scholarly journals Contribution of Network Connectivity in Determining the Relationship between Gene Expression and Metabolite Concentration Changes

2014 ◽  
Vol 10 (4) ◽  
pp. e1003572 ◽  
Author(s):  
Aleksej Zelezniak ◽  
Steven Sheridan ◽  
Kiran Raosaheb Patil
Keyword(s):  
Gene Expression ◽  
Network Connectivity ◽  
Metabolite Concentration ◽  
Concentration Changes ◽  
The Relationship

scholarly journals Gene co-expression network connectivity is an important determinant of selective constraint

2016 ◽  
Author(s):  
Niklas Mähler ◽  
Jing Wang ◽  
Barbara K Terebieniec ◽  
Pär K Ingvarsson ◽  
Nathaniel R Street ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Genetic Architecture ◽  
Natural Variation ◽  
Network Connectivity ◽  
Purifying Selection ◽  
Selective Constraint ◽  
Effect Sizes ◽  
Signatures Of Selection ◽  
The Relationship

AbstractWhile several studies have investigated general properties of the genetic architecture of natural variation in gene expression, few of these have considered natural, outbreeding populations. In parallel, systems biology has established that a general feature of biological networks is that they are scale-free, rendering them buffered against random mutations. To date, few studies have attempted examine the relationship between the selective processes acting to maintain natural variation of gene expression and the associated co-expression network structure. Here we utilised RNA-Sequencing to assay gene expression in winter buds undergoing bud flush in a natural population of Populus tremula, and outbreeding forest tree species. We performed expression Quantitative Trait Locus (eQTL) mapping and identified 164,290 significant eQTLs associating 6,241 unique genes (eGenes) with 147,419 unique SNPs (eSNPs). We found approximately four times as many local as distant eQTLs, with local eQTLs having significantly higher effect sizes. eQTLs were primarily located in regulatory regions of genes (UTRs or flanking regions), regardless of whether they were local or distant. We used the gene expression data to infer a co-expression network and investigated the relationship between network topology, the genetic architecture of gene expression and signatures of selection. Within the co-expression network, eGenes were underrepresented in network module cores (hubs) and overrepresented in the periphery of the network, with a negative correlation between eQTL effect size and network connectivity. We additionally found that module core genes have experienced stronger selective constraint on coding and non-coding sequence, with connectivity associated with signatures of selection. Our integrated genetics and genomics results suggest that purifying selection is the primary mechanism underlying the genetic architecture of natural variation in gene expression assayed in flushing leaf buds of P. tremula and that connectivity within the co-expression network is linked to the strength of purifying selection.Author summaryNumerous studies have shown that many genomic polymorphisms contributing to phenotypic variation are located outside of protein coding regions, suggesting that they act by modulating gene expression. Furthermore, phenotypes are seldom explained by individual genes, but rather emerge from networks of interacting genes. The effect of regulatory variants and the interaction of genes can be described by co-expression networks, which are known to contain a small number of highly connected nodes and many more lowly connected nodes, making them robust to random mutation. While previous studies have examined the genetic architecture of gene expression variation, few were performed in natural populations with fewer still integrating the co-expression network.We undertook a study using a natural population of European aspen (Populus tremula), showing that highly connected genes within the co-expression network had lower levels of polymorphism, had polymorphisms segregating at lower frequencies and with lower than average effect sizes, suggesting purifying selection acts on central components of the network. Furthermore, the most highly connected genes within co-expression network hubs were underrepresented for identified expression quantitative trait loci, suggesting that purifying selection on individual SNPs is driven by stabilising selecting on gene expression. In contrast, genes in the periphery of the network displayed signatures of relaxed selective constraint. Highly connected genes are therefore buffered against large expression modulation, providing a mechanistic link between selective pressures and network toplogy, which act in cohort to maintain the robustness at the population level of the co-expression network derived from flushing buds in P. tremula.

