scholarly journals Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jianghong Wu ◽  
Husile Gong ◽  
Yongsheng Bai ◽  
Wenguang Zhang
Keyword(s):  
Gene Networks ◽  
Regulatory Networks ◽  
Mirna Gene ◽  
Genetic Regulatory Networks ◽  
Host Immunity ◽  
Genetic Networks ◽  
Target Sites ◽  
Enormous Number ◽  
Human And Mouse

Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore,hsa-miR-548,mmu-miR-466, andmmu-miR-467have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse.

scholarly journals Detecting miRNA Mentions and Relations in Biomedical Literature

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 205 ◽  
Author(s):  
Shweta Bagewadi ◽  
Tamara Bobić ◽  
Martin Hofmann-Apitius ◽  
Juliane Fluck ◽  
Roman Klinger
Keyword(s):  
Regulatory Networks ◽  
Wide Spectrum ◽  
Mirna Gene ◽  
Biomedical Literature ◽  
Entity Recognition ◽  
Lower Sensitivity ◽  
Related Information ◽  
Manual Inspection ◽  
Number Of Publications

Introduction: MicroRNAs (miRNAs) have demonstrated their potential as post-transcriptional gene expression regulators, participating in a wide spectrum of regulatory events such as apoptosis, differentiation, and stress response. Apart from the role of miRNAs in normal physiology, their dysregulation is implicated in a vast array of diseases. Dissection of miRNA-related associations are valuable for contemplating their mechanism in diseases, leading to the discovery of novel miRNAs for disease prognosis, diagnosis, and therapy.Motivation: Apart from databases and prediction tools, miRNA-related information is largely available as unstructured text. Manual retrieval of these associations can be labor-intensive due to steadily growing number of publications. Additionally, most of the published miRNA entity recognition methods are keyword based, further subjected to manual inspection for retrieval of relations. Despite the fact that several databases host miRNA-associations derived from text, lower sensitivity and lack of published details for miRNA entity recognition and associated relations identification has motivated the need for developing comprehensive methods that are freely available for the scientific community. Additionally, the lack of a standard corpus for miRNA-relations has caused difficulty in evaluating the available systems.We propose methods to automatically extract mentions of miRNAs, species, genes/proteins, disease, and relations from scientific literature. Our generated corpora, along with dictionaries, and miRNA regular expression are freely available for academic purposes. To our knowledge, these resources are the most comprehensive developed so far.Results: The identification of specific miRNA mentions reaches a recall of 0.94 and precision of 0.93.  Extraction of miRNA-disease and miRNA-gene relations lead to an F1 score of up to 0.76. A comparison of the information extracted by our approach to the databases miR2Disease and miRSel for the extraction of Alzheimer's disease related relations shows the capability of our proposed methods in identifying correct relations with improved sensitivity. The published resources and described methods can help the researchers for maximal retrieval of miRNA-relations and generation of miRNA-regulatory networks.Availability: The training and test corpora, annotation guidelines, developed dictionaries, and supplementary files are available at http://www.scai.fraunhofer.de/mirna-corpora.html

scholarly journals The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers

2021 ◽  
Vol 22 (16) ◽  
pp. 8527
Author(s):  
Leila Jahangiri ◽  
Perla Pucci ◽  
Tala Ishola ◽  
Ricky M. Trigg ◽  
John A. Williams ◽  
...  
Keyword(s):  
Gene Networks ◽  
Regulatory Networks ◽  
Metabolic Reprogramming ◽  
Cellular Processes ◽  
Cancer Genomes ◽  
Mutual Regulation ◽  
Myc Gene ◽  
Gene Regulatory ◽  
Non Coding Rnas

MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.

scholarly journals Conservation and novelty in the microRNA genomic landscape of hyperdiverse cichlid fishes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Peiwen Xiong ◽  
Ralf F. Schneider ◽  
C. Darrin Hulsey ◽  
Axel Meyer ◽  
Paolo Franchini
Keyword(s):  
Messenger Rna ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Protein Coding ◽  
Adaptive Diversification ◽  
Cichlid Fishes ◽  
Novel Mirna ◽  
Genomic Landscape ◽  
Target Sites

