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      Using the Semantic Web for Rapid Integration of WikiPathways with Other Biological Online Data Resources

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          Abstract

          The diversity of online resources storing biological data in different formats provides a challenge for bioinformaticians to integrate and analyse their biological data. The semantic web provides a standard to facilitate knowledge integration using statements built as triples describing a relation between two objects. WikiPathways, an online collaborative pathway resource, is now available in the semantic web through a SPARQL endpoint at http://sparql.wikipathways.org. Having biological pathways in the semantic web allows rapid integration with data from other resources that contain information about elements present in pathways using SPARQL queries. In order to convert WikiPathways content into meaningful triples we developed two new vocabularies that capture the graphical representation and the pathway logic, respectively. Each gene, protein, and metabolite in a given pathway is defined with a standard set of identifiers to support linking to several other biological resources in the semantic web. WikiPathways triples were loaded into the Open PHACTS discovery platform and are available through its Web API ( https://dev.openphacts.org/docs) to be used in various tools for drug development. We combined various semantic web resources with the newly converted WikiPathways content using a variety of SPARQL query types and third-party resources, such as the Open PHACTS API. The ability to use pathway information to form new links across diverse biological data highlights the utility of integrating WikiPathways in the semantic web.

          Author Summary

          WikiPathways is a crowd-sourced online platform for biological pathways. It is based on the same underlying platform as Wikipedia. Pathways are saved as graphical images embedded in a set of meta data elements (i.e. references, list of pathways elements, and context annotations). Pathways are used as proxies of biological knowledge in their role as descriptors of processes. Yet integrating these hubs of biological knowledge with other biological data resources remains challenging due to a cacophony of file formats, identifier systems, and hidden content. We show the application of the semantic web to enable a straightforward integration of heterogeneous biological data sources. We have taken high-quality pathways from a curated set from WikiPathways and converted the content into a data format native to the semantic web. Here, data is expressed as a set of statements where the statements are built upon a set of web addresses. Given the results, we successfully integrated external resources (e.g., EBI Expression Atlas) and pathway content with a single query .

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          The Systems Biology Graphical Notation.

          Circuit diagrams and Unified Modeling Language diagrams are just two examples of standard visual languages that help accelerate work by promoting regularity, removing ambiguity and enabling software tool support for communication of complex information. Ironically, despite having one of the highest ratios of graphical to textual information, biology still lacks standard graphical notations. The recent deluge of biological knowledge makes addressing this deficit a pressing concern. Toward this goal, we present the Systems Biology Graphical Notation (SBGN), a visual language developed by a community of biochemists, modelers and computer scientists. SBGN consists of three complementary languages: process diagram, entity relationship diagram and activity flow diagram. Together they enable scientists to represent networks of biochemical interactions in a standard, unambiguous way. We believe that SBGN will foster efficient and accurate representation, visualization, storage, exchange and reuse of information on all kinds of biological knowledge, from gene regulation, to metabolism, to cellular signaling.
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            WikiPathways: building research communities on biological pathways

            Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further.
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              Presenting and exploring biological pathways with PathVisio

              Background Biological pathways are a useful abstraction of biological concepts, and software tools to deal with pathway diagrams can help biological research. PathVisio is a new visualization tool for biological pathways that mimics the popular GenMAPP tool with a completely new Java implementation that allows better integration with other open source projects. The GenMAPP MAPP file format is replaced by GPML, a new XML file format that provides seamless exchange of graphical pathway information among multiple programs. Results PathVisio can be combined with other bioinformatics tools to open up three possible uses: visual compilation of biological knowledge, interpretation of high-throughput expression datasets, and computational augmentation of pathways with interaction information. PathVisio is open source software and available at . Conclusion PathVisio is a graphical editor for biological pathways, with flexibility and ease of use as primary goals.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Comput Biol
                PLoS Comput. Biol
                plos
                ploscomp
                PLoS Computational Biology
                Public Library of Science (San Francisco, CA USA )
                1553-734X
                1553-7358
                June 2016
                23 June 2016
                : 12
                : 6
                : e1004989
                Affiliations
                [1 ]Department of Bioinformatics - BiGCaT, Maastricht University, Maastricht, The Netherlands
                [2 ]Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands
                [3 ]Gladstone Institutes, San Francisco, California, United States of America
                Hellas, GREECE
                Author notes

                The authors have declared that no competing interests exist.

                Wrote the paper: AW MK CTE ARP. Designed the queries queries and use cases: AW MK AR RM ELW.

                Author information
                http://orcid.org/0000-0002-7699-8191
                http://orcid.org/0000-0002-4693-0591
                http://orcid.org/0000-0003-3477-7443
                http://orcid.org/0000-0001-7542-0286
                http://orcid.org/0000-0002-5301-3142
                Article
                PCOMPBIOL-D-16-00251
                10.1371/journal.pcbi.1004989
                4918977
                27336457
                a45363d1-d246-4e35-8077-acf909360283
                © 2016 Waagmeester et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 February 2016
                : 17 May 2016
                Page count
                Figures: 2, Tables: 2, Pages: 11
                Funding
                Funded by: Innovative Medicines Initiative
                Award ID: no115191
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01-GM100039
                Award Recipient :
                This work was supported by: Innovative Medicines Initiatives Joint Undertaking under grant agreement no115191 ( http://www.imi.europa.eu/content/open-phacts); and NIH National Institute for General Medical Sciences (R01-GM100039) ( https://www.nigms.nih.gov/Research/Pages/default.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Social Sciences
                Linguistics
                Semantics
                Computer and Information Sciences
                Data Visualization
                Physical Sciences
                Chemistry
                Chemical Elements
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Protein Metabolism
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolic Pathways
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolic Processes
                Glycolysis
                Biology and Life Sciences
                Genetics
                Gene Expression
                Custom metadata
                All files are available for download at http://rdf.wikipathways.org. The data are also accessible through SPARQL queries at http://sparql.wikipathways.org or through REST-calls at https://dev.openphacts.org/docs.

                Quantitative & Systems biology
                Quantitative & Systems biology

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