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5,100
Fold-Hopf Bursting in a Model for Calcium Signal Transduction
q-bio.MN
We study a recent model for calcium signal transduction. This model displays spiking, bursting and chaotic oscillations in accordance with experimental results. We calculate bifurcation diagrams and study the bursting behaviour in detail. This behaviour is classified according to the dynamics of separated slow and fast...
biology
5,101
Communication on the letter: "Evolutionary Conservation of Motif Constituents in the Yeast Protein Interaction Network."
q-bio.MN
Former work on an application of order-disorder theory is recalled as a vehicle to add further development and significance to the recent paper on motifs in protein interactions.
biology
5,102
Enhancement of the stability of genetic switches by overlapping upstream regulatory domains
q-bio.MN
We study genetic switches formed from pairs of mutually repressing operons. The switch stability is characterised by a well defined lifetime which grows sub-exponentially with the number of copies of the most-expressed transcription factor, in the regime accessible by our numerical simulations. The stability can be mar...
biology
5,103
The topology of the regulatory interactions predics the expression pattern of the segment polarity genes in Drosophila melanogaster
q-bio.MN
Expression of the Drosophila segment polarity genes is initiated by a prepattern of pair-rule gene products and maintained by a network of regulatory interactions throughout several stages of embryonic development. Analysis of a model of gene interactions based on differential equations showed that wild-type expression...
biology
5,104
Homogeneous and Scalable Gene Expression Regulatory Networks with Random Layouts of Switching Parameters
q-bio.MN
We consider a model of large regulatory gene expression networks where the thresholds activating the sigmoidal interactions between genes and the signs of these interactions are shuffled randomly. Such an approach allows for a qualitative understanding of network dynamics in a lack of empirical data concerning the larg...
biology
5,105
Toy Models and Statistical Mechanics of Subgraphs and Motifs of Genetic and Protein Networks
q-bio.MN
Theoretical physics is used for a toy model of molecular biology to assess conditions that lead to the edge of chaos (EOC) in a network of biomolecules. Results can enhance our ability to understand complex diseases and their treatment or cure.
biology
5,106
Discriminative Topological Features Reveal Biological Network Mechanisms
q-bio.MN
Recent genomic and bioinformatic advances have motivated the development of numerous random network models purporting to describe graphs of biological, technological, and sociological origin. The success of a model has been evaluated by how well it reproduces a few key features of the real-world data, such as degree di...
biology
5,107
Global Topological Study of the Protein-protein Interaction Networks
q-bio.MN
We employed the random graph theory approach to analyze the protein-protein interaction database DIP (Feb. 2004), for seven species (S. cerevisiae, H. pylori, E. coli, C. elegans, H. sapiens, M. musculus and D. melanogaster). Several global topological parameters (such as node connectivity, average diameter, node conne...
biology
5,108
Large-scale reverse engineering by the Lasso
q-bio.MN
We perform a reverse engineering from the ``extended Spellman data'', consisting of 6178 mRNA levels measured by microarrays at 73 instances in four time series during the cell cycle of the yeast Saccharomyces cerevisae. By assuming a linear model of the genetic regulatory network, and imposing an extra constraint (the...
biology
5,109
On the stability of Murray's testosterone model
q-bio.MN
We prove the global asymptotic stability of a well-known delayed negative-feedback model of testosterone dynamics, which has been proposed as a model of oscillatory behavior. We establish stability (and hence the impossibility of oscillations) even in the presence of delays of arbitrary length.
biology
5,110
Graphic requirements for multistationarity
q-bio.MN
We discuss properties which must be satisfied by a genetic network in order for it to allow differentiation. These conditions are expressed as follows in mathematical terms. Let $F$ be a differentiable mapping from a finite dimensional real vector space to itself. The signs of the entries of the Jacobian matrix of $F...
biology
5,111
Clustering under the line graph transformation: Application to reaction network
q-bio.MN
Many real networks can be understood as two complementary networks with two kind of nodes. This is the case of metabolic networks where the first network has chemical compounds as nodes and the second one has nodes as reactions. The second network can be related to the first one by a technique called line graph transfo...
