The Reactome Knowledgebase (www.reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression pattern surveys or somatic mutation catalogues from tumour cells. Over the last two years we redeveloped major components of the Reactome web interface to improve usability, responsiveness and data visualization. A new pathway diagram viewer provides a faster, clearer interface and smooth zooming from the entire reaction network to the details of individual reactions. Tool performance for analysis of user datasets has been substantially improved, now generating detailed results for genome-wide expression datasets within seconds. The analysis module can now be accessed through a RESTFul interface, facilitating its inclusion in third party applications. A new overview module allows the visualization of analysis results on a genome-wide Reactome pathway hierarchy using a single screen page. The search interface now provides auto-completion as well as a faceted search to narrow result lists efficiently.

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The Reactome Pathway Knowledgebase.

The National Human Genome Research Institute (NHGRI) Catalog of Published Genome-Wide Association Studies (GWAS) Catalog provides a publicly available manually curated collection of published GWAS assaying at least 100000 singlenucleotide polymorphisms (SNPs) and all SNP-trait associations with P <110 5 . The Catalog includes 1751 curated publications of 11912 SNPs. In addition to the SNP-trait association data, the Catalog also publishes a quarterly diagram of all SNP-trait associations mapped to the SNPs’ chromosomal locations. The Catalog can be accessed via a tabular web interface, via a dynamic visualization on the human karyotype, as a downloadable tab-delimited file and as an OWL knowledge base. This article presents a number of recent improvements to the Catalog, including novel ways for users to interact with the Catalog and changes to the curation infrastructure.

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The NHGRI GWAS Catalog, a curated resource of SNP-trait associations

Ontologies tend to be found everywhere. They are viewed as the silver bullet for many applications, such as database integration, peer-to-peer systems, e-commerce, semantic web services, or social networks. However, in open or evolving systems, such as the semantic web, different parties would, in general, adopt different ontologies. Thus, merely using ontologies, like using XML, does not reduce heterogeneity: it just raises heterogeneity problems to a higher level. Euzenat and Shvaikos book is devoted to ontology matching as a solution to the semantic heterogeneity problem faced by computer systems. Ontology matching aims at finding correspondences between semantically related entities of different ontologies. These correspondences may stand for equivalence as well as other relations, such as consequence, subsumption, or disjointness, between ontology entities. Many different matching solutions have been proposed so far from various viewpoints, e.g., databases, information systems, and artificial intelligence. The second edition of Ontology Matching has been thoroughly revised and updated to reflect the most recent advances in this quickly developing area, which resulted in more than 150 pages of new content. In particular, the book includes a new chapter dedicated to the methodology for performing ontology matching. It also covers emerging topics, such as data interlinking, ontology partitioning and pruning, context-based matching, matcher tuning, alignment debugging, and user involvement in matching, to mention a few. More than 100 state-of-the-art matching systems and frameworks were reviewed. With Ontology Matching, researchers and practitioners will find a reference book that presents currently available work in a uniform framework. In particular, the work and the techniques presented in this book can be equally applied to database schema matching, catalog integration, XML schema matching and other related problems. The objectives of the book include presenting (i) the state of the art and (ii) the latest research results in ontology matching by providing a systematic and detailed account of matching techniques and matching systems from theoretical, practical and application perspectives.

Ontology Matching

The Biological General Repository for Interaction Datasets (BioGRID) is a public database that archives and disseminates genetic and protein
 interaction data from model organisms and humans
 (http://www.thebiogrid.org). BioGRID currently holds 347 966
 interactions (170 162 genetic, 177 804 protein) curated from both
 high-throughput data sets and individual focused studies, as derived
 from over 23 000 publications in the primary literature. Complete
 coverage of the entire literature is maintained for budding yeast
 (Saccharomyces cerevisiae), fission yeast (Schizosaccharomyces pombe)
 and thale cress (Arabidopsis thaliana), and efforts to expand curation
 across multiple metazoan species are underway. The BioGRID houses 48
 831 human protein interactions that have been curated from 10 247
 publications. Current curation drives are focused on particular areas
 of biology to enable insights into conserved networks and pathways that
 are relevant to human health. The BioGRID 3.0 web interface contains
 new search and display features that enable rapid queries across
 multiple data types and sources. An automated Interaction Management
 System (IMS) is used to prioritize, coordinate and track curation
 across international sites and projects. BioGRID provides interaction
 data to several model organism databases, resources such as Entrez-Gene
 and other interaction meta-databases. The entire BioGRID 3.0 data
 collection may be downloaded in multiple file formats, including PSI MI
 XML. Source code for BioGRID 3.0 is freely available without any
 restrictions.

