Prediction of genetic risk factors of atherosclerosis using various bioinformatic tools

Wang, H.X.; Zhao, Yanxia

doi:10.4238/gmr.15027347

Cited by 9 publications

(8 citation statements)

References 29 publications

(28 reference statements)

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“…These will define gene networks as structural pathways or molecular functions specific for that condition. GO analysis on ATH‐DEGs has showed an enrichment in proteins related to nucleic acid function, such as epigenetic regulators [245], [liver X] nuclear receptors [246], or ribosomal proteins [247], while our own GO analysis on a subset of miRNA targets obtained after an integrated analysis in ATH also showed an enrichment in genes related to the function of nucleic acids (Hueso et al, manuscript in preparation).…”

Section: Unveiling Rna: Rna Regulatory Network In the Progression Ofmentioning

confidence: 96%

Unveiling ncRNA regulatory axes in atherosclerosis progression

Navarro

Mallén

Cruzado

et al. 2020

Clinical & Translational Med

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Completion of the human genome sequencing project highlighted the richness of the cellular RNA world, and opened the door to the discovery of a plethora of short and long non‐coding RNAs (the dark transcriptome) with regulatory or structural potential, which shifted the balance of pathological gene alterations from coding to non‐coding RNAs. Thus, disease risk assessment currently has to also evaluate the expression of new RNAs such as small micro RNAs (miRNAs), long non‐coding RNAs (lncRNAs), circular RNAs (circRNAs), competing endogenous RNAs (ceRNAs), retrogressed elements, 3′UTRs of mRNAs, etc. We are interested in the pathogenic mechanisms of atherosclerosis (ATH) progression in patients suffering Chronic Kidney Disease, and in this review, we will focus in the role of the dark transcriptome (non‐coding RNAs) in ATH progression. We will focus in miRNAs and in the formation of regulatory axes or networks with their mRNA targets and with the lncRNAs that function as miRNA sponges or competitive inhibitors of miRNA activity. In this sense, we will pay special attention to retrogressed genomic elements, such as processed pseudogenes and Alu repeated elements, that have been recently seen to also function as miRNA sponges, as well as to the use or miRNA derivatives in gene silencing, anti‐ATH therapies. Along the review, we will discuss technical developments associated to research in lncRNAs, from sequencing technologies to databases, repositories and algorithms to predict miRNA targets, as well as new approaches to miRNA function, such as integrative or enrichment analysis and their potential to unveil RNA regulatory networks.

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Section: Unveiling Rna: Rna Regulatory Network In the Progression Ofmentioning

confidence: 96%

Unveiling ncRNA regulatory axes in atherosclerosis progression

Navarro

Mallén

Cruzado

et al. 2020

Clinical & Translational Med

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“…Results of GO analysis of the gene enrichment in these datasets showed that the VTE-associated DEGs were signi cantly enriched in RNA catabolic process. Wang, HX found previously that RPL9, RPL35, and RPS7 were hub genes in the PPI network of GSE13985, which was used to identify potential markers of atherosclerosis development [36]. Interestingly, a study from Mi, YH reported that the major risk factors for atherothrombotic disease were also signi cantly associated with VTE, which contributes to the explanation of why atherosclerosis is an independent risk factor for VTE [37].…”

Section: Discussionmentioning

confidence: 96%

Integrated Transcriptome-wide Profiling and Protein Structure Analysis of Pathogenic Genes in Venous Thromboembolism