biology
5,112
Green's Function Reaction Dynamics: a new approach to simulate biochemical networks at the particle level and in time and space
q-bio.MN
Biochemical networks are the analog computers of life. They allow living cells to control a large number of biological processes, such as gene expression and cell signalling. In biochemical networks, the concentrations of the components are often low. This means that the discrete nature of the reactants and the stochas...
biology
5,113
Bifurcation analysis of a model of the budding yeast cell cycle
q-bio.MN
We study the bifurcations of a set of nine nonlinear ordinary differential equations that describe the regulation of the cyclin-dependent kinase that triggers DNA synthesis and mitosis in the budding yeast, Saccharomyces cerevisiae. We show that Clb2-dependent kinase exhibits bistability (stable steady states of high o...
biology
5,114
Modeling Interactome: Scale-Free or Geometric?
q-bio.MN
Networks have been used to model many real-world phenomena to better understand the phenomena and to guide experiments in order to predict their behavior. Since incorrect models lead to incorrect predictions, it is vital to have a correct model. As a result, new techniques and models for analyzing and modeling real-wor...
biology
5,115
The Orchestral Analog of Molecular Biology
q-bio.MN
Signal processing (SP) techniques convert DNA and protein sequences into information that lead to successful drug discovery. One must, however, be aware about the difference between information and entropy1. Eight other physical properties of DNA and protein segments are suggested for SP analysis other than ones alread...
biology
5,116
Sampling rare switching events in biochemical networks
q-bio.MN
Bistable biochemical switches are ubiquitous in gene regulatory networks and signal transduction pathways. Their switching dynamics, however, are difficult to study directly in experiments or conventional computer simulations, because switching events are rapid, yet infrequent. We present a simulation technique that ma...
biology
5,117
The statistical mechanics of complex signaling networks : nerve growth factor signaling
q-bio.MN
It is becoming increasingly appreciated that the signal transduction systems used by eukaryotic cells to achieve a variety of essential responses represent highly complex networks rather than simple linear pathways. While significant effort is being made to experimentally measure the rate constants for individual steps...
biology
5,118
Cell Cycling Models of Carcinogenesis: A Complex Systems Analysis
q-bio.MN
A new approach to the modular, complex systems analysis of nonlinear dynamics in cell cycling network transformations involved in carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compar...
biology
5,119
Dynamics and coding of a biologically-motivated network
q-bio.MN
A four-node network consisting of a negative loop controlling a positive one is studied. It models some of the features of the p53 gene network. Using piecewise linear dynamics with thresholds, the allowed dynamical classes are fully characterized and coded. The biologically relevant situations are identified and concl...
biology
5,120
Quantifying the relevance of different mediators in the human immune cell network
q-bio.MN
Immune cells coordinate their efforts for the correct and efficient functioning of the immune system (IS). Each cell type plays a distinct role and communicates with other cell types through mediators such as cytokines, chemokines and hormones, among others, that are crucial for the functioning of the IS and its fine t...
biology
5,121
Chemical models of genetic toggle switches
q-bio.MN
We study by mean-field analysis and stochastic simulations chemical models for genetic toggle switches formed from pairs of genes that mutually repress each other. In order to determine the stability of the genetic switches, we make a connection with reactive flux theory and transition state theory. The switch stabilit...
biology
5,122
Scale-rich metabolic networks: background and introduction
q-bio.MN
Recent progress has clarified many features of the global architecture of biological metabolic networks, which have highly organized and optimized tolerances and tradeoffs (HOT) for functional requirements of flexibility, efficiency, robustness, and evolvability, with constraints on conservation of energy, redox, and m...
biology
5,123
High-dimensional switches and the modeling of cellular differentiation
q-bio.MN
Many genes have been identified as driving cellular differentiation, but because of their complex interactions, the understanding of their collective behaviour requires mathematical modelling. Intriguingly, it has been observed in numerous developmental contexts, and particularly hematopoiesis, that genes regulating di...
biology
5,124
Length, Protein-Protein Interactions, and Complexity
q-bio.MN
The evolutionary reason for the increase in gene length from archaea to prokaryotes to eukaryotes observed in large scale genome sequencing efforts has been unclear. We propose here that the increasing complexity of protein-protein interactions has driven the selection of longer proteins, as longer proteins are more ab...