Contribution a la rationalisation du reseau qualite de l’eau de la Baie James

1977 ◽  
Vol 12 (1) ◽  
pp. 51-76
Author(s):  
B. Bobée ◽  
D. Cluis ◽  
A. Tessier
Keyword(s):  
Correspondence Analysis ◽  
Major Ions ◽  
Base Station ◽  
Base Stations ◽  
James Bay ◽  
Mean Values ◽  
Multivariate Technique ◽  
Qualité De L’Eau ◽  
Concentration Changes ◽  
The Relationship

Abstract A water quality sampling programme for James Bay territory established in a previous study has been carried out for the Department of Natural Resources of the Province of Quebec. The network is composed of 5 base-stations, sampled every fortnight to determine the variability with time of the parameters and 16 satellite-stations, sampled five times yearly with a view to determine the spatial variability. The data (major ions and certain nutrients) gathered during the 1974–1975 field survey are subjected to an analysis by a multivariate technique (correspondence analysis) in addition to certain classical statistical methods. The latter have shown that the mean values obtained at satellite stations were representative of the annual mean. In addition, the results permit the determination for a given parameter, of the relationship between stations and, for a given station, the relationship between parameters. In both cases, the formulation of predictive equations was attempted. An overall evaluation of the data by correspondence analysis has permitted: - a more precise definition of the qualitative behaviour of the different sub-basins of the James Bay territory and characterization of their waters;- a proof of the existence of gradual concentration changes in both East-West and North-South directions. Within the original objectives of the network, the results of the study have led to the following recommendations: - to continue synchronised samplings;- to transform a base station with a low information content into a satellite station;- to create a new base station in the eastern part of the territory.

scholarly journals Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1021
Author(s):  
Carla Abrahamian ◽  
Christian Grimm
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Convincing Evidence ◽  
Signaling Cascades ◽  
Cation Channels ◽  
Pore Channel ◽  
Different Types ◽  
Canonical Wnt ◽  
The Relationship

Microphthalmia-associated transcription factor (MITF) is the principal transcription factor regulating pivotal processes in melanoma cell development, growth, survival, proliferation, differentiation and invasion. In recent years, convincing evidence has been provided attesting key roles of endolysosomal cation channels, specifically TPCs and TRPMLs, in cancer, including breast cancer, glioblastoma, bladder cancer, hepatocellular carcinoma and melanoma. In this review, we provide a gene expression profile of these channels in different types of cancers and decipher their roles, in particular the roles of two-pore channel 2 (TPC2) and TRPML1 in melanocytes and melanoma. We specifically discuss the signaling cascades regulating MITF and the relationship between endolysosomal cation channels, MAPK, canonical Wnt/GSK3 pathways and MITF.

scholarly journals Study on the Relationship between the miRNA-centered ceRNA Regulatory Network and Fatigue

2021 ◽  
Author(s):  
Xingzhe Yang ◽  
Feng Li ◽  
Jie Ma ◽  
Yan Liu ◽  
Xuejiao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Hot Spot ◽  
Genetic Research ◽  
Noncoding Rnas ◽  
Messenger Rnas ◽  
Effective Prevention ◽  
Gene Regulatory ◽  
The Relationship

AbstractIn recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.

scholarly journals Glutamate connectivity associations converge upon the salience network in schizophrenia and healthy controls

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert A. McCutcheon ◽  
Toby Pillinger ◽  
Maria Rogdaki ◽  
Juan Bustillo ◽  
Oliver D. Howes
Keyword(s):  
Functional Connectivity ◽  
Frontal Cortex ◽  
Network Connectivity ◽  
Resonance Spectroscopy ◽  
Salience Network ◽  
Healthy Controls ◽  
1H Mrs ◽  
Before And After ◽  
Functional Brain Networks ◽  
The Relationship

AbstractAlterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p < 0.05) and did not differ significantly between patients and controls (p > 0.85). Study B involved 19 individuals with schizophrenia and 17 controls and found that increases in glutamate concentrations induced by riluzole were linked to increases in connectivity localised to the salience network (p < 0.05), and the relationship did not differ between patients and controls (p > 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.

scholarly journals The Relationship among Gene Expression, the Evolution of Gene Dosage, and the Rate of Protein Evolution

PLoS Genetics ◽  
2010 ◽  
Vol 6 (5) ◽  
pp. e1000944 ◽  
Author(s):  
Jean-François Gout ◽  
Daniel Kahn ◽  
Laurent Duret ◽  
Keyword(s):  
Gene Expression ◽  
Protein Evolution ◽  
Gene Dosage ◽  
The Relationship
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