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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 |
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