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Multi-layer network modules to identify markers for personalized medication in complex diseases

Objective

The symptoms of complex disease like allergy, obesity and cancer depend on the products of multiple interacting genes. High-throughput techniques have implicated hundreds of genes. There are also considerable individual variations. A clinical implication of this may be inadequate treatment response, which is increasingly recognized as a cause of increased suffering and costs. Ideally, physicians should be able to routinely personalize medication based on a few diagnostic markers. Finding such markers is a formidable challenge. We hypothesize that translational clinical studies based on high-throughput genomics, advanced computing and systems biology may help to identify markers for personalized medication in complex diseases. We organize disease-associated genes in networks that are analyzed in a top-down manner. First, modules of interacting genes with distinct biological functions are identified. Then the modules are dissected to find pathways and finally upstream genes with key regulatory functions. We use bioinformatic methods that were recently described by us in Nature Genetics and Nature Biotechnology. An important focus of this project is to develop these methods to form multi-layer modules that integrate information about disease-associated changes on the DNA, RNA and protein levels. Since these levels interact, studies of the different levels can be interactively used to cross-validate the modules. This involves both genetic and experimental studies, but the ultimate test of the modules will be if they can be used for clinical predictions. For example, changes in RNA expression may be caused by a single nucleotide polymorphism (SNP) in a regulatory region. If so, the corresponding protein is tried as a marker to personalize medication. We have chosen hay fever as a model of complex disease because it is common, well-defined and readily examined in clinical and experimental studies. However, the methods may be generally applicable to complex diseases.

Call for proposal

FP7-HEALTH-2007-B
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Coordinator

Universidad Politécnica de Cataluña
Address
Campus Valla
581 83 Linkoping
Sweden

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Helena Blackert (Ms.)
EU contribution
€ 492 991,20

Participants (5)

THE UNIVERSITY OF TENNESSEE
United States
Address
White Avenue 1534
37996 1529 Knoxville

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
E. Christine Cox (Ms.)
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom
EU contribution
€ 353 640
Address
South Kensington Campus Exhibition Road
SW7 2AZ London

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Michael Robinson (Mr.)
CENIX BIOSCIENCE GMBH
Germany
EU contribution
€ 166 800
Address
Tatzberg 47
01307 Dresden

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Karen Huppertz (Ms.)
GOETEBORGS UNIVERSITET
Sweden
EU contribution
€ 777 537,80
Address
Vasaparken
405 30 Goeteborg

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Margareta Ahlqwist (Dr.)
OSLO UNIVERSITETSSYKEHUS HF
Norway
EU contribution
€ 734 919
Address
Kirkeveien 166 Tarnbygget
0450 Oslo

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Activity type
Higher or Secondary Education Establishments
Administrative Contact
Gunhild Mælandsmo (Prof.)