Protein Interactions for Functional Genomics

Protein Interactions for Functional Genomics

Pablo Minguez (Centro de Investigación Príncipe Felipe (CIPF), Spain) and Joaquin Dopazo (Centro de Investigación Príncipe Felipe (CIPF), Spain)
Copyright: © 2009 |Pages: 16
DOI: 10.4018/978-1-60566-398-2.ch013
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Abstract

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 experiments. They report the available resources and methodologies used to create a curated compilation of ppis introducing a novel approach to filter interactions. Special attention is paid in the complexity of the topology of the networks formed by proteins (nodes) and pairwise interactions (edges). These networks can be studied using graph theory and a brief introduction to the characterization of biological networks and definitions of the more used network parameters is also given. Also a report on the available resources to perform different modes of functional profiling using ppi data is provided along with a discussion on the approaches that have typically been applied into this context. They also introduce a novel methodology for the evaluation of networks and some examples of its application.
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Introduction

The available data for protein-protein interactions (ppis) has increased enormously in the last few years with the emergence of high-throughput techniques that can report thousands of ppis in a short time span. The most used techniques in this field are: yeast two hybrid (y2h), tandem affinity purification (TAP) and high-throughput Mass Spectrometry techniques (MS). Reviews on these and related methodologies can be found in Drewes and Bouwmeester (2003), Cho et al. (2003), Falk et al. (2007) and Berggard et al. (2007).

The reliability of this data is not exempt of controversy. Studies comparing resulting data from several experiments demonstrate that the overlap between them is not as complete as desirable. This can be due to the fact that some methodologies do not reach the saturation point (Bader & Hogue, 2002) or because of the lack of accuracy and coverage on some of them (von Mering et al., 2002). A conventional large-scale experiment can cover only 3-9% of the total interactome, so limited overlap should be expected (Han et al., 2005). False positives are also a problem: in y2h these represent up to 50% of the total data (Ito et al., 2001; Mrowka et al., 2001). Moreover, there is a bias in the functional categories of the ppis each technique detects, e.g. y2h fails in detecting proteins involved in translation (von Mering et al., 2002).

Beyond discussions about accuracy and coverage of this kind of experiments, the relevance of ppis in the cellular machinery has fostered an unprecedented interest in the exploration of the interactome of model organisms such as Saccharomyces cerevisiae (Uetz et al., 2000; Ito et al., 2001), Drosophila melanogaster (Gio et al., 2003; Formstecher et al., 2005), Caenorhabditis elegans (Li et al., 2004) or human (Stelzl et al., 2005, Rual et al., 2005), just to cite a few examples.

Actually, after years of intensive study, there is a high-quality, literature curated set of ppis free from false positives that probably represents the complete yeast interactome (Reguly et al., 2006). In the case of human, the scenario is still far away from this degree of detail. The estimated size of the human interactome is of 650,000 ppis (Stumpf et al., 2008). None of the public databases contain more than 10% of this number of ppis, and a compilation of all the known ppis would only cover about 10% of the interactions.

The interactome is an abstract scaffold that does not provide information about particular conditions, cell developmental stage or cell type in which a particular ppi occurs (if any). To infer a case-specific interactome it is necessary to integrate other types of data that provide information that allows inferring the active ppis at a particular condition. To achieve this, the transcriptome, defined as the set of transcripts that are expressed at a given moment in a particular cell type, can be used. An integrative study of the interactome filtered by the transcriptome will provide valuable information on the active ppis in a given cell state.

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Dedication
Editorial Advisory Board
Table of Contents
Acknowledgment
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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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About the Contributors