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

Kasper Lage Hansen, Erik, Olof, Linnart Karlberg, Zenia, Marian Størling, Páll Ísólfur Ólason, Anders Gorm Pedersen, Olga Rigina, Anders Mørkeberg Hinsby, Zeynep Tumer, Flemming Pociot, Niels Tommerup, Yves Moreau, Søren Brunak

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    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.
    Original languageEnglish
    JournalNature Biotechnology
    Issue number3
    Pages (from-to)309-16
    Publication statusPublished - 2007

    Cite this

    Hansen, K. L., Karlberg, E. O. L., Størling, Z. M., Ólason, P. Í., Pedersen, A. G., Rigina, O., Hinsby, A. M., Tumer, Z., Pociot, F., Tommerup, N., Moreau, Y., & Brunak, S. (2007). A human phenome-interactome network of protein complexes implicated in genetic disorders. Nature Biotechnology, 25(3), 309-16. https://doi.org/10.1038/nbt1295