Diffusion Component Analysis: Unraveling Functional Topology in Biological Networks

Complex biological systems have been successfully modeled by biochemical and genetic interaction networks, typically gathered from high-throughput (HTP) data. These networks can be used to infer functional relationships between genes or proteins. Using the intuition that the topological role of a gene in a network relates to its biological function, local or diffusion based "guilt-by-association" and graph-theoretic methods have had success in inferring gene functions. Here we seek to improve function prediction by integrating diffusion-based methods with a novel dimensionality reduction technique to overcome the incomplete and noisy nature of network data. In this paper, we introduce diffusion component analysis (DCA), a framework that plugs in a diffusion model and learns a low-dimensional vector representation of each node to encode the topological properties of a network. As a proof of concept, we demonstrate DCA's substantial improvement over state-of-the-art diffusion-based approaches in predicting protein function from molecular interaction networks. Moreover, our DCA framework can integrate multiple networks from heterogeneous sources, consisting of genomic information, biochemical experiments and other resources, to even further improve function prediction. Yet another layer of performance gain is achieved by integrating the DCA framework with support vector machines that take our node vector representations as features. Overall, our DCA framework provides a novel representation of nodes in a network that can be used as a plug-in architecture to other machine learning algorithms to decipher topological properties of and obtain novel insights into interactomes.Comment: RECOMB 201

The evaluation of protein folding rate constant is improved by predicting the folding kinetic order with a SVM-based method

Protein folding is a problem of large interest since it concerns the mechanism by which the genetic information is translated into proteins with well defined three-dimensional (3D) structures and functions. Recently theoretical models have been developed to predict the protein folding rate considering the relationships of the process with tolopological parameters derived from the native (atomic-solved) protein structures. Previous works classified proteins in two different groups exhibiting either a single-exponential or a multi-exponential folding kinetics. It is well known that these two classes of proteins are related to different protein structural features. The increasing number of available experimental kinetic data allows the application to the problem of a machine learning approach, in order to predict the kinetic order of the folding process starting from the experimental data so far collected. This information can be used to improve the prediction of the folding rate. In this work first we describe a support vector machine-based method (SVM-KO) to predict for a given protein the kinetic order of the folding process. Using this method we can classify correctly 78% of the folding mechanisms over a set of 63 experimental data. Secondly we focus on the prediction of the logarithm of the folding rate. This value can be obtained as a linear regression task with a SVM-based method. In this paper we show that linear correlation of the predicted with experimental data can improve when the regression task is computed over two different sets, instead of one, each of them composed by the proteins with a correctly predicted two state or multistate kinetic order.Comment: The paper will be published on WSEAS Transaction on Biology and Biomedicin

Local pre-processing for node classification in networks : application in protein-protein interaction

Network modelling provides an increasingly popular conceptualisation in a wide range of domains, including the analysis of protein structure. Typical approaches to analysis model parameter values at nodes within the network. The spherical locality around a node provides a microenvironment that can be used to characterise an area of a network rather than a particular point within it. Microenvironments that centre on the nodes in a protein chain can be used to quantify parameters that are related to protein functionality. They also permit particular patterns of such parameters in node-centred microenvironments to be used to locate sites of particular interest. This paper evaluates an approach to index generation that seeks to rapidly construct microenvironment data. The results show that index generation performs best when the radius of microenvironments matches the granularity of the index. Results are presented to show that such microenvironments improve the utility of protein chain parameters in classifying the structural characteristics of nodes using both support vector machines and neural networks

Exploring the potential of 3D Zernike descriptors and SVM for protein\u2013protein interface prediction

