Module Finding Approaches for Protein Interaction Networks

Module Finding Approaches for Protein Interaction Networks

Tero Aittokallio (University of Turku, Finland)
Copyright: © 2009 |Pages: 19
DOI: 10.4018/978-1-60566-398-2.ch018
OnDemand PDF Download:


This chapter provides an overview of the computational approaches developed for exploring the modular organization of protein interaction networks. A special emphasis is placed on the module finding tools implemented in three freely available software packages, VisANT, Cytoscape and MATISSE, as well as on their biomedical applications. The selected methods are presented in the broader context of module discovery options, ranging from approaches that rely merely on topological properties of the underlying network to those that take into account also other complementary data sources, such as the mRNA levels of the proteins. The author will also highlight some current limitations in the measured network data that should be understood when developing and applying module finding methodology, and discuss some key future trends and promising research directions with potential implications for clinical research.
Chapter Preview


Recent advances in experimental technologies and computational methods have made it possible to measure and predict protein-protein interactions on a global scale (see Chapters I-VI and Shoemaker & Panchenko, 2007a, b). While the large-scale interaction datasets can provide an unprecedented glimpse into the cellular mechanisms underlying the behavior of various biological systems, the increasing sizes and densities of the protein interaction networks available today pose also many challenging computational problems. In particular, the inherent complexity of most biological processes and the large number of possible interactions involved can make it difficult to interpret and mine the interaction networks only by eye, even with the help of sophisticated visualization and layout tools available. Software packages that implement computational tools for more advanced network data mining can facilitate the explorative network analysis by identifying the key players and their interactions that contribute to the cellular processes of interest. This may allow e.g. to pinpoint errors in experimentally or computationally derived interaction links, identify proteins directly involved in the particular process, and to formulate hypotheses for follow-up experiments. It should be realized, however, that even if the rapidly developing complex network theory has successfully been applied to analysis of various social and technological networks, such as the Internet and computer chips, its impact on studying molecular interaction networks is still an emerging area of research and therefore all these methods should be considered as experimental. At the moment, the computational tools are best used together with network visualization and analysis software that enable interactive and fully-controlled mining of the complex protein interaction networks.

One of the most fundamental properties found in many biological networks is their modular organization (Hartwell et al., 1999). Consequently, the decomposition of large networks into a hierarchy of possible overlapping sub-networks (so-called modules) has become a principal analytical approach to deal with the complexity of large cellular networks (Barabási & Oltvai, 2004). In protein interaction networks, a functional module refers to a group of physically connected proteins that work together to carry out a specific cellular function in a particular spatio-temporal context. A large number of computational tools of increasing complexity have recently been developed for investigating the modular organization of interaction networks. These tools cannot only identify whether a given network is modular or not, but also detect the modules and their inter-relationships in the underlying network. By relating the found sub-networks with complementary functional genomics or proteomics data, such as gene expression profiles from genome-wide microarray experiments or protein abundance measurements from mass-spectrometry-based assays, it is also possible to identify a hierarchy of connected groups of components that show coherent expression patterns. Such functionally organized modules cannot only emphasize the biological meaning of the modules discovered, but also allow us to gradually focus on the active subsystems of particular interest (active modules), which can lead to concrete hypotheses about the regulatory mechanisms and pathways most important for the given process (Ideker et al., 2002). Moreover, these modules can subsequently be used in predictive modeling studies, with the aim of suggesting new biological hypotheses, such as unexplored new interactions or the function of individual components, or even distinguishing different biomedical phenotypes (discriminative modules).

