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

Nat Biotechnol. 2007 Mar;25(3):309-16. doi: 10.1038/nbt1295.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Databases, Genetic
  • Databases, Protein
  • Genetic Diseases, Inborn
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mutation
  • Phenotype
  • Protein Conformation*
  • Protein Interaction Mapping*
  • Proteins / adverse effects*
  • Proteins / genetics
  • Proteome / genetics*
  • Proteomics*


  • Proteins
  • Proteome