New Approaches Of Protein Function Prediction From Protein Interaction Networks

Book Description :

New Approaches of Protein Function Prediction from Protein Interaction Networks contains the critical aspects of PPI network based protein function prediction, including semantically assessing the reliability of PPI data, measuring the functional similarity between proteins, dynamically selecting prediction domains, predicting functions, and establishing corresponding prediction frameworks. Functional annotation of proteins is vital to biological and clinical research and other applications due to the important roles proteins play in various biological processes. Although the functions of some proteins have been annotated via biological experiments, there are still many proteins whose functions are yet to be annotated due to the limitations of existing methods and the high cost of experiments. To overcome experimental limitations, this book helps users understand the computational approaches that have been rapidly developed for protein function prediction. Provides innovative approaches and new developments targeting key issues in protein function prediction Presents heuristic ideas for further research in this challenging area

Book Description :

Proteins perform every function in a cell. With the advent of genome sequencing projects for different organisms, large amounts of DNA and protein sequence data is available, whereas their biological function is still unknown in the most of the cases. Predicting protein function is the most challenging problem in post-genomic era. Using sequence homology, phylogenetic profiles, gene expression data, and function of unknown protein can be predicted. Recently, the large interaction networks constructed from high throughput techniques like Yeast2Hybrid experiments are also used in prediction of protein function. As experimental techniques for detection and validation of protein interactions are time consuming, there is a need for computational methods for this task. Based on the concept that a protein performs similar function like its neighbor in protein interaction network, a method is proposed to predict protein function using protein-protein interaction data.This analysis should enlighten the path for predicting unannotated protein function hence identifying diseases and inventing methods of it's cureness.

Book Description :

The biological interactions of living organisms, and protein-protein interactions in particular, are astonishingly diverse. This comprehensive book provides a broad, thorough and multidisciplinary coverage of its field. It integrates different approaches from bioinformatics, biochemistry, computational analysis and systems biology to offer the reader a comprehensive global view of the diverse data on protein-protein interactions and protein interaction networks.

Book Description :

This thesis describes the development of PINALOG, a protein interaction network alignment method, and its application to the area of protein function prediction and protein complex detection. Protein-protein interactions (PPI) play an important role in the function of biological processes. Advances in high-throughput technology have produced a large amount of protein-protein interaction data, enabling analyses at the system level. Although protein-protein interaction networks (PPINs) vary between species, there are components of them that perform similar biological functions and these are likely to be conserved across species. Comparison of the protein interaction networks from different species yields understanding of the evolution of species, as well as a means to predict protein function and conserved components. An alignment method, PINALOG, has been developed which globally aligns the similar parts of the networks using information from protein sequences, protein functions and network topology in a seed-and-extend framework. The results on human and yeast network alignment revealed conserved subnetworks that are components of similar biological processes such as the proteasome or transcription related processes. The alignments of several pairs of species confirm the superior performance of PINALOG over commonly used methods such as Graemlin and IsoRank in terms of finding a large conserved network as well as detecting biologically meaningful mappings of the proteins in the two aligned species. The alignment method also suggested an approach to perform protein complex prediction by knowledge transfer from one species to another. In addition the implications for function prediction of proteins in the "twilight" zone where there is little or no sequence similarity were explored. A web server for PINALOG was developed to provide users access to the alignment method.

Book Description :

