RESEARCHARTICLE WI-PHI: Aweighted yeast interactome enriched for direct physical interactions

How is the yeast proteome wired? This important question, central in yeast systems biology, remains unanswered in spite of the abundance of protein interaction data from high-throughput experiments. Unfortunately, these large-scale studies show striking discrepancies in their results and coverage such that biologists scrutinizing the “interactome ” are often confounded by a mix of established physical interactions, functional associations, and experimental artifacts. This stim-ulated early attempts to integrate the available information and produce a list of protein interac-tions ranked according to an estimated functional reliability. The recent publication of the results of two large protein interaction experiments and the completion of a comprehensive literature curation effort has more than doubled the available information on the wiring of the yeast pro-teome. This motivates a fresh approach to the compilation of a yeast interactome based purely on evidence of physical interaction. We present a procedure exploiting both heuristic and probabil-istic strategies to draft the yeast interactome taking advantage of various heterogeneous data sources: application of tandem affinity purification coupled to MS (TAP-MS), large-scale yeast two-hybrid studies, and results of small-scale experiments stored in dedicated databases. The end result is WI-PHI, a weighted network encompassing a large majority of yeast proteins