We simulated a series of mapping strategies implementing a variety of basic and sophisticated features ( Fig. 1 ; Flowcharts of each strategy are provided in Supplementary  Fig. 1 ). All strategies were evaluated using a statistical model based on naïve Bayes to estimate saturation and coverage of the Drosophila interactome as a function of the number of interaction tests. We programmed this model with the assumption that the fly interactome contains approximately 105 interactions overall, along with estimates for the false positive rate (FPR-the probability that a non-interacting protein pair is reported as interacting) and the false negative rate (FNR-the probability that an interacting pair is reported as noninteracting). Although the magnitudes of these errors are still under debate, previous studies2,5,29,35,36 have reported Y2H error rates of FPR < 1% with FNR in the range 50-80% (note that several of these studies erroneously refer to FDR as FPR). Here, we used 0.2% FPR and 66% FNR.