Since the completion of sequencing human genome, uncovering the principles of interactions and the functional roles of proteins has been in the spotlight in this post-genomic era. The interactions between proteins provide insights into the underlying mechanisms of biological processes within a cell. The functions of an unknown protein can be postulated on the basis of its interaction evidence with known proteins. The systematic analysis of protein interaction networks has thus become a primary issue in current Bioinformatics research. A wide range of graph theoretic or statistical approaches have attempted to effectively analyze the protein interaction networks. However, they had a limitation in accuracy and efficiency because of the challenges as following. First, the protein-protein interaction data, generated by large-scale high-throughput experiments, are not reliable. Next, the protein interaction networks are typically structured by complex connectivity.^Finally, each protein performs multiple functions in varying environmental conditions. In this dissertation, I explore the quantitative characterization of protein interaction networks based on their unique features such as small-world phenomenon, scale-free distribution and hierarchical modularity. In particular, I focus on accurate, efficient mining of protein interaction networks for the purpose of identifying functional modules and predicting protein functions. A functional module is defined as a maximal set of proteins that participate in the same function. As a pre-process, the network weighting is applied by the integration of functional knowledge from the Gene Ontology database. The semantic similarity and semantic interactivity measures estimate the interaction reliability, which is assigned to the corresponding edge as a weight.^These weighted interaction networks can facilitate the accurate analysis for functional knowledge discovery. I introduce four different approaches for functional module identification and function prediction. First, in the information flow-based approach, I design a novel information flow model that quantifies the propagation of functional information of a protein over the entire complex network. To efficiently implement this model, I propose a dynamic flow simulation algorithm based on random walks. The flow pattern of a protein, generated by this algorithm, indicates its functional impact on the other proteins. Second, the graph restructuring approach retrieves a protein interaction network into a hub-oriented hierarchical structure based on the new definitions of path strength and centrality. This algorithm thus reveals the hierarchically organized functional modules and hubs.^Next, the association pattern-based approach searches the functional association patterns that frequently occur in a protein interaction network. I apply the frequent sub-graph mining algorithm to the labeled graph that is generated by assigning the set of functions of a protein into the node label. Finally, graph reduction is the technique of simplifying the complex connecting pattern of a protein interaction network. Using the reduced graph, the modularization is performed by the iterative procedure of the minimum weighted cut and node accumulation. The generation of protein-protein interaction data is rapidly proceeding, heightening the demand for advances in computational methods to analyze these complex data sets. The approaches presented in this dissertation employ novel, advanced data-mining techniques to discover valuable functional knowledge hidden in the complex protein interaction networks.^This knowledge can be the underlying bases of practical applications in Biomedical Science, e.g., disease diagnosis and drug development. Currently, explosive amounts of heterogeneous biological data are being produced. Developing effective integration methods for incorporating such data is a promising direction for future research.

Book Description :

Alternative techniques and tools for analyzing biomolecular networks With the recent rapid advances in molecular biology, high-throughput experimental methods have resulted in enormous amounts of data that can be used to study biomolecular networks in living organisms. With this development has come recognition of the fact that a complicated living organism cannot be fully understood by merely analyzing individual components. Rather, it is the interactions of components or biomolecular networks that are ultimately responsible for an organism's form and function. This book addresses the important need for a new set of computational tools to reveal essential biological mechanisms from a systems biology approach. Readers will get comprehensive coverage of analyzing biomolecular networks in cellular systems based on available experimental data with an emphasis on the aspects of network, system, integration, and engineering. Each topic is treated in depth with specific biological problems and novel computational methods: GENE NETWORKS—Transcriptional regulation; reconstruction of gene regulatory networks; and inference of transcriptional regulatory networks PROTEIN INTERACTION NETWORKS—Prediction of protein-protein interactions; topological structure of biomolecular networks; alignment of biomolecular networks; and network-based prediction of protein function METABOLIC NETWORKS AND SIGNALING NETWORKS—Analysis, reconstruction, and applications of metabolic networks; modeling and inference of signaling networks; and other topics and new trends In addition to theoretical results and methods, many computational software tools are referenced and available from the authors' Web sites. Biomolecular Networks is an indispensable reference for researchers and graduate students in bioinformatics, computational biology, systems biology, computer science, and applied mathematics.

Book Description :

The identification and mapping of protein-protein interactions (PPIs) is a major goal in systems biology. Experimental data are currently produced in large scale using a variety of high-throughput assays in yeast or mammalian systems. Analysis of these data using computational tools leads to the construction of large protein interaction networks, which help researchers identify novel protein functions. However, our current view of protein interaction networks is still limited and there is an active field of research trying to further develop this concept to include important processes: the topology of interactions and their changes in real time, the effects of competition for binding to the same protein region, PPI variation due to alternative splicing or post-translational modifications, etc. In particular, a clinically relevant topic for development of the concept of protein interactions networks is the consideration of mutant isoforms, which may be responsible for a pathological condition. Mutations in proteins may result in loss of normal interactions and appearance of novel abnormal interactions that may affect a protein’s function and biological cycle. This Research Topic presents novel findings and recent achievements in the field of protein interaction networks with a focus on disease. Authors describe methods for the identification and quantification of PPIs, the annotation and analysis of networks, considering PPIs and protein complexes formed by mutant proteins associated with pathological conditions or genetic diseases.

