Regardless, mapping the Interactome remains a daunting task. Our study makes it clear that achieving 95% coverage of an interactome requires many more screens than one pass through all pools or over all protein pairs. If complete coverage is to be obtained in the near future, it will be necessary to invoke better strategies for experimental design, technologies reporting fewer false negatives, or both. In terms of experimental design, we have shown that the cost of completion is reduced substantially by careful ordering of pooled screens. In terms of technology, our study underscores the importance of decreasing the FNR or of different assays that provide independent samples of a protein pair. Even if the error rates are lower than assumed here, advanced mapping strategies are still likely to be worthwhile (Suppl. Table 1 ). Here we have used two types of Y2H assay, forward and reverse orientations, to obtain multiple samples which appear largely independent. If the assays were partially dependent, multiple tests might still be worth the cost as long as they were not perfectly correlated (and the dependence could be handled quantitatively using a statistical model). In the present study, the conditional independence assumption leads to a "best-case scenario" or lower-bound on the number of interaction tests that will likely be required to achieve full coverage of an interactome. Further work will be needed to better characterize the relative dependencies among the wide range of other interaction assays that are currently available-if the current assays are highly dependent, then the required number of tests will be greater than was estimated here.