Update of the G2D tool for prioritization of gene candidates to inherited diseases

Abstract

G2D (genes to diseases) is a web resource for prioritizing genes as candidates for inherited diseases. It uses three algorithms based on different prioritization strategies. The input to the server is the genomic region where the user is looking for the disease-causing mutation, plus an additional piece of information depending on the algorithm used. This information can either be the disease phenotype (described as an online Mendelian inheritance in man (OMIM) identifier), one or several genes known or suspected to be associated with the disease (defined by their Entrez Gene identifiers), or a second genomic region that has been linked as well to the disease. In the latter case, the tool uses known or predicted interactions between genes in the two regions extracted from the STRING database. The output in every case is an ordered list of candidate genes in the region of interest. For the first two of the three methods, the candidate genes are first retrieved through sequence homology search, then scored accordingly to the corresponding method. This means that some of them will correspond to well-known characterized genes, and others will overlap with predicted genes, thus providing a wider analysis. G2D is publicly available at http://www.ogic.ca/projects/g2d_2/

Figure 1.

G2D web server interface used to detect genes associated to MIS using the protein-protein method. Top left: the user inputs the coordinates for Locus 1 (1p36-p34) and Locus 2 (1q25) that have been genetically linked to MIS. Top right: G2D displays 20 gene candidates in Locus 1 that code for proteins that interact with proteins encoded by genes found in Locus 2. Bottom: tumor necrosis factor TNFSF4 and its receptor TNFRSF4 are encoded in Locus 2 and Locus 1, respectively, being therefore good candidates; a similar pair of genes (TNFSF8/TNFRSF8) appears as candidate 3.