Abstract MicroRNAs (miRNAs) play crucial roles in the post-transcriptional control of messenger RNA (mRNA). These miRNA-mRNA regulatory networks are present in nearly all organisms and contribute to development, phenotypic divergence, and speciation. To examine the miRNA landscape of cichlid fishes, one of the most species-rich families of vertebrates, we profiled the expression of both miRNA and mRNA in a diverse set of cichlid lineages. Among these, we found that conserved miRNAs differ from recently arisen miRNAs (i.e. lineage specific) in average expression levels, number of target sites, sequence variability, and physical clustering patterns in the genome. Furthermore, conserved miRNA target sites tend to be enriched at the 5′ end of protein-coding gene 3′ UTRs. Consistent with the presumed regulatory role of miRNAs, we detected more negative correlations between the expression of miRNA-mRNA functional pairs than in random pairings. Finally, we provide evidence that novel miRNA targets sites are enriched in genes involved in protein synthesis pathways. Our results show how conserved and evolutionarily novel miRNAs differ in their contribution to the genomic landscape and highlight their particular evolutionary roles in the adaptive diversification of cichlids.

scholarly journals Detecting miRNA Mentions and Relations in Biomedical Literature

F1000Research ◽  
2015 ◽  
Vol 3 ◽  
pp. 205 ◽  
Author(s):  
Shweta Bagewadi ◽  
Tamara Bobić ◽  
Martin Hofmann-Apitius ◽  
Juliane Fluck ◽  
Roman Klinger
Keyword(s):  
Regulatory Networks ◽  
Wide Spectrum ◽  
Mirna Gene ◽  
Biomedical Literature ◽  
Entity Recognition ◽  
Lower Sensitivity ◽  
Related Information ◽  
Manual Inspection ◽  
Number Of Publications

Introduction: MicroRNAs (miRNAs) have demonstrated their potential as post-transcriptional gene expression regulators, participating in a wide spectrum of regulatory events such as apoptosis, differentiation, and stress response. Apart from the role of miRNAs in normal physiology, their dysregulation is implicated in a vast array of diseases. Dissection of miRNA-related associations are valuable for contemplating their mechanism in diseases, leading to the discovery of novel miRNAs for disease prognosis, diagnosis, and therapy.Motivation: Apart from databases and prediction tools, miRNA-related information is largely available as unstructured text. Manual retrieval of these associations can be labor-intensive due to steadily growing number of publications. Additionally, most of the published miRNA entity recognition methods are keyword based, further subjected to manual inspection for retrieval of relations. Despite the fact that several databases host miRNA-associations derived from text, lower sensitivity and lack of published details for miRNA entity recognition and associated relations identification has motivated the need for developing comprehensive methods that are freely available for the scientific community. Additionally, the lack of a standard corpus for miRNA-relations has caused difficulty in evaluating the available systems.We propose methods to automatically extract mentions of miRNAs, species, genes/proteins, disease, and relations from scientific literature. Our generated corpora, along with dictionaries, and miRNA regular expression are freely available for academic purposes. To our knowledge, these resources are the most comprehensive developed so far.Results: The identification of specific miRNA mentions reaches a recall of 0.94 and precision of 0.93.  Extraction of miRNA-disease and miRNA-gene relations lead to an F1 score of up to 0.76. A comparison of the information extracted by our approach to the databases miR2Disease and miRSel for the extraction of Alzheimer's disease related relations shows the capability of our proposed methods in identifying correct relations with improved sensitivity. The published resources and described methods can help the researchers for maximal retrieval of miRNA-relations and generation of miRNA-regulatory networks.Availability: The training and test corpora, annotation guidelines, developed dictionaries, and supplementary files are available at http://www.scai.fraunhofer.de/mirna-corpora.html

Abstract 386: Identification of Genetic Regulatory Networks for Insulin Resistance in Multiple Populations of Diverse Ethnicities

