Dataset Information

Tissue-specific expression and regulatory networks of pig microRNAome.

ABSTRACT: BACKGROUND: Despite the economic and medical importance of the pig, knowledge about its genome organization, gene expression regulation, and molecular mechanisms involved in physiological processes is far from that achieved for mouse and rat, the two most used model organisms in biomedical research. MicroRNAs (miRNAs) are a wide class of molecules that exert a recognized role in gene expression modulation, but only 280 miRNAs in pig have been characterized to date. RESULTS: We applied a novel computational approach to predict species-specific and conserved miRNAs in the pig genome, which were then subjected to experimental validation. We experimentally identified candidate miRNAs sequences grouped in high-confidence (424) and medium-confidence (353) miRNAs according to RNA-seq results. A group of miRNAs was also validated by PCR experiments. We established the subtle variability in expression of isomiRs and miRNA-miRNA star couples supporting a biological function for these molecules. Finally, miRNA and mRNA expression profiles produced from the same sample of 20 different tissue of the animal were combined, using a correlation threshold to filter miRNA-target predictions, to identify tissue-specific regulatory networks. CONCLUSIONS: Our data represent a significant progress in the current understanding of miRNAome in pig. The identification of miRNAs, their target mRNAs, and the construction of regulatory circuits will provide new insights into the complex biological networks in several tissues of this important animal model.

SUBMITTER: Martini P

PROVIDER: S-EPMC3974652 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Tissue-specific expression and regulatory networks of pig microRNAome.

Martini Paolo P Sales Gabriele G Brugiolo Mattia M Gandaglia Alessandro A Naso Filippo F De Pittà Cristiano C Spina Michele M Gerosa Gino G Chemello Francesco F Romualdi Chiara C Cagnin Stefano S Lanfranchi Gerolamo G

PloS one 20140403 4

<h4>Background</h4>Despite the economic and medical importance of the pig, knowledge about its genome organization, gene expression regulation, and molecular mechanisms involved in physiological processes is far from that achieved for mouse and rat, the two most used model organisms in biomedical research. MicroRNAs (miRNAs) are a wide class of molecules that exert a recognized role in gene expression modulation, but only 280 miRNAs in pig have been characterized to date.<h4>Results</h4>We appli ...[more]

PMID: 24699212

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Project description:BackgroundTranscription factors (TFs) and miRNAs are essential for the regulation of gene expression; however, the global view of human gene regulatory networks remains poorly understood. For example, how is the expression of so many genes regulated by limited cohorts of regulators and how are genes differentially expressed in different tissues despite the genetic code being the same in all tissues?ResultsWe analyzed the network properties of housekeeping and tissue-specific genes in gene regulatory networks from seven human tissues. Our results show that different classes of genes behave quite differently in these networks. Tissue-specific miRNAs show a higher average target number compared with non-tissue specific miRNAs, which indicates that tissue-specific miRNAs tend to regulate different sets of targets. Tissue-specific TFs exhibit higher in-degree, out-degree, cluster coefficient and betweenness values, indicating that they occupy central positions in the regulatory network and that they transfer genetic information from upstream genes to downstream genes more quickly than other TFs. Housekeeping TFs tend to have higher cluster coefficients compared with other genes that are neither housekeeping nor tissue specific, indicating that housekeeping TFs tend to regulate their targets synergistically. Several topological properties of disease-associated miRNAs and genes were found to be significantly different from those of non-disease-associated miRNAs and genes.ConclusionsTissue-specific miRNAs, TFs and disease genes have particular topological properties within the transcriptional regulatory networks of the seven human tissues examined. The tendency of tissue-specific miRNAs to regulate different sets of genes shows that a particular tissue-specific miRNA and its target gene set may form a regulatory module to execute particular functions in the process of tissue differentiation. The regulatory patterns of tissue-specific TFs reflect their vital role in regulatory networks and their importance to biological functions in their respective tissues. The topological differences between disease and non-disease genes may aid the discovery of new disease genes or drug targets. Determining the network properties of these regulatory factors will help define the basic principles of human gene regulation and the molecular mechanisms of disease.

Project description:BACKGROUND:Recent advances in sequencing technologies have enabled parallel assays of chromatin accessibility and gene expression for major human cell lines. Such innovation provides a great opportunity to decode phenotypic consequences of genetic variation via the construction of predictive gene regulatory network models. However, there still lacks a computational method to systematically integrate chromatin accessibility information with gene expression data to recover complicated regulatory relationships between genes in a tissue-specific manner. RESULTS:We propose a Markov random field (MRF) model for constructing tissue-specific transcriptional regulatory networks via integrative analysis of DNase-seq and RNA-seq data. Our method, named CSNets (cell-line specific regulatory networks), first infers regulatory networks for individual cell lines using chromatin accessibility information, and then fine-tunes these networks using the MRF based on pairwise similarity between cell lines derived from gene expression data. Using this method, we constructed regulatory networks specific to 110 human cell lines and 13 major tissues with the use of ENCODE data. We demonstrated the high quality of these networks via comprehensive statistical analysis based on ChIP-seq profiles, functional annotations, taxonomic analysis, and literature surveys. We further applied these networks to analyze GWAS data of Crohn's disease and prostate cancer. Results were either consistent with the literature or provided biological insights into regulatory mechanisms of these two complex diseases. The website of CSNets is freely available at http://bioinfo.au.tsinghua.edu.cn/jianglab/CSNETS/ . CONCLUSIONS:CSNets demonstrated the power of joint analysis on epigenomic and transcriptomic data towards the accurate construction of gene regulatory network. Our work provides not only a useful resource of regulatory networks to the community, but also valuable experiences in methodology development for multi-omics data integration.

Project description:BackgroundTranscription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM and seed) in maize. We utilized GENIE3, a machine-learning algorithm combined with large quantity of RNA-Seq expression data to construct four tissue-specific GRNs. Unlike some other techniques, this approach is not limited by high-quality Position Weighed Matrix (PWM), and can therefore predict GRNs for over 2000 TFs in maize.ResultsAlthough many TFs were expressed across multiple tissues, a multi-tiered analysis predicted tissue-specific regulatory functions for many transcription factors. Some well-studied TFs emerged within the four tissue-specific GRNs, and the GRN predictions matched expectations based upon published results for many of these examples. Our GRNs were also validated by ChIP-Seq datasets (KN1, FEA4 and O2). Key TFs were identified for each tissue and matched expectations for key regulators in each tissue, including GO enrichment and identity with known regulatory factors for that tissue. We also found functional modules in each network by clustering analysis with the MCL algorithm.ConclusionsBy combining publicly available genome-wide expression data and network analysis, we can uncover GRNs at tissue-level resolution in maize. Since ChIP-Seq and PWMs are still limited in several model organisms, our study provides a uniform platform that can be adapted to any species with genome-wide expression data to construct GRNs. We also present a publicly available database, maize tissue-specific GRN (mGRN, https://www.bio.fsu.edu/mcginnislab/mgrn/ ), for easy querying. All source code and data are available at Github ( https://github.com/timedreamer/maize_tissue-specific_GRN ).

Dataset Information

Tissue-specific expression and regulatory networks of pig microRNAome.

Publications

Tissue-specific expression and regulatory networks of pig microRNAome.

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