A human phenome-interactome network of protein complexes implicated in genetic disorders.
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.
Lage
Kasper
K
Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Building 208, DK-2800 Lyngby, Denmark.
Karlberg
E Olof
EO
Størling
Zenia M
ZM
Olason
Páll I
PI
Pedersen
Anders G
AG
Rigina
Olga
O
Hinsby
Anders M
AM
Tümer
Zeynep
Z
Pociot
Flemming
F
Tommerup
Niels
N
Moreau
Yves
Y
Brunak
Søren
S
D001499:Bayes Theorem; D030541:Databases, Genetic; D030562:Databases, Protein; D030342:Genetic Diseases, Inborn; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000009:adverse effects* / Q000235:genetics; D020543:Proteome / Q000235:genetics*; D040901:Proteomics
D011506:Proteins; D020543:Proteome