biology
5,125
The efficiency of multi-target drugs: the network approach might help drug design
q-bio.MN
Despite considerable progress in genome- and proteome-based high-throughput screening methods and rational drug design, the number of successful single target drugs did not increase appreciably during the past decade. Network models suggest that partial inhibition of a surprisingly small number of targets can be more e...
biology
5,126
Chemical organization theory: towards a theory of constructive dynamical systems
q-bio.MN
Complex dynamical networks consisting of many components that interact and produce each other are difficult to understand, especially, when new components may appear. In this paper we outline a theory to deal with such systems. The theory consists of two parts. The first part introduces the concept of a chemical organi...
biology
5,127
Robustness and fragility of Boolean models for genetic regulatory networks
q-bio.MN
Interactions between genes and gene products give rise to complex circuits that enable cells to process information and respond to external signals. Theoretical studies often describe these interactions using continuous, stochastic, or logical approaches. We propose a new modeling framework for gene regulatory networks...
biology
5,128
Graph theoretic analysis of protein interaction networks of eukaryotes
q-bio.MN
Thanks to recent progress in high-throughput experimental techniques, the datasets of large-scale protein interactions of prototypical multicellular species, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, have been assayed. The datasets are obtained mainly by using the yeast hybrid ...
biology
5,129
The use of oscillatory signals in the study of genetic networks
q-bio.MN
The structure of a genetic network is uncovered by studying its response to external stimuli (input signals). We present a theory of propagation of an input signal through a linear stochastic genetic network. It is found that there are important advantages in using oscillatory signals over step or impulse signals, and ...
biology
5,130
Robustness in Gene Circuits: Clustering of Functional Responses
q-bio.MN
In contrast to engineering applications, in which the structure of control laws are designed to satisfy prescribed function requirements, in biology it is often necessary to infer gene-circuit function from incomplete data on gene-circuit structure. By using the feed-forward loop as a model system, this paper introduce...
biology
5,131
Probabilistic methods for predicting protein functions in protein-protein interaction networks
q-bio.MN
We discuss probabilistic methods for predicting protein functions from protein-protein interaction networks. Previous work based on Markov Randon Fields is extended and compared to a general machine-learning theoretic approach. Using actual protein interaction networks for yeast from the MIPS database and GO-SLIM funct...
biology
5,132
Computational Theory of Biological Function I
q-bio.MN
This series presents an approach to mathematical biology which makes precise the function of biological molecules. Because biological systems compute, the theory is a general purpose computer language. I build a language for efficiently representing the function of protein-like molecules in a cell. The first paper only...
biology
5,133
Application of Random Matrix Theory to Biological Networks
q-bio.MN
We show that spectral fluctuation of interaction matrices of yeast a core protein interaction network and a metabolic network follows the description of the Gaussian orthogonal ensemble (GOE) of random matrix theory (RMT). Furthermore, we demonstrate that while the global biological networks evaluated belong to GOE, re...
biology
5,134
Ubiquity of Log-normal Distributions in Intra-cellular Reaction Dynamic
q-bio.MN
The discovery of two fundamental laws concerning cellular dynamics with recursive growth is reported. First, the chemical abundances measured over many cells are found to obey a log-normal distribution and second, the relationship between the average and standard deviation of the abundances is found to be linear. The u...
biology
5,135
Geometrical constraints in a gene network model and pattern formation
q-bio.MN
A fundamental task in developmental biology is to identify the mechanisms which drive morphogenesis. In many cases, pattern formation is driven by the positional information determined by both the gradient of maternal factors and hard-wired mechanisms embedded in the genome. Alternative mechanisms of positional informa...
biology
5,136
Self-organization of gene regulatory network motifs enriched with short transcript's half-life transcription factors
q-bio.MN
Network motifs, the recurring regulatory structural patterns in networks, are able to self-organize to produce networks. Three major motifs, feedforward loop, single input modules and bi-fan are found in gene regulatory networks. The large ratio of genes to transcription factors (TFs) in genomes leads to a sharing of T...
