Identification of protein complexes by comparative analysis of yeast and bacterial protein interaction data.
Mounting evidence shows that many protein complexes are conserved in evolution. Here we use conservation to find complexes that are common to the yeast S. cerevisiae and the bacteria H. pylori. Our analysis combines protein interaction data that are available for each of the two species and orthology information based on protein sequence comparison. We develop a detailed probabilistic model for protein complexes in a single species and a model for the conservation of complexes between two species. Using these models, one can recast the question of finding conserved complexes as a problem of searching for heavy subgraphs in an edge- and node-weighted graph, whose nodes are orthologous protein pairs. We tested this approach on the data currently available for yeast and bacteria and detected 11 significantly conserved complexes. Several of these complexes match very well with prior experimental knowledge on complexes in yeast only and serve for validation of our methodology. The complexes suggest new functions for a variety of uncharacterized proteins. By identifying a conserved complex whose yeast proteins function predominantly in the nuclear pore complex, we propose that the corresponding bacterial proteins function as a coherent cellular membrane transport system. We also compare our results to two alternative methods for detecting complexes and demonstrate that our methodology obtains a much higher specificity.
Sharan
Roded
R
School of Computer Science, Tel-Aviv University, Tel-Aviv 69978, Israel. roded@tau.ac.il
Ideker
Trey
T
Kelley
Brian
B
Shamir
Ron
R
Karp
Richard M
RM
D001426:Bacterial Proteins / Q000378:metabolism*; D030562:Databases, Protein; D016480:Helicobacter pylori / Q000378:metabolism*; D046912:Multiprotein Complexes; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D016415:Sequence Alignment
D001426:Bacterial Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins