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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Kasper Lage
  • E. Olof Karlberg
  • Zenia M. Storling
  • Pall I. Olason
  • Anders G. Pedersen
  • Olga Rigina
  • Anders M. Hinsby
  • Zeynep Tumer
  • Flemming Pociot
  • Niels Tommerup
  • Yves Moreau
  • Soren Brunak
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Clinical Medicine
Original languageEnglish
Pages (from-to)309-316
JournalNature Biotechnology
Volume25
Issue number3
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes