Many complex systems display a surprising degree of tolerance against errors. For example, relatively simple organisms grow, persist and reproduce despite drastic pharmaceutical or environmental interventions, an error tolerance attributed to the robustness of the underlying metabolic network [1]. Complex communication networks [2] display a surprising degree of robustness: while key components regularly malfunction, local failures rarely lead to the loss of the global information-carrying ability of the network. The stability of these and other complex systems is often attributed to the redundant wiring of the functional web defined by the systems ’ components. In this paper we demonstrate that error tolerance is not shared by all redundant systems, but it is displayed only by a class of inhomogeneously wired networks, called scale-free networks. We find that scale-free networks, describing a number of systems, such as the World Wide Web (www) [3–5], Internet [6], social networks [7] or a cell [8], display an unexpected degree of robustness, the ability of their nodes to communicate being unaffected by even unrealistically high failure rates. However,

In order to understand the functioning of organisms on the molecular level, we need to know which genes are expressed, when and where in the organism, and to which extent. The regulation of gene expression is achieved through genetic regulatory systems structured by networks of interactions between DNA, RNA, proteins, and small molecules. As most genetic regulatory networks of interest involve many components connected through interlocking positive and negative feedback loops, an intuitive understanding of their dynamics is hard to obtain. As a consequence, formal methods and computer tools for the modeling and simulation of genetic regulatory networks will be indispensable. This paper reviews formalisms that have been employed in mathematical biology and bioinformatics to describe genetic regulatory systems, in particular directed graphs, Bayesian networks, Boolean networks and their generalizations, ordinary and partial differential equations, qualitative differential equations, stochastic equations, and rule-based formalisms. In addition, the paper discusses how these formalisms have been used in the simulation of the behavior of actual regulatory systems. Key words: genetic regulatory networks, mathematical modeling, simulation, computational biology.

In a cell or microorganism the processes that generate mass, energy, information transfer, and cell fate specification are seamlessly integrated through a complex network of various cellular constituents and reactions. However, despite the key role these networks play in sustaining various cellular functions, their large-scale structure is essentially unknown. Here we present the first systematic comparative mathematical analysis of the metabolic networks of 43 organisms representing all three domains of life. We show that, despite significant variances in their individual constituents and pathways, these metabolic networks display the same topologic scaling properties demonstrating striking similarities to the inherent organization of complex non-biological systems. This suggests that the metabolic organization is not only identical for all living organisms, but complies with the design principles of robust and error-tolerant networks, and may represent a common blueprint for the large-scale organization of interactions among all cellular constituents.

Access to unified datasets of protein and genetic interactions is critical for interrogation of gene/ protein function and analysis of global network properties. BioGRID is a freely accessible database of physical and genetic interactions available at

Monotone systems constitute one of the most important classes of dynamical systems used in mathematical biology modeling. The objective of this paper is to extend the notion of monotonicity to systems with inputs and outputs, a necessary first step in trying to understand interconnections, especially including feedback loops, built up out of monotone components. Basic definitions and theorems are provided, as well as an application to the study of a model of one of the cell's most important subsystems.

In a biological cell, cellular functions and the genetic regulatory apparatus are implemented and controlled by a network of chemical reactions in which regulatory proteins can control genes that produce other regulators, which in turn control other genes. Further, the feedback pathways appear to incorporate switches that result in changes in the dynamic behavior of the cell. This paper describes a hybrid systems approach to modeling the intra-cellular network using continuous di#erential equations to model the feedback mechanisms and mode-switching to describe the changes in the underlying dynamics. We use two case studies to illustrate a modular approach to modeling such networks and describe the architectural and behavioral hierarchy in the underlying models. We describe these models using Charon [2], a language that allows formal description of hybrid systems. We provide preliminary simulation results that demonstrate how our approach can help biologists in their analysis of noisy genetic circuits. Finally we describe our agenda for future work that includes the development of models and simulation for stochastic hybrid systems.

RNA folding from sequences into secondary structures is a simple yet powerful, biophysically grounded model of a genotype-phenotype map in which concepts like plasticity, evolvability, epistasis, and modularity can not only be precisely defined and statistically measured but also reveal simultaneous and profoundly non-independent effects of natural selection. Molecular plasticity is viewed here as the capacity of an RNA sequence to assume a variety of energetically favorable shapes by equilibrating among them at constant temperature. Through simulations based on experimental designs, we study the dynamics of a population of RNA molecules that evolve toward a predefined target shape in a constant environment. Each shape in the plastic repertoire of a sequence contributes to the overall fitness of the sequence in proportion to the time the sequence spends in that shape. Plasticity is costly, since the more shapes a sequence can assume, the less time it spends in any one of the...

Th topology of th proteome map revealed by recent large-scalehrge-scaledA methh ht shh thh th distribution of protein--protein interactions ishdxNG hxNGG4d;GxfiIA with many proteinshotei few edges whes a few ofthG arehedCxC connected.Thn particular topology isshx4I byothA cellular networks,such as metabolic patholic and it hd been suggested to be responsible for th hd mutational htationald displayed by th genome of some organisms. InthG paper we explore a recent model of proteome evolutionthl h been shnd to reproduce many of th features displayed by its real counterparts.Th model is based on gene duplication plus re-wiring of th newly created genes.Th statistical features displayed by th proteome of wellknown organisms are reproduced and suggestthg th overall topology of th protein maps naturally emerges fromth two leading mechngdCG considered by th model.

gene expression

Community is an important attribute of Pocket Switched Networks (PSN), because mobile devices are carried by people who tend to belong to communities. We analysed community structure from mobility traces and used for forwarding algorithms [12], which shows significant impact of community. Here, we propose and evaluate three novel distributed community detection approaches with great potential to detect both static and temporal communities. We find that with suitable configuration of the threshold values, the distributed community detection can approximate their corresponding centralised methods up to 90 % accuracy.