Algorithms to Explore the Structure and Evolution of Biological Networks

High-throughput experimental protocols have revealed thousands of relationships amongst genes and proteins under various conditions. These putative associations are being aggressively mined to decipher the structural and functional architecture of the cell. One useful tool for exploring this data has been computational network analysis. In this thesis, we propose a collection of novel algorithms to explore the structure and evolution of large, noisy, and sparsely annotated biological networks. We first introduce two information-theoretic algorithms to extract interesting patterns and modules embedded in large graphs. The first, graph summarization, uses the minimum description length principle to find compressible parts of the graph. The second, VI-Cut, uses the variation of information to non-parametrically find groups of topologically cohesive and similarly annotated nodes in the network. We show that both algorithms find structure in biological data that is consistent with known biological processes, protein complexes, genetic diseases, and operational taxonomic units. We also propose several algorithms to systematically generate an ensemble of near-optimal network clusterings and show how these multiple views can be used together to identify clustering dynamics that any single solution approach would miss. To facilitate the study of ancient networks, we introduce a framework called ``network archaeology'') for reconstructing the node-by-node and edge-by-edge arrival history of a network. Starting with a present-day network, we apply a probabilistic growth model backwards in time to find high-likelihood previous states of the graph. This allows us to explore how interactions and modules may have evolved over time. In experiments with real-world social and biological networks, we find that our algorithms can recover significant features of ancestral networks that have long since disappeared. Our work is motivated by the need to understand large and complex biological systems that are being revealed to us by imperfect data. As data continues to pour in, we believe that computational network analysis will continue to be an essential tool towards this end

Reconstructing the ubiquitin network - cross-talk with other systems and identification of novel functions

A computational model of the yeast Ubiquitin system highlights interesting biological features including functional interactions between components and interplay with other regulatory mechanisms

Reconstructing networks

Complex networks datasets often come with the problem of missing information: interactions data that have not been measured or discovered, may be affected by errors, or are simply hidden because of privacy issues. This Element provides an overview of the ideas, methods and techniques to deal with this problem and that together define the field of network reconstruction. Given the extent of the subject, the authors focus on the inference methods rooted in statistical physics and information theory. The discussion is organized according to the different scales of the reconstruction task, that is, whether the goal is to reconstruct the macroscopic structure of the network, to infer its mesoscale properties, or to predict the individual microscopic connections

Community landscapes: an integrative approach to determine overlapping network module hierarchy, identify key nodes and predict network dynamics

Background: Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult. Methodology/Principal Findings: Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1) determine pervasively overlapping modules with high resolution; (2) uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3) allow the determination of key network nodes and (4) help to predict network dynamics. Conclusions/Significance: The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction.Comment: 25 pages with 6 figures and a Glossary + Supporting Information containing pseudo-codes of all algorithms used, 14 Figures, 5 Tables (with 18 module definitions, 129 different modularization methods, 13 module comparision methods) and 396 references. All algorithms can be downloaded from this web-site: http://www.linkgroup.hu/modules.ph

Reconstructing networks

Complex networks datasets often come with the problem of missing information: interactions data that have not been measured or discovered, may be affected by errors, or are simply hidden because of privacy issues. This Element provides an overview of the ideas, methods and techniques to deal with this problem and that together define the field of network reconstruction. Given the extent of the subject, we shall focus on the inference methods rooted in statistical physics and information theory. The discussion will be organized according to the different scales of the reconstruction task, that is, whether the goal is to reconstruct the macroscopic structure of the network, to infer its mesoscale properties, or to predict the individual microscopic connections.Comment: 107 pages, 25 figure