Schwartz Ariel S, Yu Jingkai, Gardenour Kyle R, Finley Russell L, Ideker Trey
Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Nat Methods. 2009 Jan;6(1):55-61. doi: 10.1038/nmeth.1283. Epub 2008 Dec 14.
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 modeled the cost of interaction-map completion for various experimental designs. We showed that current efforts may require up to 20 independent tests covering each protein pair to approach completion. We explored designs for reducing this cost substantially, including prioritization of protein pairs, probability thresholding and interaction prediction. The best experimental designs lowered cost by fourfold overall and >100-fold in early stages of mapping. We demonstrate the best strategy in an ongoing project in Drosophila melanogaster, in which we mapped 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.
针对许多模式生物和人类的全面蛋白质相互作用图谱绘制项目正在进行中。这些项目的关键一步是估算获得准确完整图谱所需的时间、成本和人员。在此，我们对各种实验设计完成相互作用图谱的成本进行了建模。我们表明，目前的工作可能需要多达20次独立测试来覆盖每一对蛋白质，才能接近完成。我们探索了大幅降低成本的设计方法，包括蛋白质对的优先级排序、概率阈值设定和相互作用预测。最佳实验设计总体上使成本降低了四倍，在图谱绘制的早期阶段降低了100倍以上。我们在一项正在进行的黑腹果蝇项目中展示了最佳策略，在该项目中，我们使用47个微量滴定板绘制了450个高可信度的相互作用，而按照当前设计预计需要数千个板。这项研究为评估相互作用图谱绘制项目的可行性以及未来提高其效率的努力提供了一个框架。
