Software for identifying disease genes

Drawing on various databases, ENDEAVOUR gathers all the data about genes that are known to be connected with a disease or a biological process and integrates these data into a mathematical model. With the aid of this model, scientists study the similarities between the 'known genes' and genes whose biological function is not yet known. ENDEAVOUR then indicates whether these genes might possibly underlie a certain disorder.

ENDEAVOUR has been fine-tuned and tested in the laboratory. The researchers took the data for a number of known genes from the mathematical model and then entered the genes as 'unknown' into ENDEAVOUR. For the majority of the syndromes tested (such as Alzheimer's disease, leukemia, colon cancer, and Parkinson's disease), ENDEAVOUR found the underlying genes and thus proved its validity.

As an extra validation of the program, the researchers used ENDEAVOUR to look for new disease genes that underlie hereditary disorders. Among other things, they wanted to identify a new gene that can be correlated with DiGeorge syndrome − a genetic disorder that affects more than 1 in 4000 newborn children. The infants have deformed features and blood vessel abnormalities in the heart. ENDEAVOUR identified one gene as a possible disease gene: YPEL1.

To confirm this mathematical prediction biologically, the researchers used the zebra fish as model system to replicate the disease. They studied zebra fish that could not produce the zebra fish YPEL1 gene. The embryos of these fish showed several abnormalities that are comparable to the symptoms of DiGeorge syndrome. This study provided the ultimate proof that ENDEAVOUR is a very useful tool for identifying new disease genes.

ENDEAVOUR can accelerate research into a number of disorders by providing the tools for rapidly identifying genes that play a role in the disorders.

ENDEAVOUR can be used via: www.esat.kuleuven.ac.be/endeavour or www.bits.vib.be/endeavour.