EuPathDB: the eukaryotic pathogen database.

EuPathDB (http://eupathdb.org) resources include 11 databases supporting eukaryotic pathogen genomic and functional genomic data, isolate data and phylogenomics. EuPathDB resources are built using the same infrastructure and provide a sophisticated search strategy system enabling complex interrogations of underlying data. Recent advances in EuPathDB resources include the design and implementation of a new data loading workflow, a new database supporting Piroplasmida (i.e. Babesia and Theileria), the addition of large amounts of new data and data types and the incorporation of new analysis tools. New data include genome sequences and annotation, strand-specific RNA-seq data, splice junction predictions (based on RNA-seq), phosphoproteomic data, high-throughput phenotyping data, single nucleotide polymorphism data based on high-throughput sequencing (HTS) and expression quantitative trait loci data. New analysis tools enable users to search for DNA motifs and define genes based on their genomic colocation, view results from searches graphically (i.e. genes mapped to chromosomes or isolates displayed on a map) and analyze data from columns in result tables (word cloud and histogram summaries of column content). The manuscript herein describes updates to EuPathDB since the previous report published in NAR in 2010.

The Strategies WDK: a graphical search interface and web development kit for functional genomics databases.

Web sites associated with the Eukaryotic Pathogen Bioinformatics Resource Center (EuPathDB.org) have recently introduced a graphical user interface, the Strategies WDK, intended to make advanced searching and set and interval operations easy and accessible to all users. With a design guided by usability studies, the system helps motivate researchers to perform dynamic computational experiments and explore relationships across data sets. For example, PlasmoDB users seeking novel therapeutic targets may wish to locate putative enzymes that distinguish pathogens from their hosts, and that are expressed during appropriate developmental stages. When a researcher runs one of the approximately 100 searches available on the site, the search is presented as a first step in a strategy. The strategy is extended by running additional searches, which are combined with set operators (union, intersect or minus), or genomic interval operators (overlap, contains). A graphical display uses Venn diagrams to make the strategy's flow obvious. The interface facilitates interactive adjustment of the component searches with changes propagating forward through the strategy. Users may save their strategies, creating protocols that can be shared with colleagues. The strategy system has now been deployed on all EuPathDB databases, and successfully deployed by other projects. The Strategies WDK uses a configurable MVC architecture that is compatible with most genomics and biological warehouse databases, and is available for download at code.google.com/p/strategies-wdk. Database URL: www.eupathdb.org.

AmoebaDB and MicrosporidiaDB: functional genomic resources for Amoebozoa and Microsporidia species.

AmoebaDB (http://AmoebaDB.org) and MicrosporidiaDB (http://MicrosporidiaDB.org) are new functional genomic databases serving the amoebozoa and microsporidia research communities, respectively. AmoebaDB contains the genomes of three Entamoeba species (E. dispar, E. invadens and E. histolityca) and microarray expression data for E. histolytica. MicrosporidiaDB contains the genomes of Encephalitozoon cuniculi, E. intestinalis and E. bieneusi. The databases belong to the National Institute of Allergy and Infectious Diseases (NIAID) funded EuPathDB (http://EuPathDB.org) Bioinformatics Resource Center family of integrated databases and assume the same architectural and graphical design as other EuPathDB resources such as PlasmoDB and TriTrypDB. Importantly they utilize the graphical strategy builder that affords a database user the ability to ask complex multi-data-type questions with relative ease and versatility. Genomic scale data can be queried based on BLAST searches, annotation keywords and gene ID searches, GO terms, sequence motifs, protein characteristics, phylogenetic relationships and functional data such as transcript (microarray and EST evidence) and protein expression data. Search strategies can be saved within a user's profile for future retrieval and may also be shared with other researchers using a unique strategy web address.

EuPathDB: a portal to eukaryotic pathogen databases.

