A human phenome-interactome network of protein complexes implicated in genetic disorders
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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A human phenome-interactome network of protein complexes implicated in genetic disorders. / Lage, Kasper; Karlberg, E Olof; Størling, Zenia M; Olason, Páll I; Pedersen, Anders G; Rigina, Olga; Hinsby, Anders M; Tümer, Zeynep; Pociot, Flemming; Tommerup, Niels; Moreau, Yves; Brunak, Søren.
I: Nature Biotechnology, Bind 25, Nr. 3, 2007, s. 309-16.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A human phenome-interactome network of protein complexes implicated in genetic disorders
AU - Lage, Kasper
AU - Karlberg, E Olof
AU - Størling, Zenia M
AU - Olason, Páll I
AU - Pedersen, Anders G
AU - Rigina, Olga
AU - Hinsby, Anders M
AU - Tümer, Zeynep
AU - Pociot, Flemming
AU - Tommerup, Niels
AU - Moreau, Yves
AU - Brunak, Søren
N1 - Keywords: Bayes Theorem; Databases, Genetic; Databases, Protein; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Humans; Mutation; Phenotype; Protein Conformation; Protein Interaction Mapping; Proteins; Proteome; Proteomics
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1038/nbt1295
DO - 10.1038/nbt1295
M3 - Journal article
C2 - 17344885
VL - 25
SP - 309
EP - 316
JO - Nature Biotechnology
JF - Nature Biotechnology
SN - 1087-0156
IS - 3
ER -
ID: 10795429