Predicting the Fission Yeast Protein Interaction Network

A systems-level understanding of biological processes and information flow requires the
mapping of cellular component interactions, among which protein–protein interactions are particularly
important. Fission yeast (Schizosaccharomyces pombe) is a valuable model organism for which no systematic
protein-interaction data are available. We exploited gene and protein properties, global genome
regulation datasets, and conservation of interactions between budding and fission yeast to predict fission
yeast protein interactions in silico. We have extensively tested our method in three ways: first, by predicting
with 70–80% accuracy a selected high-confidence test set; second, by recapitulating interactions between
members of the well-characterized SAGA co-activator complex; and third, by verifying predicted interactions
of the Cbf11 transcription factor using mass spectrometry of TAP-purified protein complexes. Given
the importance of the pathway in cell physiology and human disease, we explore the predicted subnetworks
centered on the Tor1/2 kinases. Moreover, we predict the histidine kinases Mak1/2/3 to be vital
hubs in the fission yeast stress response network, and we suggest interactors of argonaute 1, the principal
component of the siRNA-mediated gene silencing pathway, lost in budding yeast but preserved in S.
pombe. Of the new high-quality interactions that were discovered after we started this work, 73% were
found in our predictions. Even though any predicted interactome is imperfect, the protein network presented
here can provide a valuable basis to explore biological processes and to guide wet-lab experiments
in fission yeast and beyond. Our predicted protein interactions are freely available through PInt, an online
resource on our website (www.bahlerlab.info/PInt).