Networks Dynamics



DynAMICS OF biological Networks:

Session Introduction

TANYA Y. BERGER-WOLF[1]

Department of Computer Science, University of Illinois at Chicago

Chicago IL 60607, USA

Teresa M. Przytycka[2]

National Center of Biotechnology Information, NLM, NIH

Bethesda MD 20814, USA

MonA SiNGH [3]

Department of Computer Science, Lewis Sigler Institute for Integrative Genomics

Princeton University, Princeton NJ 08544, USA

In modern physics, all phenomena in the universe are considered to be the results of interactions between particles. Biologists are coming to the same conclusion. From genome products working together in a coordinated fashion in order to realize specific cellular functions to diseases spreading through contacts between individuals, the living world is a conflation of myriads of networks of interacting entities. To analyze this added level of complexity, new areas of research have emerged that focus on understanding the roles of interactions between genes, proteins, and other cell components, as well as between cells and even entire organisms.

Network analysis provides a unifying language to describe relations within complex systems and has played an increasingly important role in understanding biological systems. Over the past decade, computational methods have been developed to infer, analyze, and predict the structure of gene and protein networks. The majority of these approaches have focused on the topology, rather than the dynamics of these networks. Yet most biological networks change temporally, spatially and in a context-dependent manner. Therefore, in addition to a description of these networks as collections of nodes and edges, researchers have began to elucidate dynamic properties of biological networks. In molecular networks, this is frequently obtained by integrating static interactions (such as protein-protein or regulatory interactions) with time- or environment-dependent expression data, protein localization data, or other contextual information.

Understanding cellular dynamics will play a key component in efforts to reverse engineer cellular networks. Gene expression or molecular activity data (such as phophorylation state) collected in different time points or under different conditions can be used to infer direct or indirect connections between genes or gene products and, thus, to infer networks. Such reverse network engineering is increasingly more successful thanks to the accumulating availability of biological data and the development of new computational methods. Moreover, computational methods for inference and analysis of dynamic networks are currently being developed in other domains, such as social networks, and recently some of these approaches for topology reconstruction, identification of clusters, and prediction of dynamic networks are starting to be successfully applied to biological networks.

Uncovering the dynamic nature of cellular networks also has clear impacts in human health and disease, as defects in signaling and regulatory pathways are associated with many serious diseases, such as cancer. This necessitates the development of predictive computational approaches that can be used to model the underlying dynamics of signaling and regulatory networks, and may have important ramifications in drug development and discovery.

The session on Dynamics of Biological Networks brings together scientists working on various aspects of the dynamic nature of biological networks. This year, the session includes an invited talk, six contributed papers, and a panel discussion. The invited speaker, Trey Ideker, will provide his perspective on recent important directions in network and systems biology. The papers selected for presentation address a broad spectrum of problems related to network dynamics.

The first group of papers addresses questions related to the analyses of protein interaction networks. Two papers study protein interaction networks from the perspective of evolutionary dynamics. Gibson and Goldberg present a novel framework for reverse engineering the evolution of protein interaction networks of extant species using phylogenetic gene trees and protein interaction data. Colak, Hormozdiari, Schonhuth, Moser, Holman, Ester and Sahinalp utilize multiple interaction networks across large evolutionary distances to understand the formation of certain patterns in protein interaction networks. The paper by Jin, McCallen, Liu, Xiang, Almaas, and Zhou proposes a method for identifying dynamic modules in PPI networks. While temporal information is not readily available in these networks, the authors propose to infer it from the similarity of expression time series data. They then infer modules from the resulting dynamic networks by identifying connected components that are contiguous in time. The paper by Mitrofanova, Farach-Colton, and Mishra gives an efficient and robust algorithm for extracting from physical interaction networks groups of proteins that work together in the same context as protein complexes.

Gene expression data has been proven to be useful in untangling other aspects related to the dynamics of biological networks. Wang and colleagues give an algorithm for identifying post-translational modulators of transcription factor activity that they utilize to produce a first genome-wide map of the interface between signaling and transcriptional regulatory programs in human B cells. They show that the serine-threonine kinase STK38 emerges as the most pleiotropic signaling protein in this cellular context and then biochemically validate this finding by shRNA-mediated silencing of this kinase, followed by gene expression profile analysis.

Gene expression data have been also utilized in the work of Tamada et al. which combines protein-protein interaction networks with transcriptional networks estimated from drug-response time-course expression data to uncover autocrine pathways that are dynamically regulated by drug response.

In addition to the oral presentations two papers have been selected for presentation in the proceedings. The paper by Palisano et al. shows how to automatically translate a system described using ODEs into a stochastic approach featured by the BlenX language. They then apply their framework to model the yeast cell cycle. The paper of Nakamura et al. demonstrates the potential power of large-scale particle filtering for parameter estimations of in silico biological pathways where time-course measurements of biochemical reactions are available.

The panel will discuss questions related to the opportunities and challenges of analyzing the dynamics of biological networks gleaned from large-scale experimental data. In our tutorial, we hope to touch upon the techniques developed in the field of dynamic network analysis and contemplate how they may be relevant in biological settings. As more temporal, spatial, and contextual data become available for proteins and other cellular macromolecules, we are certain that computational methods for analyses of dynamic networks will become increasingly important. With this session, we hope to encourage computational biologists and bioinformaticians to begin to view networks from a dynamic perspective.

Acknowledgements

We are grateful to those who submitted manuscripts for consideration for inclusion in this session, and we thank the numerous reviewers for their valuable expertise and time throughout the peer review process.

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[1] Work partially supported by NSF CAREER grant IIS-0747369 and NSF grants IIS-0705822 and IIS-0612044

[2] Supported by the Intramural Research Program of the National Institutes of Health and National Library of Medicine

[3] Work partially supported by NSF grant CCF-0542187, NIH grant GM076275 and NIH Center of Excellence grant P50 GM071508

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