biology
5,137
Low Degree Metabolites Explain Essential Reactions and Enhance Modularity in Biological Networks
q-bio.MN
Recently there has been a lot of interest in identifying modules at the level of genetic and metabolic networks of organisms, as well as in identifying single genes and reactions that are essential for the organism. A goal of computational and systems biology is to go beyond identification towards an explanation of spe...
biology
5,138
Virtual Identification of Essential Proteins Within the Protein Interaction Network of Yeast
q-bio.MN
Topological analysis of large scale protein-protein interaction networks (PINs) is important for understanding the organisational and functional principles of individual proteins. The number of interactions that a protein has in a PIN has been observed to be correlated with its indispensability. Essential proteins gene...
biology
5,139
Some protein interaction data do not exhibit power law statistics
q-bio.MN
It has been claimed that protein-protein interaction (PPI) networks are scale-free based on the observation that the node degree sequence follows a power law. Here we argue that these claims are likely to be based on erroneous statistical analysis. Typically, the supporting data are presented using frequency-degree plo...
biology
5,140
Probability Models for Degree Distributions of Protein Interaction Networks
q-bio.MN
The degree distribution of many biological and technological networks has been described as a power-law distribution. While the degree distribution does not capture all aspects of a network, it has often been suggested that its functional form contains important clues as to underlying evolutionary processes that have s...
biology
5,141
Signal detection, modularity and the correlation between extrinsic and intrinsic noise in biochemical networks
q-bio.MN
Understanding cell function requires an accurate description of how noise is transmitted through biochemical networks. We present an analytical result for the power spectrum of the output signal of a biochemical network that takes into account the correlations between the noise in the input signal (the extrinsic noise)...
biology
5,142
Identification of the growth-limiting step in continuous cultures from initial rates measured in response to substrate-excess conditions
q-bio.MN
When steady state chemostat cultures are abruptly exposed to substrate-excess conditions, they exhibit long lags before adjusting to the new environment. The identity of the rate-limiting step for this slow response can be inferred from the initial yields and specific growth rates measured by exposing steady state cult...
biology
5,143
Algorithmic and Complexity Results for Decompositions of Biological Networks into Monotone Subsystems
q-bio.MN
A useful approach to the mathematical analysis of large-scale biological networks is based upon their decompositions into monotone dynamical systems. This paper deals with two computational problems associated to finding decompositions which are optimal in an appropriate sense. In graph-theoretic language, the problems...
biology
5,144
Comparative analysis of some models of mixed-substrate microbial growth
q-bio.MN
Mixed-substrate microbial growth is among the most intensely studied systems in molecular microbiology. Several mathematical models have been developed to account for the genetic regulation of such systems, especially those resulting in diauxic growth. In this work, we compare the dynamics of three such models (Narang,...
biology
5,145
A p53 Oscillator Model of DNA Break Repair Control
q-bio.MN
The transcription factor p53 is an important regulator of cell fate. Mutations in p53 gene are associated with many cancers. In response to signals such as DNA damage, p53 controls the transcription of a series of genes that cause cell cycle arrest during which DNA damage is repaired, or triggers programmed cell death ...
biology
5,146
Network growth models and genetic regulatory networks
q-bio.MN
We study a class of growth algorithms for directed graphs that are candidate models for the evolution of genetic regulatory networks. The algorithms involve partial duplication of nodes and their links, together with innovation of new links, allowing for the possibility that input and output links from a newly created ...
biology
5,147
Content based network model with duplication and divergence
q-bio.MN
We construct a minimal content-based realization of the duplication and divergence model of genomic networks introduced by Wagner [A. Wagner, Proc. Natl. Acad. Sci. {\bf 91}, 4387 (1994)] and investigate the scaling properties of the directed degree distribution and clustering coefficient. We find that the content base...
biology
5,148
Mathematical approaches to differentiation and gene regulation
q-bio.MN
We consider some mathematical issues raised by the modelling of gene networks. The expression of genes is governed by a complex set of regulations, which is often described symbolically by interaction graphs. Once such a graph has been established, there remains the difficult task to decide which dynamical properties o...
