Detection of Core-Periphery Structure in Networks Using Spectral Methods and Geodesic Paths

We introduce several novel and computationally efficient methods for detecting "core--periphery structure" in networks. Core--periphery structure is a type of mesoscale structure that includes densely-connected core vertices and sparsely-connected peripheral vertices. Core vertices tend to be well-connected both among themselves and to peripheral vertices, which tend not to be well-connected to other vertices. Our first method, which is based on transportation in networks, aggregates information from many geodesic paths in a network and yields a score for each vertex that reflects the likelihood that a vertex is a core vertex. Our second method is based on a low-rank approximation of a network's adjacency matrix, which can often be expressed as a tensor-product matrix. Our third approach uses the bottom eigenvector of the random-walk Laplacian to infer a coreness score and a classification into core and peripheral vertices. We also design an objective function to (1) help classify vertices into core or peripheral vertices and (2) provide a goodness-of-fit criterion for classifications into core versus peripheral vertices. To examine the performance of our methods, we apply our algorithms to both synthetically-generated networks and a variety of networks constructed from real-world data sets.Comment: This article is part of EJAM's December 2016 special issue on "Network Analysis and Modelling" (available at https://www.cambridge.org/core/journals/european-journal-of-applied-mathematics/issue/journal-ejm-volume-27-issue-6/D245C89CABF55DBF573BB412F7651ADB

Universality in protein residue networks

Residue networks representing 595 nonhomologous proteins are studied. These networks exhibit universal topological characteristics as they belong to the topological class of modular networks formed by several highly interconnected clusters separated by topological cavities. There are some networks which tend to deviate from this universality. These networks represent small-size proteins having less than 200 residues. We explain such differences in terms of the domain structure of these proteins. On the other hand, we find that the topological cavities characterizing proteins residue networks match very well with protein binding sites. We then investigate the effect of the cutoff value used in building the residue network. For small cutoff values, less than 5Å, the cavities found are very large corresponding almost to the whole protein surface. On the contrary, for large cutoff value, more than 10.0 Å, only very large cavities are detected and the networks look very homogeneous. These findings are useful for practical purposes as well as for identifying "protein-like" complex networks. Finally, we show that the main topological class of residue networks is not reproduced by random networks growing according to Erdös-Rényi model or the preferential attachment method of Barabási-Albert. However, the Watts-Strogatz (WS) model reproduces very well the topological class as well as other topological properties of residue network. We propose here a more biologically appealing modification of the WS model to describe residue networks

Recent advances in clustering methods for protein interaction networks

The increasing availability of large-scale protein-protein interaction data has made it possible to understand the basic components and organization of cell machinery from the network level. The arising challenge is how to analyze such complex interacting data to reveal the principles of cellular organization, processes and functions. Many studies have shown that clustering protein interaction network is an effective approach for identifying protein complexes or functional modules, which has become a major research topic in systems biology. In this review, recent advances in clustering methods for protein interaction networks will be presented in detail. The predictions of protein functions and interactions based on modules will be covered. Finally, the performance of different clustering methods will be compared and the directions for future research will be discussed

A Special Structural Based Weighted Network Approach for the Analysis of Protein Complexes

The detection and analysis of protein complexes is essential for understanding the functional mechanism and cellular integrity. Recently, several techniques for detecting and analysing protein complexes from Protein–Protein Interaction (PPI) dataset have been developed. Most of those techniques are inefficient in terms of detecting, overlapping complexes, exclusion of attachment protein in complex core, inability to detect inherent structures of underlying complexes, have high false-positive rates and an enrichment analysis. To address these limitations, we introduce a special structural-based weighted network approach for the analysis of protein complexes based on a Weighted Edge, Core-Attachment and Local Modularity structures (WECALM). Experimental results indicate that WECALM performs relatively better than existing algorithms in terms of accuracy, computational time, and p-value. A functional enrichment analysis also shows that WECALM is able to identify a large number of biologically significant protein complexes. Overall, WECALM outperforms other approaches by striking a better balance of accuracy and efficiency in the detection of protein complexes

