Abstract
BackgroundMost cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task. Some proteins form stable complexes, while other proteins form transient associations and are part of several complexes at different stages of a cellular process. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step towards unveiling functional and evolutionary mechanisms behind biological networks.ResultsWe propose a new method for identifying and representing overlapping protein complexes (or larger units called functional groups) within a protein interaction network. We develop a graph-theoretical framework that enables automatic construction of such representation. We illustrate the effectiveness of our method by applying it to TNFα/NF-κB and pheromone signaling pathways.ConclusionThe proposed representation helps in understanding the transitions between functional groups and allows for tracking a protein's path through a cascade of functional groups. Therefore, depending on the nature of the network, our representation is capable of elucidating temporal relations between functional groups. Our results show that the proposed method opens a new avenue for the analysis of protein interaction networks.
Highlights
Most cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task
Data on protein complexes are collected from the study of individual systems, and more recently through highthroughput experiments, such as yeast two-hybrid (Y2H) [1,2] and tandem affinity purification followed by mass spectrometry (TAP/MS) [3,4]
One way to represent a set of overlapping functional groups is to construct a graph with nodes representing functional groups and edges representing overlaps, i.e., there exists an edge between two functional groups if and only if they share at least one protein
Summary
Most cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. Some proteins form stable complexes, such as the ribosomal complex that consists of more than 50 proteins and three RNA molecules, while other proteins form transient associations and are part of several complexes at different stages of a cellular process. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step (page number not for citation purposes). Several research groups have systematically applied TAP/MS technology to study protein complexes involved in different signaling pathways [5]
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