Scientists Develop ENDEAVOUR - A Computer Program For Identifying Disease Genes

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Scientists Develop ENDEAVOUR - A Computer Program For Identifying

Disease Genes

http://www.medicalnewstoday.com/medicalnews.php?newsid=42989

Genes are the underlying cause of a large number of disorders. But

identifying and studying these genes more closely is a major

challenge for biotechnologists worldwide. Researchers from ESAT-SCD

(Engineering Sciences) and the Flanders Interuniversity Institute for

Biotechnology (VIB) connected to the Catholic University of Leuven

have now developed ENDEAVOUR: a computer program that compiles and

processes data from a variety of databases and identifies the genes

that play a key role in the origin of a disorder. ENDEAVOUR will

undoubtedly become an indispensable tool for identifying disease

genes. In testing their program, the researchers have succeeded in

identifying a gene that plays a major role in the development

of `Di syndrome'.

Seeing the forest for the trees... Genes play an important role in a

large number of disorders - prime examples are Alzheimer's disease

and cancer. A good understanding of these genes is essential in the

quest for diagnoses and treatments. But identifying these `key genes'

among thousands of genes is an enormous challenge. Years of effort by

scientists all over the world have led to a vast amount of data, but

analyzing it is complex. These days, scientists are not only

concerned with generating new data but also with deciphering the

existing data, and thus being able to see the forest for the trees.

ENDEAVOUR

To decipher these genetic data, scientists have developed the

computer program ENDEAVOUR. 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.

Testing the method

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.

Zebra fish enter the fray

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 Di 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 Di syndrome. This study provided

the ultimate proof that ENDEAVOUR is a very useful tool for

identifying new disease genes.

Identifying genes quickly

ENDEAVOUR can accelerate research into a number of disorders by

providing the tools for rapidly identifying genes that play a role in

the disorders.

Combining forces

Collaboration among several different research groups is not always

easy to achieve, but it does usually lead to significant added value.

The publication resulting from this research clearly demonstrates the

importance of constructive collaboration in arriving at innovative

results. Indeed, this is not the result of a single group's research,

but of the collaboration of four different research groups. The

development and validation of a program such as ENDEAVOUR is possible

only through the combination of a variety of skills and expertise.

Funding

This research has been funded by VIB, IWT, FWO, the Catholic

University of Leuven, and the European Union.

Stein Aerts works with Bassem Hassan who is the head of the

Neurogenetics group in the Department of Human Genetics, under the

direction of Guido (for more info, see:

www.vib.be/Research/EN/Research+Departments/Department+of+Human+Geneti

cs/Bassem+Hassan)

Van Loo works with nen who is the head of the Applied

Human Genomics group in the Department of Human Genetics, under the

direction of Guido (for more info, see:

www.vib.be/Research/EN/Research+Departments/Department+of+Human+Geneti

cs/+nen)

Diether Lambrechts and Sunit Maity work with Carmeliet who is

the head of the Functional Genomics of Cardiovascular and

Neurovascular Biology and Disease group in the Department of

Transgene Technology and Gene Therapy, under the direction of Désiré

Collen (for more info, see:

www.vib.be/Research/EN/Research+Departments/Department+of+Transgene+Te

chnology+and+Gene+Therapy/+Carmeliet)

Bert Coessens and Léon- Tranchevent work with Bart De Moor and

Yves Moreau , heading the Bio-Informatics group of the ESAT-SCD

(Signals and Systems) department of the Catholic University of Leuven

under the direction of Joos Vandewalle (for more info, see:

www.esat.kuleuven.be/~dna/bioi and www.kuleuven.be/symbiosys) This

collaboration combined the forces of ESAT (Catholic University of

Leuven) and three VIB research groups in Leuven: the Neurogenetics

group and the group for Applied Human Genomics in the Department of

Human Genetics, and the Functional Genomics of Cardiovascular and

Neurovascular Biology and Disease group in the Department of

Transgene Technology and Gene Therapy.