A web tool for finding gene candidates associated with experimentally induced arthritis in the rat

Rat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at . The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information

The bovine QTL viewer: a web accessible database of bovine Quantitative Trait Loci

BACKGROUND: Many important agricultural traits such as weight gain, milk fat content and intramuscular fat (marbling) in cattle are quantitative traits. Most of the information on these traits has not previously been integrated into a genomic context. Without such integration application of these data to agricultural enterprises will remain slow and inefficient. Our goal was to populate a genomic database with data mined from the bovine quantitative trait literature and to make these data available in a genomic context to researchers via a user friendly query interface. DESCRIPTION: The QTL (Quantitative Trait Locus) data and related information for bovine QTL are gathered from published work and from existing databases. An integrated database schema was designed and the database (MySQL) populated with the gathered data. The bovine QTL Viewer was developed for the integration of QTL data available for cattle. The tool consists of an integrated database of bovine QTL and the QTL viewer to display QTL and their chromosomal position. CONCLUSION: We present a web accessible, integrated database of bovine (dairy and beef cattle) QTL for use by animal geneticists. The viewer and database are of general applicability to any livestock species for which there are public QTL data. The viewer can be accessed at

The Rat Genome Database (RGD): developments towards a phenome database

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms

methBLAST and methPrimerDB: web-tools for PCR based methylation analysis

BACKGROUND: DNA methylation plays an important role in development and tumorigenesis by epigenetic modification and silencing of critical genes. The development of PCR-based methylation assays on bisulphite modified DNA heralded a breakthrough in speed and sensitivity for gene methylation analysis. Despite this technological advancement, these approaches require a cumbersome gene by gene primer design and experimental validation. Bisulphite DNA modification results in sequence alterations (all unmethylated cytosines are converted into uracils) and a general sequence complexity reduction as cytosines become underrepresented. Consequently, standard BLAST sequence homology searches cannot be applied to search for specific methylation primers. RESULTS: To address this problem we developed methBLAST, a sequence similarity search program, based on the original BLAST algorithm but querying in silico bisulphite modified genome sequences to evaluate oligonucleotide sequence similarities. Apart from the primer specificity analysis tool, we have also developed a public database termed methPrimerDB for the storage and retrieval of validated PCR based methylation assays. The web interface allows free public access to perform methBLAST searches or database queries and to submit user based information. Database records can be searched by gene symbol, nucleotide sequence, analytical method used, Entrez Gene or methPrimerDB identifier, and submitter's name. Each record contains a link to Entrez Gene and PubMed to retrieve additional information on the gene, its genomic context and the article in which the methylation assay was described. To assure and maintain data integrity and accuracy, the database is linked to other reference databases. Currently, the database contains primer records for the most popular PCR-based methylation analysis methods to study human, mouse and rat epigenetic modifications. methPrimerDB and methBLAST are available at and . CONCLUSION: We have developed two integrated and freely available web-tools for PCR based methylation analysis. methBLAST allows in silico assessment of primer specificity in PCR based methylation assays that can be stored in the methPrimerDB database, which provides a search portal for validated methylation assays

Developing a web accessible integrated database and visualization tool for bovine quantitative trait loci

A quantitative trait locus (QTL) is the location of a gene that affects a trait that is measured on a quantitative (linear) scale. Many important agricultural traits such as weight gain, milk fat content and intramuscular fat in cattle are quantitative traits. There is a need to integrate genomic sequence data with QTL data and to develop an analytical tool to visualize the data. Without integration, application of this data to agricultural enterprise productivity will be slow and inefficient. My thesis presents a web-accessible tool called the Bovine QTL Viewer developed to solve this problem. It consists of an integrated database of bovine QTL and the QTL viewer to view the QTL and their relative chromosomal position. This tool generates dynamic and interactive images and supports research in the field of genomics. For this tool, the data is modeled and the QTL viewer is developed based on the requirements and feedback of experts in the field of bovine genomics

AnimalQTLdb: a livestock QTL database tool set for positional QTL information mining and beyond

The Animal Quantitative Trait Loci (QTL) database (AnimalQTLdb) is designed to house all publicly available QTL data on livestock animal species from which researchers can easily locate and compare QTL within species. The database tools are also added to link the QTL data to other types of genomic information, such as radiation hybrid (RH) maps, finger printed contig (FPC) physical maps, linkage maps and comparative maps to the human genome, etc. Currently, this database contains data on 1287 pig, 630 cattle and 657 chicken QTL, which are dynamically linked to respective RH, FPC and human comparative maps. We plan to apply the tool to other animal species, and add more structural genome information for alignment, in an attempt to aid comparative structural genome studies ()