EuPathDB (http://EuPathDB.org; formerly ApiDB) is an integrated database covering the eukaryotic pathogens of the genera Cryptosporidium, Giardia, Leishmania, Neospora, Plasmodium, Toxoplasma, Trichomonas and Trypanosoma. While each of these groups is supported by a taxon-specific database built upon the same infrastructure, the EuPathDB portal offers an entry point to all these resources, and the opportunity to leverage orthology for searches across genera. The most recent release of EuPathDB includes updates and changes affecting data content, infrastructure and the user interface, improving data access and enhancing the user experience. EuPathDB currently supports more than 80 searches and the recently-implemented 'search strategy' system enables users to construct complex multi-step searches via a graphical interface. Search results are dynamically displayed as the strategy is constructed or modified, and can be downloaded, saved, revised, or shared with other database users.

SynView: a GBrowse-compatible approach to visualizing comparative genome data.

UNLABELLED: We present SynView, a simple and generic approach to dynamically visualize multi-species comparative genome data. It is a light-weight application based on the popular and configurable web-based GBrowse framework. It can be used with a variety of databases and provides the user with a high degree of interactivity. The tool is written in Perl and runs on top of the GBrowse framework. It is in use in the PlasmoDB (http://www.PlasmoDB.org) and the CryptoDB (http://www.CryptoDB.org) projects and can be easily integrated into other cross-species comparative genome projects. AVAILABILITY: The program and instructions are freely available at http://www.ApiDB.org/apps/SynView/ CONTACT: jkissing@uga.edu.

Gene expression profiling of epithelial ovarian tumours correlated with malignant potential.

BACKGROUND: Epithelial ovarian tumours exhibit a range of malignant potential, presenting distinct clinical phenotypes. Improved knowledge of gene expression changes and functional pathways associated with these clinical phenotypes may lead to new treatment targets, markers for early detection and a better understanding of disease progression. RESULTS: Gene expression profiling (Affymetrix, U95Av2) was carried out on 18 ovarian tumours including benign adenomas, borderline adenocarcinomas of low malignant potential and malignant adenocarcinomas. Clustering the expression profiles of samples from patients not treated with chemotherapy prior to surgery effectively classified 92% of samples into their proper histopathological group. Some cancer samples from patients treated with chemotherapy prior to surgery clustered with the benign adenomas. Chemotherapy patients whose tumours exhibited benign-like expression patterns remained disease free for the duration of this study as indicated by continued normal serum CA-125 levels. Statistical analysis identified 163 differentially expressed genes: 61 genes under-expressed in cancer and 102 genes over-expressed in cancer. Profiling the functional categories of co-ordinately expressed genes within this list revealed significant correlation between increased malignant potential and loss of both IGF binding proteins and cell adhesion molecules. Interestingly, in several instances co-ordinately expressed genes sharing biological function also shared chromosomal location. CONCLUSION: Our findings indicate that gene expression profiling can reliably distinguish between benign and malignant ovarian tumours. Expression profiles of samples from patients pre-treated with chemotherapy may be useful in predicting disease free survival and the likelihood of recurrence. Loss of expression of IGF binding proteins as well as specific cell adhesion molecules may be a significant mechanism of disease progression in ovarian cancer. Expression levels in borderline tumours were intermediate between benign adenomas and malignant adenocarcinomas for a significant portion of the differentially expressed genes, suggesting that borderline tumours are a transitional state between benign and malignant tumours. Finally, genes displaying coordinated changes in gene expression were often genetically linked, suggesting that changes in expression for these genes are the consequence of regional duplications, deletions or epigenetic events.

RED-T: utilizing the Ratios of Evolutionary Distances for determination of alternative phylogenetic events.

SUMMARY: RED-T is a Java application for phylogenetic analysis based on a unique method, RED, that utilizes the ratios of evolutionary distances E(d) to distinguish between alternative evolutionary histories. RED-T allows the user to examine if any given experimental gene shares the same evolutionary history as the designated control gene(s). Moreover, the tool detects any differences in evolutionary history and allows the user to examine comparisons of E(d) for a likely explanation. Lateral gene transfer, which may have a significant influence in organismal evolution is one mechanism that could explain the findings of these RED-T analyses. AVAILABILITY: The application is available online at http://www.arches.uga.edu/~whitman/RED.