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Le Shu ◽  
Yuqi Zhao ◽  
Aldons J Lusis ◽  
Ke Hao ◽  
Thomas Quertermous ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Graphical Models ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Association Studies ◽  
Network Models ◽  
Mapk Signaling ◽  
Genetic Regulatory Networks ◽  
Specific Gene ◽  
Genome Wide Association Studies

Insulin resistance (IR) is a critical pathogenic factor for highly prevalent modern cardiometabolic diseases, including coronary artery disease (CAD) and type 2 diabetes (T2D). However, the molecular circuitries underlying IR remain to be elucidated. The GENEticS of Insulin Sensitivity Consortium (GENESIS) conducted genome-wide association studies (GWAS) for direct measures of IR using euglycemic clamp or insulin suppression test. We sought to identify gene networks and their key intervening drivers for IR by performing a comprehensive integrative analysis leveraging GWAS data from seven GENESIS cohorts representing three ethnic groups - Europeans, Asians and Hispanics, along with expression quantitative trait loci, ENCODE, and tissue-specific gene network models (both co-expression and graphical models) from IR relevant tissues. Integration of the multi-ethnic GWAS with diverse functional genomics information captured shared IR pathways and networks across ethnicities that are independent of body mass index, including GLUT4 translocation regulation, insulin signaling, MAPK signaling, interleukin signaling, extracellular matrix, branched-chain amino acids metabolisms, cell cycle, and oxidative phosphorylation. Further integration of these GWAS-informed IR processes with graphical gene networks uncovered potential key regulators including HADH, COX5A, VCAN and TOP2A , whose network neighbors are consistently enriched for the genetic association signals of IR across ethnicities, and show significant correlation with IR, fasting glucose and insulin levels in the transcriptomic-wide association data from a Hybrid Mouse Diversity Panel comprised of >100 strains fed with high-fat diet. Findings from this in-depth assessment of genetic and functional data from multiple human cohorts provide new understanding of the pathways, gene networks and potential regulators contributing to IR. These results will also facilitate future functional investigations to unveil how DNA variations translate into IR.

scholarly journals Complex and unexpected dynamics in simple genetic regulatory networks

2014 ◽  
Vol 28 (14) ◽  
pp. 1430006 ◽  
Author(s):  
Yanika Borg ◽  
Ekkehard Ullner ◽  
Afnan Alagha ◽  
Ahmed Alsaedi ◽  
Darren Nesbeth ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Complex Dynamics ◽  
Dynamical Behavior ◽  
Genetic Regulatory Networks ◽  
Genetic Networks ◽  
Emergent Properties ◽  
Coupling Mechanism ◽  
Bistable Systems ◽  
Large Populations ◽  
External Signals

One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.

scholarly journals GeneVis: Simulation and Visualization of Genetic Networks

2003 ◽  
Vol 2 (4) ◽  
pp. 201-217 ◽  
Author(s):  
Charles Baker ◽  
Sheelagh Carpendale ◽  
Przemyslaw Prusinkiewicz ◽  
Michael Surette
Keyword(s):  
Network Structure ◽  
Base Pair ◽  
Regulatory Networks ◽  
Protein Concentration ◽  
Genetic Network ◽  
Genetic Regulatory Networks ◽  
Genetic Networks ◽  
Structure Representation ◽  
Individual Protein ◽  
The Individual

GeneVis simulates genetic networks and visualizes the process of this simulation interactively, providing a visual environment for exploring the dynamics of genetic regulatory networks. The visualization environment supports several representational modes, which include: an individual protein representation, a protein concentration representation, and a network structure representation. The individual protein representation shows the activities of the individual proteins. The protein concentration representation illustrates the relative spread and concentrations of the different proteins in the simulation. The network structure representation depicts the genetic network dependencies that are present in the simulation. GeneVis includes several interactive viewing tools. These include animated transitions from the individual protein representation to the protein concentration representation and from the individual protein representation to the network structure representation. Three types of lenses are used to provide different views within a representation: fuzzy lenses, base pair lenses, and the network structure ring lens. With a fuzzy lens an alternate representation can be viewed in a selected region. The base pair lenses allow users to reposition genes for better viewing or to minimize interference during the simulation. The ring lens provides detail-in-context viewing of individual levels in the genetic network structure representation.

