harnessing survival analysis and ROC curve analysis. Results: Sixty-one shared DEGs were screened, including 44 high-expression genes and 17 low-expression genes, in CRC samples. Four genes (MYC, TIMP1, MMP7, and COL1A1) were considered to be hub genes because they exhibited higher connectivity degree scores through PPI network analysis. More importantly, there was a significant correlation between increased expression of TIMP1 and reduced survival time in patients with colorectal cancer. Conclusion: By using bioinformatic analysis, this study suggested that Timp-1 may represent a potential biomarker for the diagnosis and prognosis of targeted molecular therapy for CRC.


2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.


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