A framework for evolutionary systems biology

Background  

Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.     

<Emphasis FontCategory="NonProportional">permGPU</Emphasis>: Using graphics processing units in RNA microarray association studies

Background  

Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed.     

Comparison of two systems for long-term heart rate variability monitoring in free-living conditions - a pilot study

Objective  

A number of small portable systems that can measure HRV are available to address questions related to autonomic regulation in free-living subjects. However, ambulatory HRV measurements obtained through use of these systems have not previously been validated against standard clinical measurements such as Holter recordings. The objective of this study was to validate HRV obtained using a commonly used system, Actiheart, during occupational and leisure-time activities.     

A comparative approach for the investigation of biological information processing: An examination of the structure and function of computer hard drives and DNA

Background  

The robust storage, updating and utilization of information are necessary for the maintenance and perpetuation of dynamic systems. These systems can exist as constructs of metal-oxide semiconductors and silicon, as in a digital computer, or in the "wetware" of organic compounds, proteins and nucleic acids that make up biological organisms. We propose that there are essential functional properties of centralized information-processing systems; for digital computers these properties reside in the computer's hard drive, and for eukaryotic cells they are manifest in the DNA and associated structures.     

On the functional diversity of dynamical behaviour in genetic and metabolic feedback systems

Background  

Feedback regulation plays crucial roles in the robust control and maintenance of many cellular systems. Negative feedbacks are found to underline both stable and unstable, often oscillatory, behaviours. We explore the dynamical characteristics of systems with single as well as coupled negative feedback loops using a combined approach of analytical and numerical techniques. Particularly, we emphasise how the loop's characterising factors (strength and cooperativity levels) affect system dynamics and how individual loops interact in the coupled-loop systems.     

An integrated system for genetic analysis

Background  

Large-scale genetic mapping projects require data management systems that can handle complex phenotypes and detect and correct high-throughput genotyping errors, yet are easy to use.     

Isothermal micro calorimetry - a new method for MIC determinations: results for 12 antibiotics and reference strains of E. coli and S. aureus

Background  

Antimicrobial susceptibility testing of microorganisms is performed by either disc diffusion or broth dilution tests. In clinical use, the tests are often still performed manually although automated systems exist. Most systems, however, are based on turbidometric methods which have well-known drawbacks.     

Parameter estimation and inference for stochastic reaction-diffusion systems: application to morphogenesis in D. melanogaster

Background  

Reaction-diffusion systems are frequently used in systems biology to model developmental and signalling processes. In many applications, count numbers of the diffusing molecular species are very low, leading to the need to explicitly model the inherent variability using stochastic methods. Despite their importance and frequent use, parameter estimation for both deterministic and stochastic reaction-diffusion systems is still a challenging problem.     

Simple generation of site-directed point mutations in the <Emphasis Type="Italic">Escherichia coli</Emphasis> chromosome using Red<Superscript>®</Superscript>/ET<Superscript>®</Superscript> Recombination

Background  

Introducing point mutations into bacterial chromosomes is important for further progress in studies relying on functional genomics, systems- and synthetic biology, and for metabolic engineering. For many investigations, chromosomal systems are required rather than artificial plasmid based systems.     

MICE, a program to track and monitor animals in animal facilities

Background  

A growing number of laboratories are using the mouse as a model system in developmental biology as well as in molecular biology. Surprisingly, most of these laboratories do not have reliable computerized systems to track these animals, and the few commercial solutions available are expensive. We thus developed MICE (Mouse Information and Classification Entity), a program aimed at facilitating the monitoring of animals in animal facilities.     

Parameter estimation in biochemical systems models with alternating regression

Background  

The estimation of parameter values continues to be the bottleneck of the computational analysis of biological systems. It is therefore necessary to develop improved methods that are effective, fast, and scalable.     

Predicted class-I aminoacyl tRNA synthetase-like proteins in non-ribosomal peptide synthesis

Background  

Recent studies point to a great diversity of non-ribosomal peptide synthesis systems with major roles in amino acid and co-factor biosynthesis, secondary metabolism, and post-translational modifications of proteins by peptide tags. The least studied of these systems are those utilizing tRNAs or aminoacyl-tRNA synthetases (AAtRS) in non-ribosomal peptide ligation.     

Elementary signaling modes predict the essentiality of signal transduction network components

Background  

Understanding how signals propagate through signaling pathways and networks is a central goal in systems biology. Quantitative dynamic models help to achieve this understanding, but are difficult to construct and validate because of the scarcity of known mechanistic details and kinetic parameters. Structural and qualitative analysis is emerging as a feasible and useful alternative for interpreting signal transduction.     

Stochastic and deterministic multiscale models for systems biology: an auxin-transport case study

Background  

Stochastic and asymptotic methods are powerful tools in developing multiscale systems biology models; however, little has been done in this context to compare the efficacy of these methods. The majority of current systems biology modelling research, including that of auxin transport, uses numerical simulations to study the behaviour of large systems of deterministic ordinary differential equations, with little consideration of alternative modelling frameworks.     

Diffusive coupling can discriminate between similar reaction mechanisms in an allosteric enzyme system

Background  

A central question for the understanding of biological reaction networks is how a particular dynamic behavior, such as bistability or oscillations, is realized at the molecular level. So far this question has been mainly addressed in well-mixed reaction systems which are conveniently described by ordinary differential equations. However, much less is known about how molecular details of a reaction mechanism can affect the dynamics in diffusively coupled systems because the resulting partial differential equations are much more difficult to analyze.     

So what do we really mean when we say that systems biology is <Emphasis Type="Italic">holistic</Emphasis>?

Background  

An old debate has undergone a resurgence in systems biology: that of reductionism versus holism. At least 35 articles in the systems biology literature since 2003 have touched on this issue. The histories of holism and reductionism in the philosophy of biology are reviewed, and the current debate in systems biology is placed in context.