A human phenome-interactome network of protein complexes implicated in genetic disorders

Kasper Lage, E. Olof Karlberg, Zenia M. Størling, Páll Í Ólason, Anders G. Pedersen, Olga Rigina, Anders M. Hinsby, Zeynep Tümer, Flemming Pociot, Niels Tommerup, Yves Moreau, Søren Brunak*

*Corresponding author af dette arbejde
757 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftNature Biotechnology
Vol/bind25
Udgave nummer3
Sider (fra-til)309-316
Antal sider8
ISSN1087-0156
DOI
StatusUdgivet - mar. 2007
Udgivet eksterntJa

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