Book Description :

Current PPI databases do not offer sophisticated querying interfaces and especially do not integrate existing information about proteins. Current algorithms for PIN analysis use only topological information, while emerging approaches attempt to exploit the biological knowledge related to proteins and kinds of interaction, e.g. protein function, localization, structure, described in Gene Ontology or PDB. The book discusses technologies, standards and databases for, respectively, generating, representing and storing PPI data. It also describes main algorithms and tools for the analysis, comparison and knowledge extraction from PINs. Moreover, some case studies and applications of PINs are also discussed.

Book Description :

Proteins are indispensable players in virtually all biological events. The functions of proteins are coordinated through intricate regulatory networks of transient protein-protein interactions (PPIs). To predict and/or study PPIs, a wide variety of techniques have been developed over the last several decades. Many in vitro and in vivo assays have been implemented to explore the mechanism of these ubiquitous interactions. However, despite significant advances in these experimental approaches, many limitations exist such as false-positives/false-negatives, difficulty in obtaining crystal structures of proteins, challenges in the detection of transient PPI, among others. To overcome these limitations, many computational approaches have been developed which are becoming increasingly widely used to facilitate the investigation of PPIs. This book has gathered an ensemble of experts in the field, in 22 chapters, which have been broadly categorized into Computational Approaches, Experimental Approaches, and Others.

Book Description :

The growing flood of new experimental data generated by genome sequencing has provided an impetus for the development of automated methods for predicting the functions of proteins that have been deduced by sequence analysis and lack experimental characterization. Prediction of Protein Structures, Functions and Interactions presents a comprehensive overview of methods for prediction of protein structure or function, with the emphasis on their availability and possibilities for their combined use. Methods of modeling of individual proteins, prediction of their interactions, and docking of complexes are put in the context of predicting gene ontology (biological process, molecular function, and cellular component) and discussed in the light of their contribution to the emerging field of systems biology. Topics covered include: first steps of protein sequence analysis and structure prediction automated prediction of protein function from sequence template-based prediction of three-dimensional protein structures: fold-recognition and comparative modelling template-free prediction of three-dimensional protein structures quality assessment of protein models prediction of molecular interactions: from small ligands to large protein complexes macromolecular docking integrating prediction of structure, function, and interactions Prediction of Protein Structures, Functions and Interactions focuses on the methods that have performed well in CASPs, and which are constantly developed and maintained, and are freely available to academic researchers either as web servers or programs for local installation. It is an essential guide to the newest, best methods for prediction of protein structure and functions, for researchers and advanced students working in structural bioinformatics, protein chemistry, structural biology and drug discovery.

Book Description :

Abstract: Protein function prediction is a fundamental problem in computational biology. For protein activities described by terms in databases such as the Gene Ontology (GO), this task is typically pursued as a binary classification problem. As a result of an astonishing increase in the available genome-wide protein information, integrating different protein datasets has become a significant opportunity and a major focus to infer functionality. This dissertation contains three novel approaches to integrate popular protein information to classify proteins into functional categories. A probabilistic method, Hierarchical Binomial-Neighborhood (HBN), combining proteins' relational information from the protein-protein interaction (PPI) network, together with the GO hierarchical structure, is proposed first. Results from comparing analogous models on terms from the biological process ontology and genes from the yeast genome show substantial improvement and further analysis illustrates that such an improvement is uniformly consistent with the GO depth. Being aware of the fact that the gene interaction knowledge is still incomplete in most organisms, the second approach we develop is an aggressively integrative probabilistic framework, Probabilistic Hierarchical Inferences for Protein Activity (PHIPA), with improved data usage efficiency, for combining protein relational network, categorical motif and cellular localization information and the GO hierarchy. We implement it on a network extracted from an integrative protein-protein association databases STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). Being based on Nearest-Neighbor, or the "guilt-by-association" counting principle, both HBN and PHIPA use only the local neighborhood information, and are therefore built on local probabilistic models. In contrast, we develop a third approach, a fully Bayesian network-based auto-probit framework encoding the functional similarity influenced by the network topology. We not only show that the auto-probit model works equally well in prediction as the "local" methods, but also demonstrate its capability of producing more potentially interesting protein predictions by taking advantage of GO annotation uncertainty, which is critical in using and improving the GO database but yet has been ignored by most existing methodologies in this context.

