BMC Systems Biology

http://www.biomedcentral.com/1752-0509

List of Papers (Total 1,679)

Coordinated regulation of acid resistance in Escherichia coli

Background Enteric Escherichia coli survives the highly acidic environment of the stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. The first described system, AR1, does not require an external amino acid. Its mechanism has not been determined. The...

A computational method for the investigation of multistable systems and its application to genetic switches

Background Genetic switches exhibit multistability, form the basis of epigenetic memory, and are found in natural decision making systems, such as cell fate determination in developmental pathways. Synthetic genetic switches can be used for recording the presence of different environmental signals, for changing phenotype using synthetic inputs and as building blocks for higher...

The quality of metabolic pathway resources depends on initial enzymatic function assignments: a case for maize

Background As metabolic pathway resources become more commonly available, researchers have unprecedented access to information about their organism of interest. Despite efforts to ensure consistency between various resources, information content and quality can vary widely. Two maize metabolic pathway resources for the B73 inbred line, CornCyc 4.0 and MaizeCyc 2.2, are based on...

SParSE++: improved event-based stochastic parameter search

Background Despite the increasing availability of high performance computing capabilities, analysis and characterization of stochastic biochemical systems remain a computational challenge. To address this challenge, the Stochastic Parameter Search for Events (SParSE) was developed to automatically identify reaction rates that yield a probabilistic user-specified event. SParSE...

Unearthing the transition rates between photoreceptor conformers

Background Obtaining accurate estimates of biological or enzymatic reaction rates is critical in understanding the design principles of a network and how biological processes can be experimentally manipulated on demand. In many cases experimental limitations mean that some enzymatic rates cannot be measured directly, requiring mathematical algorithms to estimate them. Here, we...

Mathematical model on Alzheimer’s disease

Background Alzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the...

A method for automated pathogenic content estimation with application to rheumatoid arthritis

Background Sequencing technologies applied to mammals’ microbiomes have revolutionized our understanding of health and disease. Hence, to assess diseases’ progression as well as therapies longterm effects, the impact of maladies and drugs on the gut-intestinal (GI) microbiome has to be evaluated. Typical metagenomic analyses are run to associate to a condition (disease, therapy...

DGCA: A comprehensive R package for Differential Gene Correlation Analysis

Background Dissecting the regulatory relationships between genes is a critical step towards building accurate predictive models of biological systems. A powerful approach towards this end is to systematically study the differences in correlation between gene pairs in more than one distinct condition. Results In this study we develop an R package, DGCA (for Differential Gene...

Untargeted metabolomics unravels functionalities of phosphorylation sites in Saccharomyces cerevisiae

Background Coordinated through a complex network of kinases and phosphatases, protein phosphorylation regulates essentially all cellular processes in eukaryotes. Recent advances in proteomics enable detection of thousands of phosphorylation sites (phosphosites) in single experiments. However, functionality of the vast majority of these sites remains unclear and we lack suitable...

In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein-protein interaction networks

Background Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment...

In silico metabolic network analysis of Arabidopsis leaves

Background During the last decades, we face an increasing interest in superior plants to supply growing demands for human and animal nutrition and for the developing bio-based economy. Presently, our limited understanding of their metabolism and its regulation hampers the targeted development of desired plant phenotypes. In this regard, systems biology, in particular the...

BCM: toolkit for Bayesian analysis of Computational Models using samplers

Background Computational models in biology are characterized by a large degree of uncertainty. This uncertainty can be analyzed with Bayesian statistics, however, the sampling algorithms that are frequently used for calculating Bayesian statistical estimates are computationally demanding, and each algorithm has unique advantages and disadvantages. It is typically unclear, before...

Combining laboratory and mathematical models to infer mechanisms underlying kinetic changes in macrophage susceptibility to an RNA virus

Background Macrophages are essential to innate immunity against many pathogens, but some pathogens also target macrophages as routes to infection. The Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is an RNA virus that infects porcine alveolar macrophages (PAMs) causing devastating impact on global pig production. Identifying the cellular mechanisms that mediate PAM...

