A two-step framework for inferring direct protein-protein interaction network from AP-MS data

Abstract

Background: Affinity purification-mass spectrometry (AP-MS) has been widely used for generating bait-prey data sets so as to identify underlying protein-protein interactions and protein complexes. However, the AP-MS data sets in terms of bait-prey pairs are highly noisy, where candidate pairs contain many false positives. Recently, numerous computational methods have been developed to identify genuine interactions from AP-MS data sets. However, most of these methods aim at removing false positives that contain contaminants, ignoring the distinction between direct interactions and indirect interactions. Results: In this paper, we present an initialization-and-refinement framework for inferring direct PPI networks from AP-MS data, in which an initial network is first generated with existing scoring methods and then a refined network is constructed by the application of indirect association removal methods. Experimental results on several real AP-MS data sets show that our method is capable of identifying more direct interactions than traditional scoring methods. Conclusions: The proposed framework is sufficiently general to incorporate any feasible methods in each step so as to have potential for handling different types of AP-MS data in the future applications.