Statistical Viewer: a tool to upload and integrate linkage and association data as plots displayed within the Ensembl genome browser

Abstract

Background: To facilitate efficient selection and the prioritization of candidate complex disease susceptibility genes for association analysis, increasingly comprehensive annotation tools are essential to integrate, visualize and analyze vast quantities of disparate data generated by genomic screens, public human genome sequence annotation and ancillary biological databases. We have developed a plug-in package for Ensembl called "Statistical Viewer" that facilitates the analysis of genomic features and annotation in the regions of interest defined by linkage analysis.

Results: Statistical Viewer is an add-on package to the open-source Ensembl Genome Browser and Annotation System that displays disease study-specific linkage and/or association data as 2 dimensional plots in new panels in the context of Ensembl's Contig View and Cyto View pages. An enhanced upload server facilitates the upload of statistical data, as well as additional feature annotation to be displayed in DAS tracts, in the form of Excel Files. The Statistical View panel, drawn directly under the ideogram, illustrates lod score values for markers from a study of interest that are plotted against their position in base pairs. A module called "Get Map" easily converts the genetic locations of markers to genomic coordinates. The graph is placed under the corresponding ideogram features a synchronized vertical sliding selection box that is seamlessly integrated into Ensembl's Contig- and Cyto- View pages to choose the region to be displayed in Ensembl's "Overview" and "Detailed View" panels. To resolve Association and Fine mapping data plots, a "Detailed Statistic View" plot corresponding to the "Detailed View" may be displayed underneath.

Conclusion: Features mapping to regions of linkage are accentuated when Statistic View is used in conjunction with the Distributed Annotation System (DAS) to display supplemental laboratory information such as differentially expressed disease genes in private data tracks. Statistic View is a novel and powerful visual feature that enhances Ensembl's utility as valuable resource for integrative genomic-based approaches to the identification of candidate disease susceptibility genes. At present there are no other tools that provide for the visualization of 2-dimensional plots of quantitative data scores against genomic coordinates in the context of a primary public genome annotation browser.

Figure 1

Contig View featuring Statistic View. Shown is a screen shot depicting a local implementation of Ensembl's contig view page hosted by the Duke Center for Human Genetics, captured using SnagIt 7.0. The figure illustrates the appearance of the Statistic View panel and some of its features in the context of Contig View. It also demonstrates how the selection of a peak can enable the researcher to easily see where linkage data and other features such as potentially unstable tri-nucleotide repeats and gene expression data converge to suggest priority gene for association and sequence analysis.

Figure 2

Cyto View featuring Statistic View. A screen shot of private data hosted at primer.duhs.duke.edu illustrating the integration of Statistic View in the Ensembl CytoView page.

Figure 3

Table structures for the linkage object and the user access database. Part A of the figure shows that the study field serves as the key relating the User Data to the Linkage Data. Also shown are examples (part B) of three data records that define plot coordinates along with other attributes. User databases are created to allow restricted access for uploading data.

Figure 4

Flow chart illustrating the flow of data in Statistic View. A security feature is built in so that the process aborts if the user is not authenticated.