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The BioGRID Interaction Database: 2011 update

The IEDB, wwwiedborg, contains information on immune epitopes--the molecular targets of adaptive immune responses--curated from the published literature and submitted by National Institutes of Health funded epitope discovery efforts From 2004 to 2012 the IEDB curation of journal articles published since 1960 has caught up to the present day, with >95% of relevant published literature manually curated amounting to more than 15,000 journal articles and more than 704,000 experiments to date The revised curation target since 2012 has been to make recent research findings quickly available in the IEDB and thereby ensure that it continues to be an up-to-date resource Having gathered a comprehensive dataset in the IEDB, a complete redesign of the query and reporting interface has been performed in the IEDB 30 release to improve how end users can access this information in an intuitive and biologically accurate manner We here present this most recent release of the IEDB and describe the user testing procedures as well as the use of external ontologies that have enabled it

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The immune epitope database (IEDB) 3.0

The Disease Ontology (DO) database (http://disease-ontology.org) represents a comprehensive knowledge base of 8043 inherited, developmental and acquired human diseases (DO version 3, revision 2510). The DO web browser has been designed for speed, efficiency and robustness through the use of a graph database. Full-text contextual searching functionality using Lucene allows the querying of name, synonym, definition, DOID and cross-reference (xrefs) with complex Boolean search strings. The DO semantically integrates disease and medical vocabularies through extensive cross mapping and integration of MeSH, ICD, NCI's thesaurus, SNOMED CT and OMIM disease-specific terms and identifiers. The DO is utilized for disease annotation by major biomedical databases (e.g. Array Express, NIF, IEDB), as a standard representation of human disease in biomedical ontologies (e.g. IDO, Cell line ontology, NIFSTD ontology, Experimental Factor Ontology, Influenza Ontology), and as an ontological cross mappings resource between DO, MeSH and OMIM (e.g. GeneWiki). The DO project (http://diseaseontology.sf.net) has been incorporated into open source tools (e.g. Gene Answers, FunDO) to connect gene and disease biomedical data through the lens of human disease. The next iteration of the DO web browser will integrate DO's extended relations and logical definition representation along with these biomedical resource cross-mappings.

Disease Ontology: a backbone for disease semantic integration

Increasing attention has been focused on understanding bacterial biofilms and this growth modality's relation to human disease. In this review we explore the genetic regulation and molecular components involved in biofilm formation and maturation in the context of the Gram-positive cocci, Staphylococcus aureus. In addition, we discuss diseases and host immune responses, along with current therapies associated with S. aureus biofilm infections and prevention strategies.

https://www.tandfonline.com/doi/pdf/10.4161/viru.2.5.17724

Staphylococcus aureus biofilms: properties, regulation, and roles in human disease.

Duchenne muscular dystrophy (DMD) is a fatal X-linked degenerative muscle disease caused by the absence of the microtubule-associated protein dystrophin, which results in a disorganized and denser microtubule cytoskeleton. In addition, mechanotransduction-dependent activation of calcium (Ca 2+ ) and reactive oxygen species (ROS) signaling underpins muscle degeneration in DMD. We show that in muscle from adult mdx mice, a model of DMD, a brief physiologic stretch elicited microtubule-dependent activation of NADPH (reduced-form nicotinamide adenine dinucleotide phosphate) oxidase–dependent production of ROS, termed X-ROS. Further, X-ROS amplified Ca 2+ influx through stretch-activated channels in mdx muscle. Consistent with the importance of the microtubules to the dysfunction in mdx muscle, muscle cells with dense microtubule structure, such as those from adult mdx mice or from young wild-type mice treated with Taxol, showed increased X-ROS production and Ca 2+ influx, whereas cells with a less dense microtubule network, such as young mdx or adult mdx muscle treated with colchicine or nocodazole, showed little ROS production or Ca 2+ influx. In vivo treatments that disrupted the microtubule network or inhibited NADPH oxidase 2 reduced contraction-induced injury in adult mdx mice. Furthermore, transcriptome analysis identified increased expression of X-ROS–related genes in human DMD skeletal muscle. Together, these data show that microtubules are the proximate element responsible for the dysfunction in Ca 2+ and ROS signaling in DMD and could be effective therapeutic targets for intervention.

Microtubules Underlie Dysfunction in Duchenne Muscular Dystrophy

The Human Microbiome Project (HMP) was launched by the National Institutes of Health (NIH) Roadmap for Medical Research and is designed to fuel research into the microbes that live in the various environments of the human body [1]. A major goal of the HMP is to look for correlations between changes in the microbiome and human health. The HMP will generate unprecedented amounts of sequence, annotation and metadata. The analysis of this data requires the ability to collect, integrate, and standardize information of different types and from different sources.

The HMP Data Analysis and Coordination Center (DACC) is the central repository for all HMP data, providing a specialized data management and analysis infrastructure to support the collection, integration and standardization of HMP data and facilitate research. HMP data sets will include over 1000 reference genomes isolated from the human body, as well as 16S ribosomal RNA, and whole metagenome shotgun sequencing of samples collected from multiple body sites and individuals. Successful data integration and standardization will rely on the use of controlled vocabularies, the application of quality control measures, and the development of standard operating procedures. The DACC web portal (http://hmpdacc.org) will provide multiple analysis resources to the research community including data query and visualization, comparative genomics, 16S rRNA analysis, and comparative metagenomic community analysis. Reference genome status and relevant metadata are available through the HMP Project catalog (http://www.hmpdacc.org/project_catalog.html) while annotated HMP reference genomes are provided as part of IMG/HMP (http://www.hmpdacc-resources.org/img_hmp), an HMP specific version of the Integrated Microbial Genomes (IMG) data management and analysis system. IMG/HMP serves as a community resource for comparative analysis of HMP genomes in the comprehensive integrated context of all publicly available microbial genomes.

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Mark J. Mazaitis

Papers

Disease Ontology: a backbone for disease semantic integration

Staphylococcus aureus biofilms: properties, regulation, and roles in human disease.

Microtubules Underlie Dysfunction in Duchenne Muscular Dystrophy

A data analysis and coordination center for the human microbiome project