A Novel Approach to Knowledge Discovery and Representation in Biological Databases.

Extraction of motifs from biological sequences is among the frontier research issues in bioinformatics, with sequential patterns mining becoming one of the most important computational techniques in this area. A number of applications motivate the search for more structured patterns and concurrent protein motif mining is considered here. This paper builds on the concept of structural relation patterns and applies the Concurrent Sequential Patterns (ConSP) mining approach to biological databases. Specifically, an original method is presented using support vectors as the data structure for the extraction of novel patterns in protein sequences. Data modelling is pursued to represent the more interesting concurrent patterns visually. Experiments with real-world protein datasets from the UniProt and NCBI databases highlight the applicability of the ConSP methodology in protein data mining and modelling. The results show the potential for knowledge discovery in the field of protein structure identification. A pilot experiment extends the methodology to DNA sequences to indicate a future direction

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

Heat Stress and feeding strategies in meat-type chickens

Heat stress can induce hyperthermia in poultry. A reduction in heat load can be achieved by increasing the possibilities for dissipation, decreasing the level of heat production or by changing the thermal production pattern within a day. Strategies to reduce the negative effects of heat stress can be based on a specific feeding strategy, such as restricted feeding. Feed that is offered long enough before a hot period can ameliorate the harmful effects of high temperature. Another strategy may be to use choice feeding from different feed ingredients, rich in protein or in energy. With such self-selection, the chicken may adjust its intake of individual components, allowing the bird to optimise the heat load associated with the metabolism of the ingested nutrients. Additional promising strategies involve offering a choice between feeds with a different feed particle size or structure. A large particle size contributes to the development of the gastro-intestinal tract (GIT), especially the gizzard and the caeca. A large gizzard will maximize the grinding process and potentially ease digestion down the GIT, thereby reducing heat production associated with digestive processing. Also wet feeding may be profitable under heat stress conditions as well. Feeding wet diets may facilitate an increased water intake and larger particle sizes can limit water excretion in droppings, resulting in more water being available for evaporation during panting, hence cooling the bird. In conclusion, these feeding strategies may help to reduce heat production peaks, facilitate evaporative activity and/or decreases the heat load, resulting in beneficial effects on performance and health of the bird kept in more tropical areas worldwide

E-BioFlow: Different Perspectives on Scientific Workflows

We introduce a new type of workflow design system called\ud e-BioFlow and illustrate it by means of a simple sequence alignment workflow. E-BioFlow, intended to model advanced scientific workflows, enables the user to model a workflow from three different but strongly coupled perspectives: the control flow perspective, the data flow perspective, and the resource perspective. All three perspectives are of\ud equal importance, but workflow designers from different domains prefer different perspectives as entry points for their design, and a single workflow designer may prefer different perspectives in different stages of workflow design. Each perspective provides its own type of information, visualisation and support for validation. Combining these three perspectives in a single application provides a new and flexible way of modelling workflows

The mechanics of Arabidopsis seed germination

Germination is defined as the protrusion of the embryonic radicle through the seed coat layers (endosperm and testa). As the radicle elongates, the testa ruptures, followed by rupture of the endosperm. Arabidopsis seeds exhibit a two-step germination process with sequential rupture of the testa and endosperm. We are interested in exploring the physical process of germination. Whilst much effort has previously been placed on genetic networks, a mathematical approach for furthering the understanding of the physical/mechanical properties of germination has not yet been described. The Mathematics in Plant Sciences Study Group helped us to develop a better understanding of the problem. Several different mathematical models were generated for radicle growth and endosperm stretching. These models were developed on multiscale dimensions – looking at the organ, tissue and cellular levels. The outcomes of the study group have heightened our interest in the mechanical aspects of germination, and we are currently progressing with a grant proposal – a collaboration between the Schools of Biosciences and Engineering at the University of Nottingham, and a group from the Department of Biology at the University of Freiburg, Germany

Formal executable descriptions of biological systems

The similarities between systems of living entities and systems of concurrent processes may support biological experiments in silico. Process calculi offer a formal framework to describe biological systems, as well as to analyse their behaviour, both from a qualitative and a quantitative point of view. A couple of little examples help us in showing how this can be done. We mainly focus our attention on the qualitative and quantitative aspects of the considered biological systems, and briefly illustrate which kinds of analysis are possible. We use a known stochastic calculus for the first example. We then present some statistics collected by repeatedly running the specification, that turn out to agree with those obtained by experiments in vivo. Our second example motivates a richer calculus. Its stochastic extension requires a non trivial machinery to faithfully reflect the real dynamic behaviour of biological systems

Mathematical model of bursting in dissociated Purkinje neurons

In vitro, Purkinje cell behaviour is sometimes studied in a dissociated soma preparation in which the dendritic projection has been cleaved. A fraction of these dissociated somas spontaneously burst. The mechanism of this bursting is incompletely understood. We have constructed a biophysical Purkinje soma model, guided and constrained by experimental reports in the literature, that can replicate the somatically driven bursting pattern and which hypothesises Persistent Na+ current (INaP) to be its burst initiator and SK K+ current (ISK) to be its burst terminator