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Researchers compile 'molecular manual' for 100s of inherited diseases

First catalog of tissue-specific changes could improve understanding, help treatment

An international research team has compiled the first catalogue of tissue-specific pathologies underlying hundreds of inherited diseases. These results provide information that may help treat conditions such as breast cancer, Parkinson's disease, heart disease and autism.

The report from scientists at the Technical University of Denmark and Massachusetts General Hospital (MGH) will appear in the Proceedings of the National Academy of Sciences and has been published online.

"Disease processes in humans are far from being exhaustively understood and characterized, in part because they are the result of complex interactions between many molecules that may take place only in specific tissues or organs. Experiments to directly study these interactions in human patients would not be possible, which limits our understanding of how diseases arise and which molecules and genes are involved," says co-lead author Kasper Lage, PhD, of the MGH Pediatric Surgical Research Laboratories.

Co-lead author Niclas Tue Hansen, MSc, from the Center for Biological Sequence Analysis, Technical University of Denmark, adds, "We let supercomputers model biological processes in tissues across the human organism, based on the knowledge from millions of already published articles. In this way we were able to create an extensive map of the interactions of molecules in many diseases – a sort of molecular manual – without carrying out experiments in patients." The catalogue, which is freely available on the Center for Biological Sequence Analysis web page ( ), should help physicians and researchers investigating many serious disorders, he notes.

"It has been extremely exciting to integrate the disease expertise of researchers at MGH and Harvard Medical School with the work of leading systems biologists at the Technical University of Denmark," says Patricia Donahoe, MD, director of Pediatric Surgery Research at MGH and co-corresponding author of the PNAS study.

"This current study brought together the strengths of both teams and resulted in a unique way of analyzing inherited diseases. Our findings have the potential to advance the knowledge of pathways, genes and proteins involved in hundreds of human disorders and perhaps contribute to better treatment strategies for some of these serious diseases," Donahoe is the Marshall K. Bartlett Professor of Surgery at Harvard Medical School.

Sue McGreevey | EurekAlert!
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