Abstract Background The correct determination of protein–protein interaction interfaces is important for understanding disease mechanisms and for rational drug design. To date, several computational methods for the prediction of protein interfaces have been developed, but the interface prediction problem is still not fully understood. Experimental evidence suggests that the location of binding sites is imprinted in the protein structure, but there are major differences among the interfaces of the various protein types: the characterising properties can vary a lot depending on the interaction type and function. The selection of an optimal set of features characterising the protein interface and the development of an effective method to represent and capture the complex protein recognition patterns are of paramount importance for this task. Results In this work we investigate the potential of a novel local surface descriptor based on 3D Zernike moments for the interface prediction task. Descriptors invariant to roto-translations are extracted from circular patches of the protein surface enriched with physico-chemical properties from the HQI8 amino acid index set, and are used as samples for a binary classification problem. Support Vector Machines are used as a classifier to distinguish interface local surface patches from non-interface ones. The proposed method was validated on 16 classes of proteins extracted from the Protein–Protein Docking Benchmark 5.0 and compared to other state-of-the-art protein interface predictors (SPPIDER, PrISE and NPS-HomPPI). Conclusions The 3D Zernike descriptors are able to capture the similarity among patterns of physico-chemical and biochemical properties mapped on the protein surface arising from the various spatial arrangements of the underlying residues, and their usage can be easily extended to other sets of amino acid properties. The results suggest that the choice of a proper set of features characterising the protein interface is crucial for the interface prediction task, and that optimality strongly depends on the class of proteins whose interface we want to characterise. We postulate that different protein classes should be treated separately and that it is necessary to identify an optimal set of features for each protein class

A Factor Graph Approach to Automated GO Annotation

As volume of genomic data grows, computational methods become essential for providing a first glimpse onto gene annotations. Automated Gene Ontology (GO) annotation methods based on hierarchical ensemble classification techniques are particularly interesting when interpretability of annotation results is a main concern. In these methods, raw GO-term predictions computed by base binary classifiers are leveraged by checking the consistency of predefined GO relationships. Both formal leveraging strategies, with main focus on annotation precision, and heuristic alternatives, with main focus on scalability issues, have been described in literature. In this contribution, a factor graph approach to the hierarchical ensemble formulation of the automated GO annotation problem is presented. In this formal framework, a core factor graph is first built based on the GO structure and then enriched to take into account the noisy nature of GO-term predictions. Hence, starting from raw GO-term predictions, an iterative message passing algorithm between nodes of the factor graph is used to compute marginal probabilities of target GO-terms. Evaluations on Saccharomyces cerevisiae, Arabidopsis thaliana and Drosophila melanogaster protein sequences from the GO Molecular Function domain showed significant improvements over competing approaches, even when protein sequences were naively characterized by their physicochemical and secondary structure properties or when loose noisy annotation datasets were considered. Based on these promising results and using Arabidopsis thaliana annotation data, we extend our approach to the identification of most promising molecular function annotations for a set of proteins of unknown function in Solanum lycopersicum.Fil: Spetale, Flavio Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Krsticevic, Flavia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Roda, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Bulacio, Pilar Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; Argentin

Event based text mining for integrated network construction

The scientific literature is a rich and challenging data source for research in systems biology, providing numerous interactions between biological entities. Text mining techniques have been increasingly useful to extract such information from the literature in an automatic way, but up to now the main focus of text mining in the systems biology field has been restricted mostly to the discovery of protein-protein interactions. Here, we take this approach one step further, and use machine learning techniques combined with text mining to extract a much wider variety of interactions between biological entities. Each particular interaction type gives rise to a separate network, represented as a graph, all of which can be subsequently combined to yield a so-called integrated network representation. This provides a much broader view on the biological system as a whole, which can then be used in further investigations to analyse specific properties of the networ

A Comparative Analysis of Ensemble Classifiers: Case Studies in Genomics

The combination of multiple classifiers using ensemble methods is increasingly important for making progress in a variety of difficult prediction problems. We present a comparative analysis of several ensemble methods through two case studies in genomics, namely the prediction of genetic interactions and protein functions, to demonstrate their efficacy on real-world datasets and draw useful conclusions about their behavior. These methods include simple aggregation, meta-learning, cluster-based meta-learning, and ensemble selection using heterogeneous classifiers trained on resampled data to improve the diversity of their predictions. We present a detailed analysis of these methods across 4 genomics datasets and find the best of these methods offer statistically significant improvements over the state of the art in their respective domains. In addition, we establish a novel connection between ensemble selection and meta-learning, demonstrating how both of these disparate methods establish a balance between ensemble diversity and performance.Comment: 10 pages, 3 figures, 8 tables, to appear in Proceedings of the 2013 International Conference on Data Minin