biology
5,149
Scale- free networks in cell biology
q-bio.MN
A cell's behavior is a consequence of the complex interactions between its numerous constituents, such as DNA, RNA, proteins and small molecules. Cells use signaling pathways and regulatory mechanisms to coordinate multiple processes, allowing them to respond to and adapt to an ever-changing environment. The large numb...
biology
5,150
Absolute Rate Theories of Epigenetic Stability
q-bio.MN
Spontaneous switching events in most characterized genetic switches are rare, resulting in extremely stable epigenetic properties. We show how simple arguments lead to theories of the rate of such events much like the absolute rate theory of chemical reactions corrected by a transmission factor. Both the probability of...
biology
5,151
Uniqueness of steady states for a certain chemical reaction
q-bio.MN
Samoilov, Plyasunov, and Arkin provide an example of a chemical reaction whose full stochastic (Master Equation) model exhibits bistable behavior, but for which the deterministic (mean field) version has a unique steady state at least for special parameter values. In this short note, we provide a proof of uniqueness va...
biology
5,152
A dichotomy for a class of cyclic delay systems
q-bio.MN
Two complementary analyses of a cyclic negative feedback system with delay are considered in this paper. The first analysis applies the work by Sontag, Angeli, Enciso and others regarding monotone control systems under negative feedback, and it implies the global attractiveness towards an equilibrium for arbitrary dela...
biology
5,153
Complex networks theory for analyzing metabolic networks
q-bio.MN
One of the main tasks of post-genomic informatics is to systematically investigate all molecules and their interactions within a living cell so as to understand how these molecules and the interactions between them relate to the function of the organism, while networks are appropriate abstract description of all kinds ...
biology
5,154
Diffusion and interfaces in pattern formation
q-bio.MN
We discuss several qualitative properties of the solutions of reaction-diffusion systems and equations of the form $u_t = \epsilon^2 D \Delta u + f(u,x,\epsilon t)$, that are used in modeling pattern formation. We analyze the diffusion neutral and the diffusion dependent situations that, in the time autonomous case, ar...
biology
5,155
Genetic Toggle Switch Without Cooperative Binding
q-bio.MN
Genetic switch systems with mutual repression of two transcription factors are studied using deterministic and stochastic methods. Numerous studies have concluded that cooperative binding is a necessary condition for the emergence of bistability in these systems. Here we show that for a range of biologically relevant c...
biology
5,156
Diffusion of transcription factors can drastically enhance the noise in gene expression
q-bio.MN
We study by simulation the effect of the diffusive motion of repressor molecules on the noise in mRNA and protein levels in the case of a repressed gene. We find that spatial fluctuations due to diffusion can drastically enhance the noise in gene expression. For a fixed repressor strength, the noise due to diffusion ca...
biology
5,157
Complex Qualitative Models in Biology: a new approach
q-bio.MN
We advocate the use of qualitative models in the analysis of large biological systems. We show how qualitative models are linked to theoretical differential models and practical graphical models of biological networks. A new technique for analyzing qualitative models is introduced, which is based on an efficient repres...
biology
5,158
Hierarchical modularity of nested bow-ties in metabolic networks
q-bio.MN
The exploration of the structural topology and the organizing principles of genome-based large-scale metabolic networks is essential for studying possible relations between structure and functionality of metabolic networks. Topological analysis of graph models has often been applied to study the structural characterist...
biology
5,159
Superstability of the yeast cell cycle dynamics: Ensuring causality in the presence of biochemical stochasticity
q-bio.MN
Gene regulatory dynamics is governed by molecular processes and therefore exhibits an inherent stochasticity. However, for the survival of an organism it is a strict necessity that this intrinsic noise does not prevent robust functioning of the system. It is still an open question how dynamical stability is achieved in...
biology
5,160
Stochastic Model of Yeast Cell Cycle Network
q-bio.MN
Biological functions in living cells are controlled by protein interaction and genetic networks. These molecular networks should be dynamically stable against various fluctuations which are inevitable in the living world. In this paper, we propose and study a stochastic model for the network regulating the cell cycle o...
biology
5,161
Aging cellular networks: chaperones as major participants
q-bio.MN
We increasingly rely on the network approach to understand the complexity of cellular functions. Chaperones (heat shock proteins) are key "networkers", which have among their functions to sequester and repair damaged protein. In order to link the network approach and chaperones with the aging process, we first summariz...