scholarly journals Reproductive barriers as a byproduct of gene network evolution

2020 ◽  
Author(s):  
Chia-Hung Yang ◽  
Samuel V. Scarpino
Keyword(s):  
Natural Selection ◽  
Reproductive Isolation ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Network Evolution ◽  
Genetic Interactions ◽  
Reproductive Barriers ◽  
Evolutionary Forces ◽  
Functional Representation

AbstractMolecular analyses of closely related taxa have increasingly revealed the importance of higher-order genetic interactions in explaining the observed pattern of reproductive isolation between populations. Indeed, both empirical and theoretical studies have linked the process of speciation to complex genetic interactions. Gene Regulatory Networks (GRNs) capture the inter-dependencies of gene expression and encode information about an individual’s phenotype and development at the molecular level. As a result, GRNs can–in principle–evolve via natural selection and play a role in non-selective, evolutionary forces. Here, we develop a network-based model, termed the pathway framework, that considers GRNs as a functional representation of coding sequences. We then simulated the dynamics of GRNs using a simple model that included natural selection, genetic drift, and sexual reproduction and found that reproductive barriers can develop rapidly between allopatric populations experiencing identical selection pressure. Further, we show that alleles involved in reproductive isolation can predate the allopatric separation of populations and that the number of interacting loci involved in genetic incompatibilities, i.e., the order, is often high simply as a by-product of the networked structure of GRNs. Finally, we discuss how results from the pathway framework are consistent with observed empirical patterns for genes putatively involved in post-zygotic isolation. Taken together, this study adds support for the central role of gene networks in speciation and in evolution more broadly.

scholarly journals CircRNAs Dysregulated in Juvenile Myelomonocytic Leukemia: CircMCTP1 Stands Out

2021 ◽  
Vol 8 ◽  
Author(s):  
Anna Dal Molin ◽  
Mattias Hofmans ◽  
Enrico Gaffo ◽  
Alessia Buratin ◽  
Hélène Cavé ◽  
...  
Keyword(s):  
Gene Networks ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Mirna Gene ◽  
Myeloproliferative Neoplasm ◽  
Independent Set ◽  
Circular Rnas ◽  
Juvenile Myelomonocytic Leukemia ◽  
Ras Signaling ◽  
Myelomonocytic Leukemia

Juvenile myelomonocytic leukemia (JMML), a rare myelodysplastic/myeloproliferative neoplasm of early childhood, is characterized by clonal growth of RAS signaling addicted stem cells. JMML subtypes are defined by specific RAS pathway mutations and display distinct gene, microRNA (miRNA) and long non-coding RNA expression profiles. Here we zoom in on circular RNAs (circRNAs), molecules that, when abnormally expressed, may participate in malignant deviation of cellular processes. CirComPara software was used to annotate and quantify circRNAs in RNA-seq data of a “discovery cohort” comprising 19 JMML patients and 3 healthy donors (HD). In an independent set of 12 JMML patients and 6 HD, expression of 27 circRNAs was analyzed by qRT-PCR. CircRNA-miRNA-gene networks were reconstructed using circRNA function prediction and gene expression data. We identified 119 circRNAs dysregulated in JMML and 59 genes showing an imbalance of the circular and linear products. Our data indicated also circRNA expression differences among molecular subgroups of JMML. Validation of a set of deregulated circRNAs in an independent cohort of JMML patients confirmed the down-regulation of circOXNAD1 and circATM, and a marked up-regulation of circLYN, circAFF2, and circMCTP1. A new finding in JMML links up-regulated circMCTP1 with known tumor suppressor miRNAs. This and other predicted interactions with miRNAs connect dysregulated circRNAs to regulatory networks. In conclusion, this study provides insight into the circRNAome of JMML and paves the path to elucidate new molecular disease mechanisms putting forward circMCTP1 up-regulation as a robust example.

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