Book Description :

The first full survey of statistical, topological, data-mining, and ontology-based methods for analyzing protein-protein interaction networks.

Book Description :

Growth in the pharmaceutical market has slowed down – almost to a standstill. One reason is that governments and other payers are cutting costs in a faltering world economy. But a more fundamental problem is the failure of major companies to discover, develop and market new drugs. Major drugs losing patent protection or being withdrawn from the market are simply not being replaced by new therapies – the pharmaceutical market model is no longer functioning effectively and most pharmaceutical companies are failing to produce the innovation needed for success. This multi-authored new book looks at a vital strategy which can bring innovation to a market in need of new ideas and new products: Systems Biology (SB). Modeling is a significant task of systems biology. SB aims to develop and use efficient algorithms, data structures, visualization and communication tools to orchestrate the integration of large quantities of biological data with the goal of computer modeling. It involves the use of computer simulations of biological systems, such as the networks of metabolites comprise signal transduction pathways and gene regulatory networks to both analyze and visualize the complex connections of these cellular processes. SB involves a series of operational protocols used for performing research, namely a cycle composed of theoretical, analytic or computational modeling to propose specific testable hypotheses about a biological system, experimental validation, and then using the newly acquired quantitative description of cells or cell processes to refine the computational model or theory.

Book Description :

New genomic information has revealed the crucial role that protein-protein interactions (PPIs) play in regulating numerous cellular functions. Aberrant forms of these interactions are common in numerous diseases and thus PPIs have emerged as a vast class of critical drug targets. Despite the importance of PPIs in biology, it has been extremely challenging to convert targets into therapeutics and targeting PPIs had long been considered a very difficult task. However, over the past decade the field has advanced with increasing growth in the number of successful PPI regulators. Protein-Protein Interaction Regulators surveys the latest advances in the structural understanding of PPIs as well as recent developments in modulator discovery.

Book Description :

Abstract: Completed genome sequences from many organisms have revealed many genes with no known function. A critical challenge is the development of methods that will aid in the discovery of the molecular functions of the newly discovered genes, while identifying the biological processes in which these genes participate. Current sequence-based methods frequently fail to annotate gene function accurately. New computational approaches combining genomic, transcriptional and proteomic data generated from high-throughput technologies offer potential routes toward predictions of increased accuracy and greater coverage of unknowns. In this thesis, we describe and evaluate several probabilistic methods for protein function prediction that integrate heterogeneous genome-wide data, such as protein-protein interaction (PPI) data, mRNA expression data, protein domain, and localization information under a Bayesian framework. In a cross validation study in yeast, with the goal of predicting the Gene Ontology "biological process" terms, our integrated method increases recall by 18% over methods that only use PPI data, at 50% precision. We compared prediction accuracies in five different model organisms (human, mouse, fly, worm and yeast). Of the various types of genome-wide data incorporated, we found that PPI data contributes most significantly to the improved precision of predictions in yeast. We also develop a context-specific approach for protein function prediction in order to capture dependencies among the various types of biological information listed above. We found that context-specific methods improve prediction precision in some cases, but can also degrade performance for some predictions. Finally, we developed a method to integrate PPI networks between different species through homology mapping. We predict genes that participate in the insulin signaling pathway. This pathway is highly conserved between human and worm, and of profound biological and medical interest given its roles in diabetes and aging. In a cross validation study, our method which derives PPI relationships from both organisms significantly improved prediction performance over a method that only uses PPI data from either human or worm. We produce a large number of predictions in which a number of cases have reasonable literature support.

Book Description :

​​ ​Using genome sequencing, one can predict possible interactions among proteins. There are very few titles that focus on protein-protein interaction predictions in bacteria. The authors will describe these methods and further highlight its use to predict various biological pathways and complexity of the cellular response to various environmental conditions. Topics include analysis of complex genome-scale protein-protein interaction networks, effects of reference genome selection on prediction accuracy, and genome sequence templates to predict protein function.

