scholarly journals Dissecting the Pathogenesis of Diabetic Retinopathy Based on the Biological ceRNA Network and Genome Variation Disturbance

2021 ◽  
Vol 2021 ◽  
pp. 1-29
Author(s):  
Xiaodan Zhu ◽  
Ming Hao ◽  
Xinyang Yu ◽  
Wenjian Lin ◽  
Xuefei Ma ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Biological Networks ◽  
Genomic Variation ◽  
Diabetic Microangiopathy ◽  
Complex Nature ◽  
Regulatory Relationship ◽  
Expression Variation ◽  
Genomic Variations ◽  
Cerna Network ◽  
Target Binding

Background. Diabetic retinopathy (DR) is the most important manifestation of diabetic microangiopathy. It is essential to explore the gene regulatory relationship and genomic variation disturbance of biological networks in DR progression. Methods. In this study, we constructed a comprehensive lncRNA-mRNA ceRNA network of DR procession (CLMN) and explored its topological characteristics. Results. Modular and functional analysis indicated that the organization of CLMN performed fundamental and specific functions in diabetes and DR pathology. The differential expression of hub ceRNA nodes and positive correlation reveals the highly connected ceRNA regulation and important roles in the regulating of DR pathology. A large proportion of SNPs in the TFBS, DHS, and enhancer regions of lncRNAs will affect lncRNA transcription and further cause expression variation. Some SNPs were found to disrupt the lncRNA functional elements such as miRNA target binding sites. These results indicate the complex nature of genotypic effects in the disturbing of CLMN and further contribute to gene expression variation and different disease phenotypes. Conclusion. The identification of individual genomic variations and analysis of biological network disturbance by these genomic variations will help provide more personalized treatment plans and promote the development of precision medicine for DR.

Algorithmic and Stochastic Representations of Gene Regulatory Networks and Protein-Protein Interactions

2019 ◽  
Vol 19 (6) ◽  
pp. 413-425 ◽  
Author(s):  
Athanasios Alexiou ◽  
Stylianos Chatzichronis ◽  
Asma Perveen ◽  
Abdul Hafeez ◽  
Ghulam Md. Ashraf
Keyword(s):  
Protein Interactions ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Review Paper ◽  
Boolean Networks ◽  
Diagnostic Tools ◽  
Complex Nature ◽  
Cellular Interactions ◽  
Protein Protein Interactions ◽  
Deterministic Models

Background:Latest studies reveal the importance of Protein-Protein interactions on physiologic functions and biological structures. Several stochastic and algorithmic methods have been published until now, for the modeling of the complex nature of the biological systems.Objective:Biological Networks computational modeling is still a challenging task. The formulation of the complex cellular interactions is a research field of great interest. In this review paper, several computational methods for the modeling of GRN and PPI are presented analytically.Methods:Several well-known GRN and PPI models are presented and discussed in this review study such as: Graphs representation, Boolean Networks, Generalized Logical Networks, Bayesian Networks, Relevance Networks, Graphical Gaussian models, Weight Matrices, Reverse Engineering Approach, Evolutionary Algorithms, Forward Modeling Approach, Deterministic models, Static models, Hybrid models, Stochastic models, Petri Nets, BioAmbients calculus and Differential Equations.Results:GRN and PPI methods have been already applied in various clinical processes with potential positive results, establishing promising diagnostic tools.Conclusion:In literature many stochastic algorithms are focused in the simulation, analysis and visualization of the various biological networks and their dynamics interactions, which are referred and described in depth in this review paper.

scholarly journals Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001189
Author(s):  
Yoshitaka Hashimoto ◽  
Masahide Hamaguchi ◽  
Ayumi Kaji ◽  
Ryosuke Sakai ◽  
Noriyuki Kitagawa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Liver Fibrosis ◽  
Proliferative Diabetic Retinopathy ◽  
Binding Protein ◽  
Protein Glycosylation ◽  
Diabetic Microangiopathy ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

