Construction of co-complex score matrix for protein complex prediction from AP-MS data

Abstract

Motivation: Protein complexes are of great importance for unraveling the secrets of cellular organization and function. The APMS technique has provided an effective high-throughput screening to directly measure the co-complex relationship among multiple proteins, but its performance suffers from both false positives and false negatives. To computationally predict complexes from APMS data, most existing approaches either required the additional knowledge from known complexes (supervised learning), or had numerous parameters to tune. Method: In this article, we propose a novel unsupervised approach, without relying on the knowledge of existing complexes. Our method probabilistically calculates the affinity between two proteins, where the affinity score is evaluated by a co-complexed score or C2S in brief. In particular, our method measures the log-likelihood ratio of two proteins being co-complexed to being drawn randomly, and we then predict protein complexes by applying hierarchical clustering algorithm on the C2S score matrix. Results: Compared with existing approaches, our approach is computationally efficient and easy to implement. It has just one parameter to set and its value has little effect on the results. It can be applied to different species as long as the AP-MS data are available. Despite its simplicity, it is competitive or superior in performance over many aspects when compared with the state-of-the-art predictions performed by supervised or unsupervised approaches. © The Author(s) 2011. Published by Oxford University Press.