Novel Scoring Approach for Protein Co-Purification Data Reveals High Interaction Specificity

摘要

Large-scale protein interaction networks (PINs) have typically been discerned using affinity purification followed by mass spectrometry (AP/MS) and yeast two-hybrid (Y2H) techniques. It is generally recognized that Y2H screens detect direct binary interactions while the AP/MS method captures co-complex associations; however, the latter technique is known to compute the propensity for two proteins to co-purify in an AP/MS data set, thereby allowing us to assess the detected level of interaction specificity by analyzing the corresponding distribution of interaction scores. We find that two recent AP/MS data sets of yeast contain enrichments of specific, or high-scoring, associations as compared to commensurate random profiles, and that curated, direct physical interactions in two prominent data bases have consistently high scores. Our scored interaction data sets are generally more comprehensive than those of previous studies when compared against four diverse high-quality reference sets. Furthermore, we find that our scored data sets are more enriched with curated, direct physical associations than Y2H sets.