Search results for "Quantitative Biology - Molecular Networks"
showing 9 items of 9 documents
Multiple steady states and the form of response functions to antigen in a model for the initiation of T cell activation
2017
The aim of this paper is to study the qualitative behaviour predicted by a mathematical model for the initial stage of T-cell activation. The state variables in the model are the concentrations of phosphorylation states of the T-cell receptor (TCR) complex and the phosphatase SHP-1 in the cell. It is shown that these quantities cannot approach zero and that the model possesses more than one positive steady state for certain values of the parameters. It can also exhibit damped oscillations. It is proved that the chemical concentration which represents the degree of activation of the cell, that of the maximally phosphorylated form of the TCR complex, is, in general, a non-monotone function of…
Gene-based and semantic structure of the Gene Ontology as a complex network
2012
The last decade has seen the advent and consolidation of ontology based tools for the identification and biological interpretation of classes of genes, such as the Gene Ontology. The information accumulated time-by-time and included in the GO is encoded in the definition of terms and in the setting up of semantic relations amongst terms. This approach might be usefully complemented by a bottom-up approach based on the knowledge of relationships amongst genes. To this end, we investigate the Gene Ontology from a complex network perspective. We consider the semantic network of terms naturally associated with the semantic relationships provided by the Gene Ontology consortium and a gene-based …
Sustained oscillations in the MAP kinase cascade.
2016
Abstract The MAP kinase cascade is a network of enzymatic reactions arranged in layers. In each layer occurs a multiple futile cycle of phosphorylations. The fully phosphorylated substrate then serves as an enzyme for the layer below. This paper focuses on the existence of parameters for which Hopf bifurcations occur and generate periodic orbits. Furthermore it is explained how geometric singular perturbation theory allows to generalize results from simple models to more complex ones.
Identification of control targets in Boolean molecular network models via computational algebra
2015
Motivation: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The pot…
Organization and evolution of synthetic idiotypic networks
2012
We introduce a class of weighted graphs whose properties are meant to mimic the topological features of idiotypic networks, namely the interaction networks involving the B-core of the immune system. Each node is endowed with a bit-string representing the idiotypic specificity of the corresponding B cell and a proper distance between any couple of bit-strings provides the coupling strength between the two nodes. We show that a biased distribution of the entries in bit-strings can yield fringes in the (weighted) degree distribution, small-worlds features, and scaling laws, in agreement with experimental findings. We also investigate the role of ageing, thought of as a progressive increase in …
Overload breakdown in models for photosynthesis
2015
In many models of the Calvin cycle of photosynthesis it is observed that there are solutions where concentrations of key substances belonging to the cycle tend to zero at late times, a phenomenon known as overload breakdown. In this paper we prove theorems about the existence and non-existence of solutions of this type and obtain information on which concentrations tend to zero when overload breakdown occurs. As a starting point we take a model of Pettersson and Ryde-Pettersson which seems to be prone to overload breakdown and a modification of it due to Poolman which was intended to avoid this effect.
The minimal model of Hahn for the Calvin cycle.
2018
There are many models of the Calvin cycle of photosynthesis in the literature. When investigating the dynamics of these models one strategy is to look at the simplest possible models in order to get the most detailed insights. We investigate a minimal model of the Calvin cycle introduced by Hahn while he was pursuing this strategy. In a variant of the model not including photorespiration it is shown that there exists exactly one positive steady state and that this steady state is unstable. For generic initial data either all concentrations tend to infinity at lates times or all concentrations tend to zero at late times. In a variant including photorespiration it is shown that for suitable v…
A proof of bistability for the dual futile cycle
2014
Abstract The multiple futile cycle is an important building block in networks of chemical reactions arising in molecular biology. A typical process which it describes is the addition of n phosphate groups to a protein. It can be modelled by a system of ordinary differential equations depending on parameters. The special case n = 2 is called the dual futile cycle. The main result of this paper is a proof that there are parameter values for which the system of ODE describing the dual futile cycle has two distinct stable stationary solutions. The proof is based on bifurcation theory and geometric singular perturbation theory. An important entity built of three coupled multiple futile cycles is…
Structure Learning in Nested Effects Models
2007
Nested Effects Models (NEMs) are a class of graphical models introduced to analyze the results of gene perturbation screens. NEMs explore noisy subset relations between the high-dimensional outputs of phenotyping studies, e.g., the effects showing in gene expression profiles or as morphological features of the perturbed cell. In this paper we expand the statistical basis of NEMs in four directions. First, we derive a new formula for the likelihood function of a NEM, which generalizes previous results for binary data. Second, we prove model identifiability under mild assumptions. Third, we show that the new formulation of the likelihood allows efficiency in traversing model space. Fourth, we…