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Gene expression profiles and protein dynamics in single cells have a large cell-to-cell variability due to intracellular noise. Intracellular fluctuations originate from two sources: intrinsic noise due to the pr...
In genomics, highly relevant gene interaction (co-expression) networks have been constructed by finding significant pair-wise correlations between genes in expression datasets. These networks are then mined to...
The cyclic AMP-Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved signal transduction mechanism that regulates cellular growth and differentiation in animals and fungi. We present a mathematica...
In Saccharomyces cerevisiæ, structural bistability generates a bimodal expression of the galactose uptake genes (GAL) when exposed to low and high glucose concentrations. This indicates that yeast cells can decid...
Hematopoietic ontogeny is characterized by overlapping waves of primitive, fetal definitive, and adult definitive erythroid lineages. Our aim is to identify differences in the transcriptional control of these ...
Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightl...
The genome-scale metabolic model of Saccharomyces cerevisiae , first presented in 2003, was the first genome-scale network reconstruction for a eukaryotic organism. Since then continuous efforts have been made in...
Genome-scale metabolic models are important tools in systems biology. They permit the in-silico prediction of cellular phenotypes via mathematical optimisation procedures, most importantly flux balance analysis. ...
Essential hypertension (EH) is a complex disease as a consequence of interaction between environmental factors and genetic background, but the pathogenesis of EH remains elusive. The emerging tools of network ...
24-hour biological clocks are intimately connected to the cellular signalling network, which complicates the analysis of clock mechanisms. The transcriptional regulator TOC1 (TIMING OF CAB EXPRESSION 1) is a f...
Recent studies have demonstrated that the activation of NADPH oxidase 1 (Nox1) plays an important role in the control of reactive oxygen species and their involvement in vascular physiology and pathophysiology...
The unfolded protein response (UPR) is a major signalling cascade acting in the quality control of protein folding in the endoplasmic reticulum (ER). The cascade is known to play an accessory role in a range o...
A wide range of bacteria species are known to communicate through the so called quorum sensing (QS) mechanism by means of which they produce a small molecule that can freely diffuse in the environment and in t...
The topological features of disease genes within interaction networks are the subject of intense study, as they shed light on common mechanisms of pathology and are useful for uncovering additional disease gen...
The stressosome is a bacterial signalling complex that responds to environmental changes by initiating a protein partner switching cascade, which leads to the release of the alternative sigma factor, σB. Stress p...
Focal adhesions are integrin-based cell-matrix contacts that transduce and integrate mechanical and biochemical cues from the environment. They develop from smaller and more numerous focal complexes under the ...
Graph-based modularity analysis has emerged as an important tool to study the functional organization of biological networks. However, few methods are available to study state-dependent changes in network modu...
Signal transduction plays a fundamental role in the understanding of cellular physiology. The bacterial phosphotransferase system (PTS) together with the PEP/pyruvate node in central metabolism represents a si...
Network inference is an important tool to reveal the underlying interactions of biological systems. In the liver, a complex system of transcription factors is active to distribute signals and induce the cellul...
Collective rhythms of gene regulatory networks have been a subject of considerable interest for biologists and theoreticians, in particular the synchronization of dynamic cells mediated by intercellular commun...
Cell cycle process of budding yeast (Saccharomyces cerevisiae) consists of four phases: G1, S, G2 and M. Initiated by stimulation of the G1 phase, cell cycle returns to the G1 stationary phase through a sequence ...
Apoptosis is an essential property of all higher organisms that involves extremely complex signaling pathways. Mathematical modeling provides a rigorous integrative approach for analyzing and understanding suc...
Site-specific Transcription Factors (TFs) are proteins that bind to specific sites on the DNA and control the activity of a target gene by enhancing or decreasing the rate at which the gene is transcribed by R...
Predicting a system’s behavior based on a mathematical model is a primary task in Systems Biology. If the model parameters are estimated from experimental data, the parameter uncertainty has to be translated i...
Various computational models have been of interest due to their use in the modelling of gene regulatory networks (GRNs). As a logical model, probabilistic Boolean networks (PBNs) consider molecular and genetic...
The topological analysis of biological networks has been a prolific topic in network science during the last decade. A persistent problem with this approach is the inherent uncertainty and noisy nature of the ...
The skeleton of complex systems can be represented as networks where vertices represent entities, and edges represent the relations between these entities. Often it is impossible, or expensive, to determine th...
Stochastic fluctuations in molecular numbers have been in many cases shown to be crucial for the understanding of biochemical systems. However, the systematic study of these fluctuations is severely hindered b...
In this paper, we present a framework for improving the accuracy of fixed-step methods for Monte Carlo simulation of discrete stochastic chemical kinetics. Stochasticity is ubiquitous in many areas of cell bio...
The three layer mitogen activated protein kinase (MAPK) signaling cascade exhibits different designs of interactions between its kinases and phosphatases. While the sequential interactions between the three ki...
Stochastic biochemical reaction networks are commonly modelled by the chemical master equation, and can be simulated as first order linear differential equations through a finite state projection. Due to the v...
Constraint-based analysis of genome-scale metabolic models typically relies upon maximisation of a cellular objective function such as the rate or efficiency of biomass production. Whilst this assumption may b...
It is well known that the deterministic dynamics of biochemical reaction networks can be more easily studied if timescale separation conditions are invoked (the quasi-steady-state assumption). In this case the...
Network motifs provided a “conceptual tool” for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, ...
Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells. In multicellular organisms, transcription factors and microRNAs are the major families of gene re...
Given the complex mechanisms underlying biochemical processes systems biology researchers tend to build ever increasing computational models. However, dealing with complex systems entails a variety of problems...
Transcription networks define the core of the regulatory machinery of cellular life and are largely responsible for information processing and decision making. At the small scale, interaction motifs have been ...
Drug resistance has now posed more severe and emergent threats to human health and infectious disease treatment. However, wet-lab approaches alone to counter drug resistance have so far still achieved limited ...
Constructing predictive dynamic models of interacting signalling networks remains one of the great challenges facing systems biology. While detailed dynamical data exists about individual pathways, the task of...
In Escherichia coli, overlapping rounds of DNA replication allow the bacteria to double in faster times than the time required to copy the genome. The precise timing of initiation of DNA replication is determined...
MicroRNA (miRNA) is a class of small RNAs of ~22nt which play essential roles in many crucial biological processes and numerous human diseases at post-transcriptional level of gene expression. It has been reve...
Cells sense chemical spatial gradients and respond by polarizing internal components. This process can be disrupted by gradient noise caused by fluctuations in chemical concentration.
Gillespie's stochastic simulation algorithm (SSA) for chemical reactions admits three kinds of elementary processes, namely, mass action reactions of 0th, 1st or 2nd order. All other types of reaction processes, ...
Modeling the Calvin-Benson cycle has a history in the field of theoretical biology. Anyone who intends to model this system will look at existing models to adapt, refine and improve them. With the goal to stud...
The family of TGF-β ligands is large and its members are involved in many different signaling processes. These signaling processes strongly differ in type with TGF-β ligands eliciting both sustained or transient ...
MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as dev...
Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconst...
Earlier, we identified proteins connecting different disease proteins in the human protein-protein interaction network and quantified their mediator role. An analysis of the networks of these mediators shows t...
The inference of biological networks from high-throughput data has received huge attention during the last decade and can be considered an important problem class in systems biology. However, it has been recog...
C4 plants such as corn and sugarcane assimilate atmospheric CO2 into biomass by means of the C4 carbon fixation pathway. We asked how PEP formation rate, a key step in the carbon fixation pathway, might work at a...