IntroductionNon-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people with type 2 diabetes. The purpose of this cross-sectional study was to investigate the association between serum mac-2 binding protein glycosylation isomer (M2BPGi) levels and diabetic complications in people with type 2 diabetes.Research design and methodsSerum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normoalbuminuria, microalbuminuria, or macroalbuminuria. Retinopathy was divided into three groups: no-diabetic retinopathy (NoDR), non-proliferative-diabetic retinopathy (NPDR), or proliferative-diabetic retinopathy (PDR) .ResultsThe mean age for the 363 studied subjects (212 males) was 66.4±10.6 years, the median serum M2BPGi level was 0.77 (0.57–1.04) C.O.I., and the median UAE was 22 (9–82.1) mg/g creatinine. M2BPGi levels in microalbuminuria (0.83 (0.61 to 1.18) C.O.I.) and macroalbuminuria (0.88 (0.67 to 1.22) C.O.I.) cases were higher than those in normoalbuminuria cases (0.71 (0.54 to 0.92) C.O.I.). M2BPGi levels in NPDR (0.93 (0.68 to 1.28) C.O.I.) and PDR (0.95 (0.71 to 1.31) C.O.I.) cases were higher than in cases with NoDR (0.73 (0.56 to 0.99) C.O.I.). Furthermore, M2BPGi levels in subjects with a history of cardiovascular diseases were higher than in those with no such history (0.82 (0.65 to 1.22) vs 0.76 (0.55 to 1.03) C.O.I., p=0.019). The logarithm of (M2BPGi+1) was associated with the logarithm of UAE values after adjusting for covariates (standardized β=0.107, p=0.031).ConclusionsThis study reveals a close association between serum M2BPGi levels and diabetic microangiopathy and macroangiopathy in people with type 2 diabetes. The results also show that liver fibrosis, evaluated by M2BPGi, is independently associated with an increased risk of albuminuria.

scholarly journals LnCeVar: a comprehensive database of genomic variations that disturb ceRNA network regulation

2019 ◽  
Author(s):  
Peng Wang ◽  
Xin Li ◽  
Yue Gao ◽  
Qiuyan Guo ◽  
Shangwei Ning ◽  
...  
Keyword(s):  
Cox Regression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Data Sets ◽  
Genomic Variations ◽  
Cancer Hallmarks ◽  
Cerna Network ◽  
Comprehensive Database ◽  
User Friendly

Abstract LnCeVar (http://www.bio-bigdata.net/LnCeVar/) is a comprehensive database that aims to provide genomic variations that disturb lncRNA-associated competing endogenous RNA (ceRNA) network regulation curated from the published literature and high-throughput data sets. LnCeVar curated 119 501 variation–ceRNA events from thousands of samples and cell lines, including: (i) more than 2000 experimentally supported circulating, drug-resistant and prognosis-related lncRNA biomarkers; (ii) 11 418 somatic mutation–ceRNA events from TCGA and COSMIC; (iii) 112 674 CNV–ceRNA events from TCGA; (iv) 67 066 SNP–ceRNA events from the 1000 Genomes Project. LnCeVar provides a user-friendly searching and browsing interface. In addition, as an important supplement of the database, several flexible tools have been developed to aid retrieval and analysis of the data. The LnCeVar–BLAST interface is a convenient way for users to search ceRNAs by interesting sequences. LnCeVar–Function is a tool for performing functional enrichment analysis. LnCeVar–Hallmark identifies dysregulated cancer hallmarks of variation–ceRNA events. LnCeVar–Survival performs COX regression analyses and produces survival curves for variation–ceRNA events. LnCeVar–Network identifies and creates a visualization of dysregulated variation–ceRNA networks. Collectively, LnCeVar will serve as an important resource for investigating the functions and mechanisms of personalized genomic variations that disturb ceRNA network regulation in human diseases.

scholarly journals Genomic Variation in Micropropagated Robinia ambigua `idahoensis' Revealed by RAPD Markers

HortScience ◽  
2006 ◽  
Vol 41 (6) ◽  
pp. 1466-1468 ◽  
Author(s):  
Frederic Ngezahayo ◽  
Wanli Guo ◽  
Lei Gong ◽  
Fangxia Li ◽  
Bao Liu ◽  
...  
Keyword(s):  
Random Amplified Polymorphic Dna ◽  
Issr Markers ◽  
Genomic Variation ◽  
Axillary Buds ◽  
Donor Plant ◽  
Genomic Variations ◽  
Single Donor ◽  
Cellular Genes ◽  
Polymorphism Level

The authors have previously reported an efficient in vitro system for mass micropropagation of Robinia ambigua `idahoensis' (Idaho locust). Their method used enhanced branching of axillary buds from a single donor plant along with detection of somaclonal variation by the intersimple sequence repeat (ISSR) markers. Because ISSRs tend to be clustered to specific chromosomal regions in plant genomes, the extent and scope of the genomic variations and the sequences underlying the variation warranted further investigations. In this study, the authors analyzed the same set of 40 randomly selected micropropagated R. ambigua plants by a more general molecular marker—random amplified polymorphic DNA (RAPD) using 34 selected primers. In addition, they sequenced some of the variable bands. Of the 260 reproducible RAPD bands scored, 70 were polymorphic among the 41 plants (40 micropropagated and one donor), corresponding to a polymorphism level of 26%. Cluster analysis revealed a genetic similarity ranging from 0.61 to 0.97. Of the 20 sequenced bands underlying the variations, eight showed significant homology to known or predicted functional cellular genes or retroelements. These results clearly indicated that micropropagation of R. ambigua, even by enhanced branching of axillary buds, can be accompanied by extensive genomic variations, which should be taken into account for commercial propagation of this plant by in vitro means.

