分子网络
We present an analytical treatment of a genetic switch model consisting of two mutually inhibiting genes operating without cooperative binding of the corresponding transcription factors. Previous studies have numerically shown that these…
Molecular noise in gene regulatory networks has two intrinsic components, one part being due to fluctuations caused by the birth and death of protein or mRNA molecules which are often present in small numbers and the other part arising from…
Gene expression levels exhibit stochastic variations among genetically identical organisms under the same environmental conditions (called gene expression "noise" or phenotype "fluctuation"). In yeast and Escherichia coli, positive…
Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical…
We study the effect of intrinsic noise on the thermodynamic balance of complex chemical networks subtending cellular metabolism and gene regulation. A topological network property called deficiency, known to determine the possibility of…
We compare the informational architecture of biological and random networks to identify informational features that may distinguish biological networks from random. The study presented here focuses on the Boolean network model for…
Successful adaptation helped the emergence of complexity. Alternating plastic- and rigid-like states were recurrently considered to play a role in adaptive processes. However, this extensive knowledge remained fragmented. In this paper I…
Mathematical models are increasingly being used to understand complex biochemical systems, to analyze experimental data and make predictions about unobserved quantities. However, we rarely know how robust our conclusions are with respect to…
In this review we discuss different mathematical models of gene regulatory networks as relevant to the onset and development of cancer. After discussion of alternative modelling approaches, we use a paradigmatic two-gene network to focus on…
Despite recent technological advances in genomic sciences, our understanding of cancer progression and its driving genetic alterations remains incomplete. Here, we introduce TiMEx, a generative probabilistic model for detecting patterns of…
Multiple phenotypic states often arise in a single cell with different gene-expression states that undergo transcription regulation with positive feedback. Recent experiments have shown that at least in E. coli, the gene state switching can…
Model reduction of biochemical networks relies on the knowledge of slow and fast variables. We provide a geometric method, based on the Newton polytope, to identify slow variables of a biochemical network with polynomial rate functions. The…
Gene regulatory network (GRN) modeling is a well-established theoretical framework for the study of cell-fate specification during developmental processes. Recently, dynamical models of GRNs have been taken as a basis for formalizing the…
We developed a strategy to control p53 levels when the p53 concentration falls below a desired threshold . Based on an established p53-MDM2 mathematical model that also incorporates microRNA regulators (p53-MDM2-miRNA), we applied a control…
Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age, and do not have measurable reductions in reproductive capacity…
We show how one may analytically compute the stationary density of the distribution of molecular constituents in populations of cells in the presence of noise arising from either bursting transcription or translation, or noise in…
Noise caused by fluctuations at the molecular level is a fundamental part of intracellular processes. While the response of biological systems to noise has been studied extensively, there has been limited understanding of how to exploit it…
SMAR1 is a sensitive signaling molecule in p53 regulatory network which can drive p53 network dynamics to three distinct states, namely, stabilized (two), damped and sustain oscillation states. In the interaction of p53 network with SMAR1,…
Background: Synthetic lethality (SL) refers to the genetic interaction between two or more genes where only their co-alteration (e.g. by mutations, amplifications or deletions) results in cell death. In recent years, SL has emerged as an…
Inside individual cells, expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers. Since proteins half-lives can be comparable to the cell-cycle length, randomness in…