biology
5,162
Impact of observational incompleteness on the structural properties of protein interaction networks
q-bio.MN
The observed structure of protein interaction networks is corrupted by many false positive/negative links. This observational incompleteness is abstracted as random link removal and a specific, experimentally motivated (spoke) link rearrangement. Their impact on the structural properties of gene-duplication-and-mutatio...
biology
5,163
Spontaneous Self-Assembly of Transcription Factor Based Gene Regulation Networks
q-bio.MN
We model the transcription factor based regulation network of yeast using a content-based network model that mimicks the recognition of binding motifs on the regulatory regions of the genes. We are thereby able to faithfully reproduce many of the topological features of the gene regulatory network of yeast once the par...
biology
5,164
Evolution of Protein Interaction Networks by Whole Genome Duplication and Domain Shuffling
q-bio.MN
Successive whole genome duplications have recently been firmly established in all major eukaryote kingdoms. It is not clear, however, how such dramatic evolutionary process has contributed to shape the large scale topology of protein-protein interaction (PPI) networks. We propose and analytically solve a generic model ...
biology
5,165
Dynamic re-wiring of protein interaction: The case of transactivation
q-bio.MN
We are looking at local protein interaction networks from the perspective of directed, labeled graphs with quantitative values for monotonic changes in concentrations. These systems can be used to perform stability analysis for a stable attractor, given initial values. They can also show re-configuration of whole syste...
biology
5,166
Dynamic Studies of Scaffold-dependent Mating Pathway in Yeast
q-bio.MN
The mating pathway in \emph{Saccharomyces cerevisiae} is one of the best understood signal transduction pathways in eukaryotes. It transmits the mating signal from plasma membrane into the nucleus through the G-protein coupled receptor and the mitogen-activated protein kinase (MAPK) cascade. According to the current un...
biology
5,167
Comparative study of the transcriptional regulatory networks of E. coli and yeast: Structural characteristics leading to marginal dynamic stability
q-bio.MN
Dynamical properties of the transcriptional regulatory network of {\it Escherichia coli} and {\it Saccharomyces cerevisiae} are studied within the framework of random Boolean functions. The dynamical response of these networks to a single point mutation is characterized by the number of mutated elements as a function o...
biology
5,168
Genetic Regulation of Fluxes: Iron Homeostasis of Escherichia coli
q-bio.MN
Iron is an essential trace-element for most organisms. However, because high concentration of free intracellular iron is cytotoxic, cells have developed complex regulatory networks that keep free intracellular iron concentration at optimal range, allowing the incorporation of the metal into iron-using enzymes and minim...
biology
5,169
Function Constrains Network Architecture and Dynamics: A Case Study on the Yeast Cell Cycle Boolean Network
q-bio.MN
We develop a general method to explore how the function performed by a biological network can constrain both its structural and dynamical network properties. This approach is orthogonal to prior studies which examine the functional consequences of a given structural feature, for example a scale free architecture. A key...
biology
5,170
Robustness and modular design of the Drosophila segment polarity network
q-bio.MN
Biomolecular networks have to perform their functions robustly. A robust function may have preferences in the topological structures of the underlying network. We carried out an exhaustive computational analysis on network topologies in relation to a patterning function in Drosophila embryogenesis. We found that while ...
biology
5,171
Bow-tie topological features of metabolic networks and the functional significance
q-bio.MN
Exploring the structural topology of genome-based large-scale metabolic network is essential for investigating possible relations between structure and functionality. Visualization would be helpful for obtaining immediate information about structural organization. In this work, metabolic networks of 75 organisms were i...
biology
5,172
Oscillation patterns in negative feedback loops
q-bio.MN
Organisms are equipped with regulatory systems that display a variety of dynamical behaviours ranging from simple stable steady states, to switching and multistability, to oscillations. Earlier work has shown that oscillations in protein concentrations or gene expression levels are related to the presence of at least o...