IDENTIFYING CORE COMPONENTS IN SOFTWARE SYSTEMS

As large software systems are highly complex, they can be difficult for a developer to understand. If a core subset of a software system could be extracted which contains the most important classes and connections of the larger system, studying this core would be useful for efficiently understanding the overall system. In this research we examine research into core/periphery structures in networks, primarily focusing on the use of k-core decomposition. The extracted dependencies of three open source Java software systems provide the inputs, with forty different versions of these systems analyzed in total. We derive inter-class dependencies from these releases and represent them as undirected graphs. We extract the k-core values by recursively pruning the least connected nodes within the networks, leaving an inner core. The resulting coreness values are analyzed against centrality metrics and high-level communities detected by the Louvain method. Both system level and component level evolution of coreness values for these systems are studied. The validity of this approach for identifying software system cores is discussed and analyzed

A survey of statistical network models

Networks are ubiquitous in science and have become a focal point for discussion in everyday life. Formal statistical models for the analysis of network data have emerged as a major topic of interest in diverse areas of study, and most of these involve a form of graphical representation. Probability models on graphs date back to 1959. Along with empirical studies in social psychology and sociology from the 1960s, these early works generated an active network community and a substantial literature in the 1970s. This effort moved into the statistical literature in the late 1970s and 1980s, and the past decade has seen a burgeoning network literature in statistical physics and computer science. The growth of the World Wide Web and the emergence of online networking communities such as Facebook, MySpace, and LinkedIn, and a host of more specialized professional network communities has intensified interest in the study of networks and network data. Our goal in this review is to provide the reader with an entry point to this burgeoning literature. We begin with an overview of the historical development of statistical network modeling and then we introduce a number of examples that have been studied in the network literature. Our subsequent discussion focuses on a number of prominent static and dynamic network models and their interconnections. We emphasize formal model descriptions, and pay special attention to the interpretation of parameters and their estimation. We end with a description of some open problems and challenges for machine learning and statistics.Comment: 96 pages, 14 figures, 333 reference

A Computational Approach to Analyze the Mechanism of Action of the Kinase Inhibitor Bafetinib

Prediction of drug action in human cells is a major challenge in biomedical research. Additionally, there is strong interest in finding new applications for approved drugs and identifying potential side effects. We present a computational strategy to predict mechanisms, risks and potential new domains of drug treatment on the basis of target profiles acquired through chemical proteomics. Functional protein-protein interaction networks that share one biological function are constructed and their crosstalk with the drug is scored regarding function disruption. We apply this procedure to the target profile of the second-generation BCR-ABL inhibitor bafetinib which is in development for the treatment of imatinib-resistant chronic myeloid leukemia. Beside the well known effect on apoptosis, we propose potential treatment of lung cancer and IGF1R expressing blast crisis

Accuracy improvement in protein complex prediction from protein interaction networks by refining cluster overlaps

<p>Abstract</p> <p>Background</p> <p>Recent computational techniques have facilitated analyzing genome-wide protein-protein interaction data for several model organisms. Various graph-clustering algorithms have been applied to protein interaction networks on the genomic scale for predicting the entire set of potential protein complexes. In particular, the density-based clustering algorithms which are able to generate overlapping clusters, i.e. the clusters sharing a set of nodes, are well-suited to protein complex detection because each protein could be a member of multiple complexes. However, their accuracy is still limited because of complex overlap patterns of their output clusters.</p> <p><b>Results</b></p> <p>We present a systematic approach of refining the overlapping clusters identified from protein interaction networks. We have designed novel metrics to assess cluster overlaps: overlap coverage and overlapping consistency. We then propose an overlap refinement algorithm. It takes as input the clusters produced by existing density-based graph-clustering methods and generates a set of refined clusters by parameterizing the metrics. To evaluate protein complex prediction accuracy, we used the <it>f</it>-measure by comparing each refined cluster to known protein complexes. The experimental results with the yeast protein-protein interaction data sets from BioGRID and DIP demonstrate that accuracy on protein complex prediction has increased significantly after refining cluster overlaps.</p> <p><b>Conclusions</b></p> <p>The effectiveness of the proposed cluster overlap refinement approach for protein complex detection has been validated in this study. Analyzing overlaps of the clusters from protein interaction networks is a crucial task for understanding of functional roles of proteins and topological characteristics of the functional systems.</p