The potential for non-adaptive origins of evolutionary innovations in central carbon metabolism

Background Biological systems are rife with examples of pre-adaptations or exaptations. They range from the molecular scale – lens crystallins, which originated from metabolic enzymes – to the macroscopic scale, such as feathers used in flying, which originally served thermal insulation or waterproofing. An important class of exaptations are novel and useful traits with non...

Generalized method of moments for estimating parameters of stochastic reaction networks

Background Discrete-state stochastic models have become a well-established approach to describe biochemical reaction networks that are influenced by the inherent randomness of cellular events. In the last years several methods for accurately approximating the statistical moments of such models have become very popular since they allow an efficient analysis of complex networks...

Attractor landscape analysis of colorectal tumorigenesis and its reversion

Background Colorectal cancer arises from the accumulation of genetic mutations that induce dysfunction of intracellular signaling. However, the underlying mechanism of colorectal tumorigenesis driven by genetic mutations remains yet to be elucidated. Results To investigate colorectal tumorigenesis at a system-level, we have reconstructed a large-scale Boolean network model of the...

An efficient algorithm for identifying primary phenotype attractors of a large-scale Boolean network

Background Boolean network modeling has been widely used to model large-scale biomolecular regulatory networks as it can describe the essential dynamical characteristics of complicated networks in a relatively simple way. When we analyze such Boolean network models, we often need to find out attractor states to investigate the converging state features that represent particular...

The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus

Background The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this...

Quantifying differences in cell line population dynamics using CellPD

Background The increased availability of high-throughput datasets has revealed a need for reproducible and accessible analyses which can quantitatively relate molecular changes to phenotypic behavior. Existing tools for quantitative analysis generally require expert knowledge. Results CellPD (cell phenotype digitizer) facilitates quantitative phenotype analysis, allowing users to...

Identifying model error in metabolic flux analysis – a generalized least squares approach

Background The estimation of intracellular flux through traditional metabolic flux analysis (MFA) using an overdetermined system of equations is a well established practice in metabolic engineering. Despite the continued evolution of the methodology since its introduction, there has been little focus on validation and identification of poor model fit outside of identifying “gross...

Metabolic modeling of a chronic wound biofilm consortium predicts spatial partitioning of bacterial species

Background Chronic wounds are often colonized by consortia comprised of different bacterial species growing as biofilms on a complex mixture of wound exudate. Bacteria growing in biofilms exhibit phenotypes distinct from planktonic growth, often rendering the application of antibacterial compounds ineffective. Computational modeling represents a complementary tool to...

Information theoretic approaches for inference of biological networks from continuous-valued data

Background Characterising programs of gene regulation by studying individual protein-DNA and protein-protein interactions would require a large volume of high-resolution proteomics data, and such data are not yet available. Instead, many gene regulatory network (GRN) techniques have been developed, which leverage the wealth of transcriptomic data generated by recent consortia to...

Identification of key player genes in gene regulatory networks

Background Identifying the gene regulatory networks governing the workings and identity of cells is one of the main challenges in understanding processes such as cellular differentiation, reprogramming or cancerogenesis. One particular challenge is to identify the main drivers and master regulatory genes that control such cell fate transitions. In this work, we reformulate this...

The Arabidopsis phytohormone crosstalk network involves a consecutive metabolic route and circular control units of transcription factors that regulate enzyme-encoding genes

Background Phytohormone synergies and signaling interdependency are important topics in plant developmental biology. Physiological and genetic experimental evidence for phytohormone crosstalk has been accumulating and a genome-scale enzyme correlation model representing the Arabidopsis metabolic pathway has been published. However, an integrated molecular characterization of...

Dynamic optimization of biological networks under parametric uncertainty

Background Micro-organisms play an important role in various industrial sectors (including biochemical, food and pharmaceutical industries). A profound insight in the biochemical reactions inside micro-organisms enables an improved biochemical process control. Biological networks are an important tool in systems biology for incorporating microscopic level knowledge. Biochemical...