Book Description :

LION 3, the Third International Conference on Learning and Intelligent Op- mizatioN, was held during January 14–18 in Trento, Italy. The LION series of conferences provides a platform for researchers who are interested in the int- section of e?cient optimization techniques and learning. It is aimed at exploring the boundaries and uncharted territories between machine learning, arti?cial intelligence, mathematical programming and algorithms for hard optimization problems. The considerable interest in the topics covered by LION was re?ected by the overwhelming number of 86 submissions, which almost doubled the 48 subm- sions received for LION’s second edition in December 2007. As in the ?rst two editions, the submissions to LION 3 could be in three formats: (a) original novel and unpublished work for publication in the post-conference proceedings, (b) extended abstracts of work-in-progressor a position statement, and (c) recently submitted or published journal articles for oral presentations. The 86 subm- sions received include 72, ten, and four articles for categories (a), (b), and (c), respectively.

Book Description :

The rapidly evolving field of protein science has now come to realize the ubiquity and importance of protein-protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of high throughput proteomics to monitor protein-protein interactions at an organism level, we can now safely state that protein-protein interactions are the norm and not the exception. Thus, protein function must be understood in the larger context of the various binding complexes that each protein may form with interacting partners at a given time in the life cycle of a cell. Proteins are now seen as forming sophisticated interaction networks subject to remarkable regulation. The study of these interaction networks and regulatory mechanism, which I would like to term "systems proteomics," is one of the thriving fields of proteomics. The bird-eye view that systems proteomics offers should not however mask the fact that proteins are each characterized by a unique set of physical and chemical properties. In other words, no protein looks and behaves like another. This complicates enormously the design of high-throughput proteomics methods. Unlike genes, which, by and large, display similar physico-chemical behaviors and thus can be easily used in a high throughput mode, proteins are not easily amenable to the same treatment. It is thus important to remind researchers active in the proteomics field the fundamental basis of protein chemistry. This book attempts to bridge the two extreme ends of protein science: on one end, systems proteomics, which describes, at a system level, the intricate connection network that proteins form in a cell, and on the other end, protein chemistry and biophysics, which describe the molecular properties of individual proteins and the structural and thermodynamic basis of their interactions within the network. Bridging the two ends of the spectrum is bioinformatics and computational chemistry. Large data sets created by systems proteomics need to be mined for meaningful information, methods need to be designed and implemented to improve experimental designs, extract signal over noise, and reject artifacts, and predictive methods need to be worked out and put to the test. Computational chemistry faces similar challenges. The prediction of binding thermodynamics of protein-protein interaction is still in its infancy. Proteins are large objects, and simplifying assumptions and shortcuts still need to be applied to make simulations manageable, and this despite exponential progress in computer technology. Finally, the study of proteins impacts directly on human health. It is an obvious statement to say that, for decades, enzymes, receptors, and key regulator proteins have been targeted for drug discovery. However, a recent and exciting development is the exploitation of our knowledge of protein-protein interaction for the design of new pharmaceuticals. This presents particular challenges because protein-protein interfaces are generally shallow and interactions are weak. However, progress is clearly being made and the book seeks to provide examples of successes in this area.

Book Description :

Gene function annotation has been a central question in molecular biology. The importance of computational function prediction is increasing because more and more large scale biological data, including genome sequences, protein structures, protein-protein interaction data, microarray expression data, and mass spectrometry data, are awaiting biological interpretation. Traditionally when a genome is sequenced, function annotation of genes is done by homology search methods, such as BLAST or FASTA. However, since these methods are developed before the genomics era, conventional use of them is not necessarily most suitable for analyzing a large scale data. Therefore we observe emerging development of computational gene function prediction methods, which are targeted to analyze large scale data, and also those which use such omics data as additional source of function prediction. In this book, we overview this emerging exciting field. The authors have been selected from 1) those who develop novel purely computational methods 2) those who develop function prediction methods which use omics data 3) those who maintain and update data base of function annotation of particular model organisms (E. coli), which are frequently referred

Book Description :

This book constitutes the refereed proceedings of the 16th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2012, held in Barcelona, Spain, in April 2012. The 31 revised full papers presented together with 5 keynote lectures were carefully reviewed and selected from 200 submissions. The papers feature current research in all areas of computational molecular biology, including: molecular sequence analysis; recognition of genes and regulatory elements; molecular evolution; protein structure; structural genomics; analysis of gene expression; biological networks; sequencing and genotyping technologies; drug design; probabilistic and combinatorial algorithms; systems biology; computational proteomics; structural and functional genomics; information systems for computational biology and imaging.