Cost effective strategies for completing the Interactome

Comprehensive protein interaction mapping projects are underway for many model species and humans. A key step in these projects is estimating the time, cost, and personnel required for obtaining an accurate and complete map. Here, we model the cost of interaction map completion across a spectrum of experimental designs. We show that current efforts may require up to 20 independent tests covering each protein pair to approach completion. We explore designs for reducing this cost substantially, including prioritization of protein pairs, probability thresholding, and interaction prediction. The best designs lower cost by four-fold overall and >100-fold in early stages of mapping. We demonstrate the best strategy in an ongoing project in Drosophila, in which we map 450 high-confidence interactions using 47 microtiter plates, versus thousands of plates expected using current designs. This study provides a framework for assessing the feasibility of interaction mapping projects and for future efforts to increase their efficiency.