biology
5,173
Efficient Degradation and Expression Prioritization with Small RNAs
q-bio.MN
We build a simple model for feedback systems involving small RNA (sRNA) molecules based on the iron metabolism system in the bacterium E. coli, and compare it with the corresponding system in H. pylori which uses purely transcriptional regulation. This reveals several unique features of sRNA based regulation that could...
biology
5,174
Monotone and near-monotone network structure (part I)
q-bio.MN
This paper (parts I and II) provides an expository introduction to monotone and near-monotone dynamical systems associated to biochemical networks, those whose graphs are consistent or near-consistent. Many conclusions can be drawn from signed network structure, associated to purely stoichiometric information and ignor...
biology
5,175
Directionality is an inherent property of biochemical networks
q-bio.MN
Thermodynamic constraints on reactions directions are inherent in the structure of a given biochemical network. However, concrete procedures for determining feasible reaction directions for large-scale metabolic networks are not well established. This work introduces a systematic approach to compute reaction directions...
biology
5,176
Designing sequential transcription logic: a simple genetic circuit for conditional memory
q-bio.MN
The ability to learn and respond to recurrent events depends on the capacity to remember transient biological signals received in the past. Moreover, it may be desirable to remember or ignore these transient signals conditioned upon other signals that are active at specific points in time or in unique environments. Her...
biology
5,177
Dynamical robustness of biological networks with hierarchical distribution of time scales
q-bio.MN
We propose the concepts of distributed robustness and r-robustness, well adapted to functional genetics. Then we discuss the robustness of the relaxation time using a chemical reaction description of genetic and signalling networks. First, we obtain the following result for linear networks: for large multiscale systems...
biology
5,178
Molecular chaperones: The modular evolution of cellular networks
q-bio.MN
Molecular chaperones play a prominent role in signaling and transcriptional regulatory networks of the cell. Recent advances uncovered that chaperones act as genetic buffers stabilizing the phenotype of various cells and organisms and may serve as potential regulators of evolvability. Chaperones have weak links, connec...
biology
5,179
Attractors in continuous and Boolean networks
q-bio.MN
We study the stable attractors of a class of continuous dynamical systems that may be idealized as networks of Boolean elements, with the goal of determining which Boolean attractors, if any, are good approximations of the attractors of generic continuous systems. We investigate the dynamics in simple rings and rings w...
biology
5,180
Comparing Protein Interaction Networks via a Graph Match-and-Split Algorithm
q-bio.MN
We present a method that compares the protein interaction networks of two species to detect functionally similar (conserved) protein modules between them. The method is based on an algorithm we developed to identify matching subgraphs between two graphs. Unlike previous network comparison methods, our algorithm has pro...
biology
5,181
Stochastic Simulations of Genetic Switch Systems
q-bio.MN
Genetic switch systems with mutual repression of two transcription factors are studied using deterministic methods (rate equations) and stochastic methods (the master equation and Monte Carlo simulations). These systems exhibit bistability, namely two stable states such that spontaneous transitions between them are rar...
biology
5,182
Stress-induced rearrangements of cellular networks: consequences for protection and drug design
q-bio.MN
The complexity of the cells can be described and understood by a number of networks such as protein-protein interaction, cytoskeletal, organelle, signalling, gene transcription and metabolic networks. All these networks are highly dynamic producing continuous rearrangements in their links, hubs, network-skeleton and mo...
biology
5,183
Bistability preserving model reduction in apoptosis
q-bio.MN
Biological systems are typically very complex and need to be reduced before they are amenable to a thorough analysis. Also, they often possess functionally important dynamic features like bistability. In model reduction, it is sometimes more desirable to preserve the dynamic features only than to recover a good quantit...
biology
5,184
Compositionality, stochasticity and cooperativity in dynamic models of gene regulation
q-bio.MN
We present an approach for constructing dynamic models for the simulation of gene regulatory networks from simple computational elements. Each element is called a ``gene gate'' and defines an input/output-relationship corresponding to the binding and production of transcription factors. The proposed reaction kinetics o...
biology
5,185
microRNAs may sharpen spatial expression patterns
q-bio.MN
The precise layout of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low expression domains requires a genetic mechanism which is both sensitive and robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently it has been demon...
