The Bait Compatibility Index: Computational Bait Selection for Interaction Proteomics Experiments

Sep. 1, 2010

Protein interaction network maps have been generated for multiple species, making use of large-scale methods such as yeast two-hybrid (Y2H) and affinity purification mass spectrometry (AP-MS). These methods take fundamentally different approaches toward characterizing protein networks, and the resulting data sets provide complementary views of the protein interactome. The specific determinants of the outcome of Y2H and AP-MS experiments, in terms of detection of interacting proteins are, however, poorly understood. Here we show that a statistical model built using sequence- and annotation-based features of bait proteins is able to identify bait features that are significant determinants of the outcome of interaction proteomics experiments. We show that bait features are able to explain in part the disparities observed between Y2H and AP-MS constructed networks and can be used to derive the .bait compatibility index., a numeric score that assesses the compatibility of bait proteins with each technology. Aside from understanding the bias and limitations of interaction proteomics, our approach provides a rational, data-driven method for prioritization of baits for interaction proteomics experiments, an essential requirement for future proteome-wide applications of these technologies.

Figure Comparative analysis of selected Y2H and AP-MS yeast networks. A set of 12 serine/threonine phosphatase baits, tested using Y2H and AP-MS are shown with their associated interaction networks. * Network corresponding to serine/threonine phosphatase 2A (PP2A). The underlying serine/threonine phosphatase network is revealed with AP-MS but not Y2H. Legend: Baits are represented as large nodes, prey as small nodes. In each case, baits annotated as serine/threonine phosphatases or functioning in the peroxisome are outlined in color. Preys outlined in color in represent phosphatase components or proteins with phosphatase regulatory activity. For comparison purposes, AP-MS and Y2H networks have been laid out similarly.

Results from: Saha, S., Kaur, P. Ewing, R.M. J Proteome Research, 9(10): 4972-81, 2010.