OrthoDisease is a comprehensive da …
OrthoDisease is a comprehensive database of model organism genes that are orthologous to human disease genes. It was constructed by applying the Inparanoid ortholog detection algorithm to disease genes derived from the Online Mendelian Inheritance in Man database (OMIM).
Over 1000 human genes have been associated with a disease phenotype to date and this number continues to rise on a daily basis. Studying their orthologous counterparts in model organisms assists in the understanding of the role these genes both in normal and pathological situations. A confounding factor in this process is that cross-species comparisons often identify genes which, although highly similar, do not represent a true ortholog and may in fact be functionally dissimilar.
In order to resolve this we plan to identify truly orthologous genes in several model organisms, initially in the worm C. elegans, the fly D. melanogaster, the mustard weed A. thaliana and the yeast S. cerevisiae. They will collect and curate a set of genes that are associated with diseases by extracting and filtering excerpts from the Online Mendelian Inheritance in Man. The sequences of the resulting genes will then be analyzed and scored for orthology using methods previously developed at the Center for Genomics and Bioinformatics, primarily the Inparanoid algorithm. This will yield assignments of orthologs in model organisms, at different levels of confidence, forming the database OrthoDisease.
Orthodisease is constructed primarily using Inparanoid analysis. Inparanoid is a program that automatically detects orthologs (or groups of orthologs) from 2 species. Pairwise comparisons between several model organisms are shown here. The species are derived mainly from the Ensembl resource as well as several submitted organism genomes. The program itself and accessory programs can be downloaded from the Inparanoid website.The algorithm is based on pairwise similarity scores which are by default calculated with NCBI BLAST program.
Inparanoid detects best-best hits between sequences from 2 different species. These are the two seed ORTHOLOGS that form an orthologous group. Other sequences are added to this group if they are closely related to one of the main orthologs. These members of the orthologous group are called IN-PARALOGS. A confidence value is provided for each in-paralog that shows how closely related it is to the main ortholog. Genes/proteins are derived from the Online Inheritence In Man (OMIM) database, both from the "Morbid map", which contains genes directly linked to specific diseases,and from the "Genemap" which contains genes with a know cytogenetic location that have been mentioned in OMIM (but not necessarily in morbidmap).