Biological Process Linkage Networks

Dikla Dotan-Cohen,Simon Kasif,Avraham A Melkman,Stan Letovsky,Rodolfo Aramayo

doi:10.1371/journal.pone.0005313

Abstract

BackgroundThe traditional approach to studying complex biological networks is based on the identification of interactions between internal components of signaling or metabolic pathways. By comparison, little is known about interactions between higher order biological systems, such as biological pathways and processes.We propose a methodology for gleaning patterns of interactions between biological processes by analyzing protein-protein interactions, transcriptional co-expression and genetic interactions. At the heart of the methodology are the concept of Linked Processes and the resultant network of biological processes, the Process Linkage Network (PLN).ResultsWe construct, catalogue, and analyze different types of PLNs derived from different data sources and different species. When applied to the Gene Ontology, many of the resulting links connect processes that are distant from each other in the hierarchy, even though the connection makes eminent sense biologically. Some others, however, carry an element of surprise and may reflect mechanisms that are unique to the organism under investigation. In this aspect our method complements the link structure between processes inherent in the Gene Ontology, which by its very nature is species-independent.As a practical application of the linkage of processes we demonstrate that it can be effectively used in protein function prediction, having the power to increase both the coverage and the accuracy of predictions, when carefully integrated into prediction methods.ConclusionsOur approach constitutes a promising new direction towards understanding the higher levels of organization of the cell as a system which should help current efforts to re-engineer ontologies and improve our ability to predict which proteins are involved in specific biological processes.

Highlights

The study of biological systems at different levels of organization is a rapidly emerging area of computational biology
With the aim of helping to decipher this higher order connectivity we propose a new methodology for gleaning patterns of interaction between biological processes, manifested by a significantly enriched web of protein-protein interactions, transcriptional coordination or genetic interactions
At the heart of the methodology described in the paper are the concept of Linked Processes and the resultant new network of biological processes, the Process Linkage Network (PLN), whose nodes correspond to biological process terms in the Gene Ontology (GO) database

Summary

Introduction

The study of biological systems at different levels of organization is a rapidly emerging area of computational biology. At the heart of the methodology described in the paper are the concept of Linked Processes and the resultant new network of biological processes, the Process Linkage Network (PLN), whose nodes correspond to biological process terms in the Gene Ontology (GO) database. Using this methodology and exploiting various experimental data and annotations, we are able to uncover different interactive and cooperative relationships between processes. Many of these linked terms are distant from each other in the GOhierarchy, suggesting perhaps a need to revisit the philosophy to organize biological data as a single taxonomy. At the heart of the methodology are the concept of Linked Processes and the resultant network of biological processes, the Process Linkage Network (PLN)

Methods

Results

Conclusion