scholarly journals Transposons modulate transcriptomic and phenotypic variation via the formation of circular RNAs in maize

2017 ◽  
Author(s):  
Lu Chen ◽  
Pei Zhang ◽  
Yuan Fan ◽  
Juan Huang ◽  
Qiong Lu ◽  
...  
Keyword(s):  
Phenotypic Variation ◽  
Genomic Variation ◽  
Circular Rnas ◽  
Maize Genome ◽  
Proof Of Concept ◽  
High Confidence ◽  
Genomic Features ◽  
Rna Molecules ◽  
Expression Variation ◽  
Flanking Regions

AbstractCircular RNAs (circRNAs) are covalently closed, single-stranded RNA molecules. Recent studies in human showed that circRNAs can arise via transcription of reverse complementary pairs of transposons. Given the prevalence of transposons in the maize genome and dramatic genomic variation driven by transposons, we hypothesize that transposons in maize may be involved in the formation of circRNAs and further modulate phenotypic variation. To test our hypothesis, we performed circRNA-Seq on B73 seedling leaves and integrate these data with 977 publicly available mRNA-Seq datasets. We uncovered 1,551 high-confidence maize circRNAs, which show distinct genomic features as compared to linear transcripts. Comprehensive analyses demonstrated that LINE1-like elements (LLE) and their Reverse Complementary Pairs (LLERCPs) are significantly enriched in the flanking regions of circRNAs. Interestingly, the accumulation of circRNA transcripts increases, while the accumulation of linear transcripts decreases as the number of LLERCPs increases. Furthermore, genes with LLERCP-mediated circRNAs are enriched among loci that are associated with phenotypic variation. These results suggest that LLERCPs can modulate phenotypic variation by the formation of circRNAs. As a proof of concept, we showed that the presence/absence variation of LLERCPs could result in expression variation of one cicrRNA, circ352, and further related to plant height through the interaction between circRNA and functional linear transcript. Our first glimpse of circRNAs uncovers a new role for transposons in the modulation of transcriptomic and phenotypic variation via the formation of circRNAs.

scholarly journals Network Pharmacology-based Investigation of the Underlying Mechanism of Panax notoginseng Treatment of Diabetic Retinopathy

2020 ◽  
Vol 23 (4) ◽  
pp. 334-344
Author(s):  
Chunli Piao ◽  
Zheyu Sun ◽  
De Jin ◽  
Han Wang ◽  
Xuemin Wu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Mechanisms ◽  
Topological Analysis ◽  
Enrichment Analysis ◽  
Panax Notoginseng ◽  
Diabetic Microangiopathy ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Annotation Database ◽  
Cox 2

Background: Panax notoginseng, a Chinese herbal medicine, has been widely used to treat vascular diseases. Diabetic retinopathy (DR) is one of the complications of diabetic microangiopathy. According to recent studies, the application of Panax notoginseng extract and related Chinese patent medicine preparations can significantly improve DR. However, the pharmacological mechanisms remain unclear. Therefore, the purpose of this study was to decipher the potential mechanism of Panax notoginseng treatment of DR using network pharmacology. Methods: We evaluated and screened the active compounds of Panax notoginseng using the Traditional Chinese Medicine Systems Pharmacology database and collected potential targets of the compounds by target fishing. A multi-source database was also used to organize targets of DR. The potential targets as the treatment of DR with Panax notoginseng were then obtained by matching the compound targets with the DR targets. Using protein-protein interaction networks and topological analysis, interactions between potential targets were identified. In addition, we also performed gene ontology-biological process and pathway enrichment analysis for the potential targets by using the Biological Information Annotation Database. Results: Eight active ingredients of Panax notoginseng and 31 potential targets for the treatment of DR were identified. The screening and enrichment analysis revealed that the treatment of DR using Panax notoginseng primarily involved 28 biological processes and 10 related pathways. Further analyses indicated that angiogenesis, inflammatory reactions, and apoptosis may be the main processes involved in the treatment of DR with Panax notoginseng. In addition, we determined that the mechanism of intervention of Panax notoginseng in treating DR may involve five core targets, VEGFA, MMP-9, MMP-2, FGF2, and COX-2. Conclusion: Panax notoginseng may treat diabetic retinopathy through the mechanism of network pharmacological analysis. The underlying molecular mechanisms were closely related to the intervention of angiogenesis, inflammation, and apoptosis with VEGFA, MMP-9, MMP-2, FGF2, and COX-2 being possible targets.