Complete Chapter List

Search this Book:
Editorial Advisory Board
Table of Contents
Xiao-Li Li, See-Kiong Ng
Chapter 1
Christian Schönbach
Advances in protein-protein interaction (PPI) detection technology and computational analysis methods have produced numerous PPI networks, whose... Sample PDF
Molecular Biology of Protein-Protein Interactions for Computer Scientists
Chapter 2
Koji Tsuda
In this tutorial chapter, the author reviews basics about frequent pattern mining algorithms, including itemset mining, association rule mining, and... Sample PDF
Data Mining for Biologists
Chapter 3
Tatsuya Akutsu, Morihiro Hayashida
Many methods have been proposed for inference of protein-protein interactions from protein sequence data. This chapter focuses on methods based on... Sample PDF
Domain-Based Prediction and Analysis of Protein-Protein Interactions
Chapter 4
Martin S.R. Paradesi, Doina Caragea, William H. Hsu
This chapter presents applications of machine learning to predicting protein-protein interactions (PPI) in Saccharomyces cerevisiae. Several... Sample PDF
Incorporating Graph Features for Predicting Protein-Protein Interactions
Chapter 5
David La, Daisuke Kihara
This chapter gives a comprehensive introduction of the sequence/structural features that are characteristic of protein- protein interaction sites... Sample PDF
Discovering Protein-Protein Interaction Sites from Sequence and Structure
Chapter 6
Paolo Marcatili, Anna Tramontano
This chapter provides an overview of the current computational methods for PPI network cleansing. The authors first present the issue of identifying... Sample PDF
Network Cleansing: Reliable Interaction Networks
Chapter 7
Hugo Willy
Recent breakthroughs in high throughput experiments to determine protein-protein interaction have generated a vast amount of protein interaction... Sample PDF
Discovering Interaction Motifs from Protein Interaction Networks
Chapter 8
Raymond Wan, Hiroshi Mamitsuka
This chapter examines some of the available techniques for analyzing a protein interaction network (PIN) when depicted as an undirected graph.... Sample PDF
Discovering Network Motifs in Protein Interaction Networks
Chapter 9
Clara Pizzuti, Simona Ester Rombo
In this chapter a survey on the main graph-based clustering techniques proposed in the literature to mine proteinprotein interaction networks (PINs)... Sample PDF
Discovering Protein Complexes in Protein Interaction Networks
Chapter 10
Takashi Makino, Aoife McLysaght
This chapter introduces evolutionary analyses of protein interaction networks and of proteins as components of the networks. The authors show... Sample PDF
Evolutionary Analyses of Protein Interaction Networks
Chapter 11
Kar Leong Tew, Xiao-Li Li
This chapter introduces state-of-the-art computational methods which discover lethal proteins from Protein Interaction Networks (PINs). Lethal... Sample PDF
Discovering Lethal Proteins in Protein Interaction Networks
Chapter 12
Hon Nian Chua, Limsoon Wong
Functional characterization of genes and their protein products is essential to biological and clinical research. Yet, there is still no reliable... Sample PDF
Predicting Protein Functions from Protein Interaction Networks
Chapter 13
Pablo Minguez, Joaquin Dopazo
Here the authors review the state of the art in the use of protein-protein interactions (ppis) within the context of the interpretation of genomic... Sample PDF
Protein Interactions for Functional Genomics
Chapter 14
Xiaoyue Zhao, Lilia M. Iakoucheva, Michael Q. Zhang
Genetic factors play a major role in the etiology of many human diseases. Genome-wide experimental methods produce an increasing number of genes... Sample PDF
Prioritizing Disease Genes and Understanding Disease Pathways
Chapter 15
Smita Mohanty, Shashi Bhushan Pandit, Narayanaswamy Srinivasan
Integration of organism-wide protein interactome data with information on expression of genes, cellular localization of proteins and their functions... Sample PDF
Dynamics of Protein-Protein Interaction Network in Plasmodium Falciparum
Chapter 16
Sirisha Gollapudi, Alex Marshall, Daniel Zadik, Charlie Hodgman
Software for the visualization and analysis of protein-protein interaction (PPI) networks can enable general exploration, as well as providing... Sample PDF
Graphical Analysis and Visualization Tools for Protein Interaction Networks
Chapter 17
Valeria Fionda, Luigi Palopoli
The aim of this chapter is that of analyzing and comparing network querying techniques as applied to protein interaction networks. In the last few... Sample PDF
Network Querying Techniques for PPI Network Comparison
Chapter 18
Tero Aittokallio
This chapter provides an overview of the computational approaches developed for exploring the modular organization of protein interaction networks.... Sample PDF
Module Finding Approaches for Protein Interaction Networks
About the Contributors