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The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA) identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD) in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits) enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility from reanalysis of published GWA studies. We propose that dysregulation of monocyte adaptation to the environment of the gastrointestinal mucosa is the key process leading to inflammatory bowel disease.
Pubmed ID: 28263993 RIS Download
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BioLayout Express3D is a powerful new tool for the visualization and analysis of networks derived from biological systems. Network-based approaches are becoming increasing popular for the analysis of ''omics and other high dimensional data. Networks can be produced from a wide variety of biological relationships, such as interactions between individuals, disease transmission, sequence similarity, metabolic pathways, protein interactions, pathways, regulatory cascades, gene expression, etc. BioLayout Express3D has been specifically designed for visualization, clustering and analysis of large network graphs in two- and three-dimensional space derived primarily, but not exclusively, from biological data. Sponsors: This resource is supported by BBSRC (BB / F003722 / 1) and the Wellcome Trust (GR077040RP). Keywords: Biology, Tool, Software, visualization, Analysis, Network, Biological, System, Dimentional, Data, Disease, Transmission, Sequence, Metabolic, Pathway, Protein, Interaction, Gene, Expression, Clustering, Analysis,
View all literature mentionsCollection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.
View all literature mentionsExpression profiling and promoter identification software tool for transcriptional network analysis and transcriptome characterization. DeepCAGE, the combination of next-generation sequencing with next generation expression profiling provides unsurpassed solutions for expression profiling and genome annotation. CAGE will be the experimental approach at need to link gene expression and control regions in the genome. With the availability of next-generation sequencing methods, DNAFORM now offers DeepCAGE services. DeepCAGE libraries are prepared for direct analysis by an Illumina/Solexa Sequencer. One sequencing run using one channel on an Illumina/Solexa Sequencer can yield in over 4,000,000 reads per sample. CAGE is based on our full-length cDNA library technology, where an adaptor is ligated to the 5''''-end of full-length cDNAs, which introduces a recognition site for a Class IIs restriction endonuclease adjacent to the 5''''-end of the cDNA. The Class IIs restriction endonuclease, here MmeI, allows for the cloning of short tags as derived from the 5''''-end of transcripts into concatemers for high-throughput sequencing. CAGE tags are further characterized by mapping to genomic sequences, which enables the identification of transcriptional start sites. As such CAGE can contribute to projects in Gene Discovery, Gene Expression, and Promoter Identification. After the genome sequencing projects have provided us with the genetic blueprints for many organisms, new questions have to be answered on how to correlate the observed genotypes with related phenotypes, and how to understand the regulation of genetic information in time and space. The dynamics of living systems and the functional behavior of cells in multicellular organisms has thus become the subject of the emerging field of system biology. Integration of experimental approaches and computer aided theories on a system level will be the fundamental principle to drive systems biology in order to understand the principles behind complex regulatory networks, which will be an ambitious goal requiring new approaches in life sciences. For ordering and additional information, please contact us under contact_at_dnaform.jp
View all literature mentionsPython 2D plotting library which produces publication quality figures in variety of hardcopy formats and interactive environments across platforms. Used in python scripts, web application servers, and six graphical user interface toolkits. Used to generate plots, histograms, power spectra, bar charts, error charts, scatter plots.
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