scholarly journals SnpHub: an easy-to-set-up web server framework for exploring large-scale genomic variation data in the post-genomic era with applications in wheat

GigaScience ◽  
2020 ◽  
Vol 9 (6) ◽  
Author(s):  
Wenxi Wang ◽  
Zihao Wang ◽  
Xintong Li ◽  
Zhongfu Ni ◽  
Zhaorong Hu ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Genomic Variation ◽  
Published Data ◽  
Genomic Variations ◽  
Haplotype Networks ◽  
Variation Data ◽  
Set Up ◽  
Portal Website

Abstract Background The cost of high-throughput sequencing is rapidly decreasing, allowing researchers to investigate genomic variations across hundreds or even thousands of samples in the post-genomic era. The management and exploration of these large-scale genomic variation data require programming skills. The public genotype querying databases of many species are usually centralized and implemented independently, making them difficult to update with new data over time. Currently, there is a lack of a widely used framework for setting up user-friendly web servers to explore new genomic variation data in diverse species. Results Here, we present SnpHub, a Shiny/R-based server framework for retrieving, analysing, and visualizing large-scale genomic variation data that can be easily set up on any Linux server. After a pre-building process based on the provided VCF files and genome annotation files, the local server allows users to interactively access single-nucleotide polymorphisms and small insertions/deletions with annotation information by locus or gene and to define sample sets through a web page. Users can freely analyse and visualize genomic variations in heatmaps, phylogenetic trees, haplotype networks, or geographical maps. Sample-specific sequences can be accessed as replaced by detected sequence variations. Conclusions SnpHub can be applied to any species, and we build up a SnpHub portal website for wheat and its progenitors based on published data in recent studies. SnpHub and its tutorial are available at http://guoweilong.github.io/SnpHub/. The wheat-SnpHub-portal website can be accessed at http://wheat.cau.edu.cn/Wheat_SnpHub_Portal/.

scholarly journals The Role of SGLT2 Inhibitor on the Treatment of Diabetic Retinopathy

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Wenjun Sha ◽  
Song Wen ◽  
Lin Chen ◽  
Bilin Xu ◽  
Tao Lei ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Glucose Transporter ◽  
Early Stage ◽  
Sglt2 Inhibitor ◽  
Research Field ◽  
Research Progress ◽  
Diabetic Microangiopathy ◽  
Control Blood Glucose ◽  
Glucose Transporter 2 ◽  
Prevention And Treatment

Diabetic retinopathy (DR) is one of the most serious complications of diabetic microangiopathy. DR has an early onset and is not easy to detect. When visual impairment occurs, the optimal period for therapy is often missed. Therefore, the prevention and treatment of DR should start from the early stage of diabetes. Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) is a new antidiabetic drug which is mainly used in clinical practice to control blood glucose of patients with type 2 diabetes prone to develop chronic heart failure. Recent studies have found that SGLT2 is also expressed in the human retina. Now, the prevention and treatment of diabetic retinopathy with SGLT2i while reducing blood sugar has become a new research field. Hence, this article reviewed the recent therapeutic and research progress of SGLT2 in the treatment of diabetic retinopathy.

scholarly journals BnaGVD: A genomic variation database of rapeseed (Brassica napus)

2021 ◽  
Author(s):  
Tao Yan ◽  
Yao Yao ◽  
Dezhi Wu ◽  
Lixi Jiang
Keyword(s):  
Brassica Napus ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Sequence Data ◽  
Genomic Variation ◽  
High Quality ◽  
Brassica Napus L ◽  
Genomic Variations ◽  
Web Resource ◽  
Variation Database

Abstract Rapeseed (Brassica napus L.) is a typical polyploid crop and one of the most important oilseed crops worldwide. With the rapid progress on high-throughput sequencing technologies and the reduction of sequencing cost, large-scale genomic data of a specific crop have become available. However, raw sequence data are mostly deposited in the sequence read archive of the National Center of Biotechnology Information (NCBI) and the European Nucleotide Archive (ENA), which is freely accessible to all researchers. Extensive tools for practical purposes should be developed to efficiently utilize these large raw data. Here, we report a web-based rapeseed genomic variation database (BnaGVD, http://rapeseed.biocloud.net/home) from which genomic variations, such as single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) across a world-wide collection of rapeseed accessions, can be referred. The current release of the BnaGVD contains 34,591,899 high-quality SNPs and 12,281,923 high-quality InDels and provides search tools to retrieve genomic variations and gene annotations across 1,007 accessions of worldwide rapeseed germplasm. We implement a variety of built-in tools (e.g., BnaGWAS, BnaPCA, and BnaStructure) to help users perform in-depth analyses. We recommend this web resource for accelerating studies on the functional genomics and screening of molecular markers for rapeseed breeding.

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