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      Tissue enrichment analysis for C. elegans genomics

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          Abstract

          Background

          Over the last ten years, there has been explosive development in methods for measuring gene expression. These methods can identify thousands of genes altered between conditions, but understanding these datasets and forming hypotheses based on them remains challenging. One way to analyze these datasets is to associate ontologies (hierarchical, descriptive vocabularies with controlled relations between terms) with genes and to look for enrichment of specific terms. Although Gene Ontology (GO) is available for Caenorhabditis elegans, it does not include anatomical information.

          Results

          We have developed a tool for identifying enrichment of C. elegans tissues among gene sets and generated a website GUI where users can access this tool. Since a common drawback to ontology enrichment analyses is its verbosity, we developed a very simple filtering algorithm to reduce the ontology size by an order of magnitude. We adjusted these filters and validated our tool using a set of 30 gold standards from Expression Cluster data in WormBase. We show our tool can even discriminate between embryonic and larval tissues and can even identify tissues down to the single-cell level. We used our tool to identify multiple neuronal tissues that are down-regulated due to pathogen infection in C. elegans.

          Conclusions

          Our Tissue Enrichment Analysis (TEA) can be found within WormBase, and can be downloaded using Python’s standard pip installer. It tests a slimmed-down C. elegans tissue ontology for enrichment of specific terms and provides users with a text and graphic representation of the results.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12859-016-1229-9) contains supplementary material, which is available to authorized users.

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          Most cited references21

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Gene Ontology: tool for the unification of biology

            Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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              FunRich: An open access standalone functional enrichment and interaction network analysis tool.

              As high-throughput techniques including proteomics become more accessible to individual laboratories, there is an urgent need for a user-friendly bioinformatics analysis system. Here, we describe FunRich, an open access, standalone functional enrichment and network analysis tool. FunRich is designed to be used by biologists with minimal or no support from computational and database experts. Using FunRich, users can perform functional enrichment analysis on background databases that are integrated from heterogeneous genomic and proteomic resources (>1.5 million annotations). Besides default human specific FunRich database, users can download data from the UniProt database, which currently supports 20 different taxonomies against which enrichment analysis can be performed. Moreover, the users can build their own custom databases and perform the enrichment analysis irrespective of organism. In addition to proteomics datasets, the custom database allows for the tool to be used for genomics, lipidomics and metabolomics datasets. Thus, FunRich allows for complete database customization and thereby permits for the tool to be exploited as a skeleton for enrichment analysis irrespective of the data type or organism used. FunRich (http://www.funrich.org) is user-friendly and provides graphical representation (Venn, pie charts, bar graphs, column, heatmap and doughnuts) of the data with customizable font, scale and color (publication quality).
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                Author and article information

                Contributors
                pws@caltech.edu
                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                13 September 2016
                13 September 2016
                2016
                : 17
                : 1
                : 366
                Affiliations
                HHMI and California Institute of Technology, Division of Biology and Biological Engineering, 1200 E California Blvd, Pasadena, 91125 USA
                Author information
                http://orcid.org/0000-0002-7699-0173
                Article
                1229
                10.1186/s12859-016-1229-9
                5020436
                27618863
                b408e293-acd8-40a5-b2d6-34509c8666c6
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 April 2016
                : 26 August 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award ID: 047-101
                Award Recipient :
                Funded by: National Human Genome Research Institute (US)
                Award ID: HG002223
                Categories
                Methodology Article
                Custom metadata
                © The Author(s) 2016

                Bioinformatics & Computational biology
                gene ontology,anatomy ontology,wormbase,rna-seq,high-throughput biology

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