Assigning Confidence Scores to Protein–Protein Interactions

Abstract

Screens for protein–protein interactions using assays like the yeast two-hybrid system have generated volumes of useful data. The protein interactions from these screens have been used to develop a better understanding of the functions of individual proteins, regulatory pathways, molecular machines, and entire biological systems. The value of this data, however, is limited by the inherent frequency of false positives that arise in most protein interaction screens. Appreciable numbers of false positives can crop up in both low-throughput and high-throughput screens, and even in screens that employ stringent criteria for defining a positive. A number of classification systems have been used to help distinguish false positives from biologically relevant true positives. This chapter describes a system for assigning a confidence score to each interaction based on the probability that it is a true positive. Such confidence scores can be used to prioritize interactions for validation. The scores are also useful for network analysis methods that take advantage of probabilistic edge weights. The scoring method does not rely on gold standard datasets of reliable true positives and true negatives, and thus circumvents the challenges associated with obtaining such datasets. Moreover, the scoring method uses data features that are largely assay-independent, making it useful for interactions obtained from a variety of different technologies and screening methods.