biology
5,186
On the equilibria of the MAPK cascade: cooperativity, modularity and bistability
q-bio.MN
In this paper we present a discussion of a phenomenological model of the MAPK cascade which was originally proposed by Angeli et al. (PNAS 101, 1822 (2004)). The model and its solution are extended in several respects: a) an analytical solution is given for the cascade equilibria, exploiting a parameter-based symmetry ...
biology
5,187
Representing perturbed dynamics in biological network models
q-bio.MN
We study the dynamics of gene activities in relatively small size biological networks (up to a few tens of nodes), e.g. the activities of cell-cycle proteins during the mitotic cell-cycle progression. Using the framework of deterministic discrete dynamical models, we characterize the dynamical modifications in response...
biology
5,188
Oscillations and temporal signalling in cells
q-bio.MN
The development of new techniques to quantitatively measure gene expression in cells has shed light on a number of systems that display oscillations in protein concentration. Here we review the different mechanisms which can produce oscillations in gene expression or protein concentration, using a framework of simple m...
biology
5,189
Quantitative Characterization of Combinatorial Transcriptional Control of the Lactose Operon of E. coli
q-bio.MN
It is the goal of systems biology to understand the behavior of the whole in terms of the knowledge of the parts. This is hard to achieve in many cases due to the difficulty of characterizing the many constituents and their complex web of interactions involved in a biological system. The lac promoter of E. coli offers ...
biology
5,190
The regulatory network of E. coli metabolism as a boolean dynamical system exhibits both homeostasis and flexibility of response
q-bio.MN
Elucidating the architecture and dynamics of large scale genetic regulatory networks of cells is an important goal in systems biology. We study the system level dynamical properties of the genetic network of Escherichia coli that regulates its metabolism, and show how its design leads to biologically useful cellular pr...
biology
5,191
Boolean network model predicts cell cycle sequence of fission yeast
q-bio.MN
A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle ...
biology
5,192
A generic mechanism for adaptive growth rate regulation
q-bio.MN
How can a microorganism adapt to a variety of environmental conditions despite there exists a limited number of signal transduction machineries? We show that for any growing cells whose gene expression is under stochastic fluctuations, adaptive cellular state is inevitably selected by noise, even without specific signa...
biology
5,193
Information flow and optimization in transcriptional control
q-bio.MN
In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be possible to transmit much more than just one regulatory bit. Realizing this opt...
biology
5,194
Viable flux distribution in metabolic networks
q-bio.MN
The metabolic networks are very well characterized for a large set of organisms, a unique case in within the large-scale biological networks. For this reason they provide a a very interesting framework for the construction of analytically tractable statistical mechanics models. In this paper we introduce a solvable m...
biology
5,195
Comment on "Regularizing capacity of metabolic networks"
q-bio.MN
In a recent paper, Marr, Muller-Linow and Hutt [Phys. Rev. E 75, 041917 (2007)] investigate an artificial dynamic system on metabolic networks. They find a less complex time evolution of this dynamic system in real networks, compared to networks of reference models. The authors argue that this suggests that metabolic n...
biology
5,196
Comparing Classical Pathways and Modern Networks: Towards the Development of an Edge Ontology
q-bio.MN
Pathways are integral to systems biology. Their classical representation has proven useful but is inconsistent in the meaning assigned to each arrow (or edge) and inadvertently implies the isolation of one pathway from another. Conversely, modern high-throughput experiments give rise to standardized networks facilitati...
biology
5,197
Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism
q-bio.MN
We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For this, we generate synthetic metabolic profiles for benchmarking purposes based on a well-established model for red blood...
biology
5,198
Multi-bit information storage by multisite phosphorylation
q-bio.MN
Cells store information in DNA and in stable programs of gene expression, which thereby implement forms of long-term cellular memory. Cells must also possess short-term forms of information storage, implemented post-translationally, to transduce and interpret external signals. CaMKII, for instance, is thought to implem...
biology
5,199
Reliability of genetic networks is evolvable
q-bio.MN
Control of the living cell functions with remarkable reliability despite the stochastic nature of the underlying molecular networks -- a property presumably optimized by biological evolution. We here ask to what extent the property of a stochastic dynamical network to produce reliable dynamics is an evolvable trait. Us...
biology