Source: Tarassov et al (2008). An in Vivo Map of the Yeast Protein Interactome. Science 320:1465-70.
This paper is interesting in the sense that protein interactions are assayed in vivo and in the context of living cells. The method is quite interesting with room for extensive future tweaking. The authors fuse the proteins to bait and prey fragments of murine dihydrofolate reductase (mDHFR). Upon forming an interaction between the two proteins, mDHFR forms a functional enzyme enabling the cell to grow in the presence of methotrexate (see figure below).
The authors succeed in fusing F[1,2] to 75% of MATa ORFs and 83% of MATalpha (total coverageof 93%). Then they mate these strains in a pairwise set-up and record the growth in the presence of methotrexate as a proxy for interaction between proteins. I haven't gone through their results carefully but it seems like they do capture most of the known gold standard datasets. This was a fun read, congratulations to the authors for their hard work in getting all these fusions....
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