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High throughput screens with RNA interference technology enable loss-of-function analyses of gene activities in mammalian cells. While the construction of genome-scale shRNA libraries has been successful, resu...
Calmodulin is an important multifunctional molecule that regulates the activities of a large number of proteins in the cell. Calcium binding induces conformational transitions in calmodulin that make it specif...
Optimization aims to make a system or design as effective or functional as possible. Mathematical optimization methods are widely used in engineering, economics and science. This commentary is focused on appli...
The transcriptional regulator c-Myc is the most frequently deregulated oncogene in human tumors. Targeted overexpression of this gene in mice results in distinct types of lung adenocarcinomas. By using microar...
Signalling pathways relay information by transmitting signals from cell surface receptors to intracellular effectors that eventually activate the transcription of target genes. Since signalling pathways involv...
Several approaches, including metabolic control analysis (MCA), flux balance analysis (FBA), correlation metric construction (CMC), and biochemical circuit theory (BCT), have been developed for the quantitativ...
Analyzing the dynamics of insulin concentration in the blood is necessary for a comprehensive understanding of the effects of insulin in vivo. Insulin removal from the blood has been addressed in many studies. Th...
In recent years, stochastic descriptions of biochemical reactions based on the Master Equation (ME) have become widespread. These are especially relevant for models involving gene regulation. Gillespie’s Stoch...
As computational performance steadily increases, so does interest in extending one-particle-per-molecule models to larger physiological problems. Such models however require elementary rate constants to calcul...
Biological robustness results from redundant pathways that achieve an essential objective, e.g. the production of biomass. As a consequence, the biological roles of many genes can only be revealed through mult...
The development of complex biochemical models has been facilitated through the standardization of machine-readable representations like SBML (Systems Biology Markup Language). This effort is accompanied by the...
The amplification of signals, defined as an increase in the intensity of a signal through networks of intracellular reactions, is considered one of the essential properties in many cell signalling pathways. De...
Due to the growing amount of biological knowledge that is incorporated into metabolic network models, their analysis has become more and more challenging. Here, we examine the capabilities of the recently intr...
The complex yet flexible cellular response to pathogens is orchestrated by the interaction of multiple signalling and metabolic pathways. The molecular regulation of this response has been studied in great det...
The inverse problem of identifying the topology of biological networks from their time series responses is a cornerstone challenge in systems biology. We tackle this challenge here through the parameterization...
Systems genetic studies have been used to identify genetic loci that affect transcript abundances and clinical traits such as body weight. The pairwise correlations between gene expression traits and/or clinic...
Compendia of gene expression profiles under chemical and genetic perturbations constitute an invaluable resource from a systems biology perspective. However, the perturbational nature of such data imposes spec...
The Epidermal Growth Factor (EGF) receptor has been shown to internalize via clathrin-independent endocytosis (CIE) in a ligand concentration dependent manner. From a modeling point of view, this resembles an ...
Light and carbon are two important interacting signals affecting plant growth and development. The mechanism(s) and/or genes involved in sensing and/or mediating the signaling pathways involving these interact...
Stochasticity plays important roles in many molecular networks when molecular concentrations are in the range of 0.1 μ M to 10n M (about 100 to 10 copies in a cell). The chemical master equation provides a fundam...
The importance and power of isotope-based metabolic flux analysis and its contribution to understanding the metabolic network is increasingly recognized. Its application is, however, still limited partly due t...
Mathematical modeling is important to provide insight in the complicated pathway of RNA silencing. RNA silencing is an RNA based mechanism that is widely used by eukaryotes to fight viruses, and to control gen...
The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be ...
Modeling and simulation of cellular signaling and metabolic pathways as networks of biochemical reactions yields sets of non-linear ordinary differential equations. These models usually depend on several param...
The relationship between the regulatory design and the functionality of molecular networks is a key issue in biology. Modules and motifs have been associated to various cellular processes, thereby providing an...
Recent years has witnessed an increasing number of studies on constructing simple synthetic genetic circuits that exhibit desired properties such as oscillatory behavior, inducer specific activation/repression...
Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular c...
Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucle...
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 Esch...
Few genome-scale models of organisms focus on the regulatory networks and none of them integrates all known levels of regulation. In particular, the regulations involving metabolite pools are often neglected. ...
Male infertility is a major problem for mammalian reproduction. However, molecular details including the underlying mechanisms of male fertility are still not known. A thorough understanding of these mechanism...
In the bacterium Escherichia coli the transcriptional regulation of gene expression involves both dedicated regulators binding specific DNA sites with high affinity and also global regulators – abundant DNA archi...
Uncovering the operating principles underlying cellular processes by using 'omics' data is often a difficult task due to the high-dimensionality of the solution space that spans all interactions among the bio-...
One of the eminent opportunities afforded by modern genomic technologies is the potential to provide a mechanistic understanding of the processes by which genetic change translates to phenotypic variation and ...
Biochemical equilibria are usually modeled iteratively: given one or a few fitted models, if there is a lack of fit or over fitting, a new model with additional or fewer parameters is then fitted, and the proc...
The indispensability of certain genes in an organism is important for studies of microorganism physiology, antibiotic targeting, and the engineering of minimal genomes. Time and resource intensive genome-wide ...
The regulatory interactions between transcription factors (TF) and regulated genes (RG) in a species genome can be lumped together in a single directed graph. The TF's and RG's conform the nodes of this graph,...
We investigate the cycles in the transcription network of Saccharomyces cerevisiae. Unlike a similar network of Escherichia coli, it contains many cycles. We characterize properties of these cycles and their plac...
Data from high-throughput experiments of protein-protein interactions are commonly used to probe the nature of biological organization and extract functional relationships between sets of proteins. What has no...
Analysis of microarray data has been used for the inference of gene-gene interactions. If, however, the aim is the discovery of disease-related biological mechanisms, then the criterion for defining such inter...
Although a great deal is known about one gene or protein and its functions under different environmental conditions, little information is available about the complex behaviour of biological networks subject t...
Reconstruction of regulatory networks is one of the most challenging tasks of systems biology. A limited amount of experimental data and little prior knowledge make the problem difficult to solve. Although mod...
Obtaining quantitative predictions for cellular metabolic activities requires the identification and modeling of the physicochemical constraints that are relevant at physiological growth conditions. Molecular ...
Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative s...
The rapid accumulation of various network-related data from multiple species and conditions (e.g. disease versus normal) provides unprecedented opportunities to study the function and evolution of biological s...
The hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of tissues, including epithelial cells, on binding to the receptor tyrosine kinase c-Met. Abnormal c-Me...
Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting...
Autoantigens have been reported in a variety of tumors, providing insight into the interplay between malignancies and the immune response, and also giving rise to novel diagnostic and therapeutic concepts. Why...
The functions of a eukaryotic cell are largely performed by multi-subunit protein complexes that act as molecular machines or information processing modules in cellular networks. An important problem in system...
The Minimal Information Requested In the Annotation of biochemical Models (MIRIAM) is a set of guidelines for the annotation and curation processes of computational models, in order to facilitate their exchange a...