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

Lage, Kasper; Karlberg, E. Olof; Storling, Zenia M.; Olason, Pall I.; Pedersen, Anders G.; Rigina, Olga; Hinsby, Anders M.; Tumer, Zeynep; Pociot, Flemming LU and Tommerup, Niels, et al. (2007) In Nature Biotechnology 25(3). p.309-316
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... (More)
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. (Less)
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publication status
published
subject
in
Nature Biotechnology
volume
25
issue
3
pages
309 - 316
publisher
Nature Publishing Group
external identifiers
  • wos:000244748300022
  • scopus:33947095027
ISSN
1546-1696
DOI
10.1038/nbt1295
language
English
LU publication?
yes
id
acef23d0-07cd-486c-93eb-7c7c34110052 (old id 671588)
date added to LUP
2007-12-12 12:04:19
date last changed
2017-11-19 04:08:52
@article{acef23d0-07cd-486c-93eb-7c7c34110052,
  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.},
  author       = {Lage, Kasper and Karlberg, E. Olof and Storling, Zenia M. and Olason, Pall I. and Pedersen, Anders G. and Rigina, Olga and Hinsby, Anders M. and Tumer, Zeynep and Pociot, Flemming and Tommerup, Niels and Moreau, Yves and Brunak, Soren},
  issn         = {1546-1696},
  language     = {eng},
  number       = {3},
  pages        = {309--316},
  publisher    = {Nature Publishing Group},
  series       = {Nature Biotechnology},
  title        = {A human phenome-interactome network of protein complexes implicated in genetic disorders},
  url          = {http://dx.doi.org/10.1038/nbt1295},
  volume       = {25},
  year         = {2007},
}