Dataset Information

Gene's hubs in retinal diseases: A retinal disease network.

ABSTRACT: Background:Retinal diseases associated with the dysfunction or death of photoreceptors are a major cause of blindness around the world, improvements in genetics tools, like next generation sequencing (NGS) allows the discovery of genes and genetic changes that lead to many of those retinal diseases. Though, there very few databases that explores a wide spectrum of retinal diseases, phenotypes, genes, and proteins, thus creating the need for a more comprehensive database, that groups all these parameters. Methods:Multiple open access databases were compiled into a new comprehensive database. A biological network was then crated, and organized using Cytoscape. The network was scrutinized for presence of hubs, measuring the concentration of grouped nodes. Finally, a trace back analysis was performed in areas were the power law reports a high r-squared value near one, that indicates high nodes density. Results:This work leads to creation of a retinal database that includes 324 diseases, 803 genes, 463 phenotypes, and 2461 proteins. Four biological networks (1) a disease and gene network connected by common phenotypes, (2) a disease and phenotype network connected by common genes, (3) a disease and gene network with shared disease or gene as the cause of an edge, and (4) a protein and disease network. The resulting networks will allow users to have easier searching for retinal diseases, phenotypes, genes, and proteins and their interrelationships. Conclusions:These networks have a broader range of information than previously available ones, helping clinicians in the comprehension of this complex group of diseases.

SUBMITTER: Lazaro-Guevara JM

PROVIDER: S-EPMC6218668 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Gene's hubs in retinal diseases: A retinal disease network.

Lázaro-Guevara J M JM Flores-Robles B J BJ Garrido K K Pinillos-Aransay V V Elena-Ibáñez A A Merino-Meléndez L L López-Martínez J A JA Victoriano-Lacalle R R

Heliyon 20181001 10

<h4>Background</h4>Retinal diseases associated with the dysfunction or death of photoreceptors are a major cause of blindness around the world, improvements in genetics tools, like next generation sequencing (NGS) allows the discovery of genes and genetic changes that lead to many of those retinal diseases. Though, there very few databases that explores a wide spectrum of retinal diseases, phenotypes, genes, and proteins, thus creating the need for a more comprehensive database, that groups all ...[more]

PMID: 30417144

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Project description:BACKGROUND:Although a number of recent studies have uncovered remarkable diversity of microbes associated with plants, understanding and managing dynamics of plant microbiomes remain major scientific challenges. In this respect, network analytical methods have provided a basis for exploring "hub" microbial species, which potentially organize community-scale processes of plant-microbe interactions. METHODS:By compiling Illumina sequencing data of root-associated fungi in eight forest ecosystems across the Japanese Archipelago, we explored hubs within "metacommunity-scale" networks of plant-fungus associations. In total, the metadata included 8080 fungal operational taxonomic units (OTUs) detected from 227 local populations of 150 plant species/taxa. RESULTS:Few fungal OTUs were common across all the eight forests. However, in each of the metacommunity-scale networks representing northern four localities or southern four localities, diverse mycorrhizal, endophytic, and pathogenic fungi were classified as "metacommunity hubs," which were detected from diverse host plant taxa throughout a climatic region. Specifically, Mortierella (Mortierellales), Cladophialophora (Chaetothyriales), Ilyonectria (Hypocreales), Pezicula (Helotiales), and Cadophora (incertae sedis) had broad geographic and host ranges across the northern (cool-temperate) region, while Saitozyma/Cryptococcus (Tremellales/Trichosporonales) and Mortierella as well as some arbuscular mycorrhizal fungi were placed at the central positions of the metacommunity-scale network representing warm-temperate and subtropical forests in southern Japan. CONCLUSIONS:The network theoretical framework presented in this study will help us explore prospective fungi and bacteria, which have high potentials for agricultural application to diverse plant species within each climatic region. As some of those fungal taxa with broad geographic and host ranges have been known to promote the survival and growth of host plants, further studies elucidating their functional roles are awaited.

Project description:Regulatory and developmental systems produce phenotypes that are robust to environmental and genetic variation. A gene product that normally contributes to this robustness is termed a phenotypic capacitor. When a phenotypic capacitor fails, for example when challenged by a harsh environment or mutation, the system becomes less robust and thus produces greater phenotypic variation. A functional phenotypic capacitor provides a mechanism by which hidden polymorphism can accumulate, whereas its failure provides a mechanism by which evolutionary change might be promoted. The primary example to date of a phenotypic capacitor is Hsp90, a molecular chaperone that targets a large set of signal transduction proteins. In both Drosophila and Arabidopsis, compromised Hsp90 function results in pleiotropic phenotypic effects dependent on the underlying genotype. For some traits, Hsp90 also appears to buffer stochastic variation, yet the relationship between environmental and genetic buffering remains an important unresolved question. We previously used simulations of knockout mutations in transcriptional networks to predict that many gene products would act as phenotypic capacitors. To test this prediction, we use high-throughput morphological phenotyping of individual yeast cells from single-gene deletion strains to identify gene products that buffer environmental variation in Saccharomyces cerevisiae. We find more than 300 gene products that, when absent, increase morphological variation. Overrepresented among these capacitors are gene products that control chromosome organization and DNA integrity, RNA elongation, protein modification, cell cycle, and response to stimuli such as stress. Capacitors have a high number of synthetic-lethal interactions but knockouts of these genes do not tend to cause severe decreases in growth rate. Each capacitor can be classified based on whether or not it is encoded by a gene with a paralog in the genome. Capacitors with a duplicate are highly connected in the protein-protein interaction network and show considerable divergence in expression from their paralogs. In contrast, capacitors encoded by singleton genes are part of highly interconnected protein clusters whose other members also tend to affect phenotypic variability or fitness. These results suggest that buffering and release of variation is a widespread phenomenon that is caused by incomplete functional redundancy at multiple levels in the genetic architecture.

Dataset Information

Gene's hubs in retinal diseases: A retinal disease network.

Publications

Gene's hubs in retinal diseases: A retinal disease network.

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