分子网络
The effects of intrinsic noise on stochastic delay systems is studied within an expansion in the inverse system size. We show that the stochastic nature of the underlying dynamics may induce oscillatory behaviour in parameter ranges where…
Biochemical networks can respond to temporal characteristics of time-varying signals. To understand how reliably biochemical networks can transmit information we must consider how an input signal as a function of time--the input…
We show how to construct a reduced description of interacting genes in noisy, small regulatory networks using coupled binary "spin" variables. Treating both the protein number and gene expression state variables stochastically and on equal…
Noise in the expression of a gene produces fluctuations in the concentration of the gene product. These fluctuations can interfere with optimal function or can be exploited to generate beneficial diversity between cells; gene expression…
A metabolic model can be represented as bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a…
In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its…
Phenotypic heterogeneity in an isogenic, microbial population enables a subset of the population to persist under stress. In mycobacteria, stresses like nutrient and oxygen deprivation activate the stress response pathway involving the…
A ubiquitous building block of signaling pathways is a cycle of covalent modification (e.g., phosphorylation and dephosphorylation in MAPK cascades). Our paper explores the kind of information processing and filtering that can be…
Experiments in recent years have vividly demonstrated that gene expression can be highly stochastic. How protein concentration fluctuations affect the growth rate of a population of cells, is, however, a wide open question. We present a…
Chemical reaction systems with a low to moderate number of molecules are typically modeled as discrete jump Markov processes. These systems are oftentimes simulated with methods that produce statistically exact sample paths such as the…
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,…
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…
Autophagy is a conserved biological stress response in mammalian cells that is responsible for clearing damaged proteins and organelles from the cytoplasm and recycling their contents via the lysosomal pathway. In cases of mild stress,…
With the advent of high-throughput wet lab technologies the amount of protein interaction data available publicly has increased substantially, in turn spurring a plethora of computational methods for in silico knowledge discovery from this…
Gene duplication is believed to play a major role in the evolution of genomic complexity. The presence of a duplicate removes the constraint of natural selection upon the gene, leading to its likely loss of function or, occasionally, the…
Many events in the vertebrate immune system are influenced by some element of chance. The objective of the present work is to describe affinity maturation of B lymphocytes (in which random events are perhaps the most characteristic), and to…
One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed…
Genetically identical cells in the same population can take on phenotypically variable states, leading to differentiated responses to external signals, such as nutrients and drug-induced stress. Many models and experiments have focused on a…
How do mammalian cells that share the same genome exist in notably distinct phenotypes, exhibiting differences in morphology, gene expression patterns, and epigenetic chromatin statuses? Furthermore how do cells of different phenotypes…
Genetic interaction can be defined as a deviation of the phenotypic quantitative effect of a double gene mutation from the effect predicted from single mutations using a simple (e.g., multiplicative or linear additive) statistical model.…