Benchmarking human protein complexes to investigate drug-related systems and evaluate predicted protein complexes.

Xiaoli Li,Chee-Keong Kwoh,Jie Zheng,Jing-Fei Huang,Min Wu,Qi Yu

doi:10.1371/journal.pone.0053197

Abstract

Protein complexes are key entities to perform cellular functions. Human diseases are also revealed to associate with some specific human protein complexes. In fact, human protein complexes are widely used for protein function annotation, inference of human protein interactome, disease gene prediction, and so on. Therefore, it is highly desired to build an up-to-date catalogue of human complexes to support the research in these applications. Protein complexes from different databases are as expected to be highly redundant. In this paper, we designed a set of concise operations to compile these redundant human complexes and built a comprehensive catalogue called CHPC2012 (Catalogue of Human Protein Complexes). CHPC2012 achieves a higher coverage for proteins and protein complexes than those individual databases. It is also verified to be a set of complexes with high quality as its co-complex protein associations have a high overlap with protein-protein interactions (PPI) in various existing PPI databases. We demonstrated two distinct applications of CHPC2012, that is, investigating the relationship between protein complexes and drug-related systems and evaluating the quality of predicted protein complexes. In particular, CHPC2012 provides more insights into drug development. For instance, proteins involved in multiple complexes (the overlapping proteins) are potential drug targets; the drug-complex network is utilized to investigate multi-target drugs and drug-drug interactions; and the disease-specific complex-drug networks will provide new clues for drug repositioning. With this up-to-date reference set of human protein complexes, we believe that the CHPC2012 catalogue is able to enhance the studies for protein interactions, protein functions, human diseases, drugs, and related fields of research. CHPC2012 complexes can be downloaded from http://www1.i2r.a-star.edu.sg/xlli/CHPC2012/CHPC2012.htm.

Highlights

Protein complexes are a form of quaternary structures that are of great importance for understanding cellular organization and functions
Computational prediction of protein complexes can fill up the map of protein ‘‘complexome’’ and is an interesting topic in bioinformatics. In another application of our CHPC2012 complexes, we evaluate the performance of state-of-the-art computational methods for predicting human protein complexes using CHPC2012 as golden standard
We will evaluate the quality of protein complexes predicted by various computational methods using our CHPC2012

Summary

Introduction

Protein complexes are a form of quaternary structures that are of great importance for understanding cellular organization and functions. They are involved in many essential biological processes, such as the transcription of DNA, the translation of mRNA, signal transduction and other processes. The RNA-Induced Silencing Complex (RISC complex) [1] plays an important role in gene regulation by micro RNAs (miRNA) and in defense against viral infections by incorporating one strand of a small interfering RNA (siRNA) or miRNA Another example is the RNA polymerase II complex [2], which transcribes genetic information into messages for ribosomes to produce proteins. The IkB kinase (IKK complex) is an essential regulator of NF-kB activation while dys-regulated NF-kB signaling will lead to various diseases including cancer, chronic inflammation and neurodegenerative diseases [4]

Methods

Results

Conclusion