Analysis abstract
Nature Biotechnology 25, 309 - 316 (2007)
Published online: 7 March 2007 | doi:10.1038/nbt1295
A human phenome-interactome network of protein complexes implicated in genetic disorders
Kasper Lage1,6, E Olof Karlberg1,6, Zenia M Størling1, Páll Í Ólason1, Anders G Pedersen1, Olga Rigina1, Anders M Hinsby1, Zeynep Tümer2, Flemming Pociot3,4, Niels Tommerup2, Yves Moreau5 & Søren Brunak1
Abstract
We performed a systematic, large-scale analysis of human protein complexes comprising gene products implicated in many different categories of human disease to create a phenome-interactome network. This was done by integrating quality-controlled interactions of human proteins with a validated, computationally derived phenotype similarity score, permitting identification of previously unknown complexes likely to be associated with disease. Using a phenomic ranking of protein complexes linked to human disease, we developed a Bayesian predictor that in 298 of 669 linkage intervals correctly ranks the known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type 2 diabetes and coronary heart disease. Our publicly available draft of protein complexes associated with pathology comprises 506 complexes, which reveal functional relationships between disease-promoting genes that will inform future experimentation.
- Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Building 208, DK-2800 Lyngby, Denmark.
- Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.
- Institute for Clinical Science, University of Lund, SE – 22100 Lund, Sweden.
- Steno Diabetes Center, Niels Steensesvej 2, DK-2820 Gentofte, Denmark.
- Department of Electrical Engineering, Faculty of Engineering, Katholieke Universiteit Leuven, B–3001 Heverlee, Belgium.
- These authors contributed equally to this work.
Correspondence to: Søren Brunak1 e-mail: brunak@cbs.dtu.dk