Ding

Zhang²,

Cao³

2021

Preprint

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BackgroundGenetic factors are considered to determine the balance of the coagulation and anticoagulation processes, yet the genetic variants related to venous thromboembolism (VTE) remain unclear. This study aimed to investigate the potential molecular mechanisms and pathogenic mutations associated with VTE by determining VTE-related differentially expressed genes (DEGs) by transcriptome-wide profiling and assaying protein structure in VTE.MethodsTwo gene expression datasets, GSE48000 and GSE19151, were accessed from the Gene Expression Omnibus (GEO) database to obtain gene expression data associated with VTE. We identified the DEGs between VTE patients and healthy people using R and performed functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, whole-exome sequencing (WES) was performed for 25 VTE patients and 17 normal cases, and the structural locations of pathogenic missense mutations were identified using pyMOL. Finally, DGIdb database was used to select candidate drugs for the treatment of VTE.ResultsA total of 232 DEGs were identified from the GEO database. The significant function of these DEGs was mostly involved in RNA catabolic process and ribosome pathway. Notably, the results of WES for DEGs and protein structure analysis showed that Histamine N-Methyltransferase (HNMT) (chr2: 138759649 C>T, rs11558538) may be a main predisposing factor for VTE. In addition, Amodiaquine, Harmaline, Aspirin, Metoprine, Dabigatran, and Diphenhydramine were screened for VTE therapy.ConclusionThe results showed that HNMT (chr2: 138759649 C>T, rs11558538) may be potential target for the diagnosis and treatment of VTE.

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“…Although the study mentioned that these genes are downregulated in the FH patient’s blood cells, they are significantly upregulated in the reported dataset. In addition, they claimed that cytochrome-c oxidase genes could contribute to atherosclerosis development, yet there was no substantial evidence provided ( Wang and Zhao, 2016 ). The study conducted by Smolock et al (2012) suggested that RPL17 acts as an inhibitor for vascular smooth muscle cells (VSMC) and might be a therapeutic target to limit the thickening of carotid intima ( Smolock et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Differentially Expressed Genes and Molecular Pathways in Familial Hypercholesterolemia Involved in Atherosclerosis: A Systematic and Bioinformatics Approach

Kumar

Bithia

et al. 2020

Front. Genet.

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Background and Aims: Familial hypercholesterolemia (FH) is one of the major risk factor for the progression of atherosclerosis and coronary artery disease. This study focused on identifying the dysregulated molecular pathways and core genes that are differentially regulated in FH and to identify the possible genetic factors and potential underlying mechanisms that increase the risk to atherosclerosis in patients with FH. Methods: The Affymetrix microarray dataset (GSE13985) from the GEO database and the GEO2R statistical tool were used to identify the differentially expressed genes (DEGs) from the white blood cells (WBCs) of five heterozygous FH patients and five healthy controls. The interaction between the DEGs was identified by applying the STRING tool and visualized using Cytoscape software. MCODE was used to determine the gene cluster in the interactive networks. The identified DEGs were subjected to the DAVID v6.8 webserver and ClueGo/CluePedia for functional annotation, such as gene ontology (GO) and enriched molecular pathway analysis of DEGs. Results: We investigated the top 250 significant DEGs ( p -value < 0.05; fold two change ≥ 1 or ≤ −1). The GO analysis of DEGs with significant differences revealed that they are involved in critical biological processes and molecular pathways, such as myeloid cell differentiation, peptidyl-lysine modification, signaling pathway of MyD88-dependent Toll-like receptor, and cell-cell adhesion. The analysis of enriched KEGG pathways revealed the association of the DEGs in ubiquitin-mediated proteolysis and cardiac muscle contraction. The genes involved in the molecular pathways were shown to be differentially regulated by either activating or inhibiting the genes that are essential for the canonical signaling pathways. Our study identified seven core genes ( UQCR11, UBE2N, ADD1, TLN1, IRAK3, LY96 , and MAP3K1 ) that are strongly linked to FH and lead to a higher risk of atherosclerosis. Conclusion: We identified seven core genes that represent potential molecular biomarkers for the diagnosis of atherosclerosis and might serve as a platform for developing therapeutics against both FH and atherosclerosis. However, functional studies are further needed to validate their role in the pathogenesis of FH and atherosclerosis.

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Prediction of genetic risk factors of atherosclerosis using various bioinformatic tools

Cited by 9 publications

References 29 publications

Unveiling ncRNA regulatory axes in atherosclerosis progression

Unveiling ncRNA regulatory axes in atherosclerosis progression

Integrated Transcriptome-wide Profiling and Protein Structure Analysis of Pathogenic Genes in Venous Thromboembolism

Analysis of Differentially Expressed Genes and Molecular Pathways in Familial Hypercholesterolemia Involved in Atherosclerosis: A Systematic and Bioinformatics Approach

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