A text-mining system for extracting metabolic reactions from full-text articles

Background: Increasingly biological text mining research is focusing on the extraction of complex relationships relevant to the construction and curation of biological networks and pathways. However, one important category of pathway—metabolic pathways—has been largely neglected. Here we present a relatively simple method for extracting metabolic reaction information from free text that scores different permutations of assigned entities (enzymes and metabolites) within a given sentence based on the presence and location of stemmed keywords. This method extends an approach that has proved effective in the context of the extraction of protein–protein interactions. Results: When evaluated on a set of manually-curated metabolic pathways using standard performance criteria, our method performs surprisingly well. Precision and recall rates are comparable to those previously achieved for the well-known protein-protein interaction extraction task. Conclusions: We conclude that automated metabolic pathway construction is more tractable than has often been assumed, and that (as in the case of protein–protein interaction extraction) relatively simple text-mining approaches can prove surprisingly effective. It is hoped that these results will provide an impetus to further research and act as a useful benchmark for judging the performance of more sophisticated methods that are yet to be developed

Towards a lightweight generic computational grid framework for biological research

Background: An increasing number of scientific research projects require access to large-scale computational resources. This is particularly true in the biological field, whether to facilitate the analysis of large high-throughput data sets, or to perform large numbers of complex simulations – a characteristic of the emerging field of systems biology. Results: In this paper we present a lightweight generic framework for combining disparate computational resources at multiple sites (ranging from local computers and clusters to established national Grid services). A detailed guide describing how to set up the framework is available from the following URL: http://igrid-ext.cryst.bbk.ac.uk/portal_guide/. Conclusion: This approach is particularly (but not exclusively) appropriate for large-scale biology projects with multiple collaborators working at different national or international sites. The framework is relatively easy to set up, hides the complexity of Grid middleware from the user, and provides access to resources through a single, uniform interface. It has been developed as part of the European ImmunoGrid project

Regenerating the rangelands

Parts of Western Australia\u27s rangelands have been degraded by inappropriately high stocking rates, often associated with large numbers of native or feral animals, poor seasonal plant growth, or the ravages of cyclones, floods or fire. Today, most pastoralists are keen to rehabilitate the degradation of the past, as indicated by the proliferation of Land Conservation Districts (LCDs) throughout the pastoral zones. There is no \u27quick fix\u27 to regenerating the rangelands. It may take many years to achieve the desired result

Utilities for high-throughput analysis of B-cell clonal lineages

There are at present few tools available to assist with the determination and analysis of B-cell lineage trees from next-generation sequencing data. Here we present two utilities that support automated large-scale analysis and the creation of publication-quality results. The tools are available on the web, and are also available for download so that they can be integrated into an automated pipeline. Critically, and in contrast to previously published tools, these utilities can be used with any suitable phylogenetic inference method and with any antibody germline library, and hence are species-independent

The geochemistry and evolution of the Lizard Complex, Cornwall

The Lizard Complex consists of a poorly exposed assemblage of serpentinites, gabbros, amphibolites, basic dykes, metasediments and gneisses. As an alternative approach to conventional mapping of the inland area, the geochemistry of the residual soils of the area are used to identify the underlying lithologies. Using multi-element geochemical data obtained by X-ray fluorescence spectrometry, an identification scheme is established which allows the recognition of over a dozen mappable units with a high rate of success. This scheme evolved from a training set of samples collected during an orientation survey from areas of undisputed geology immediately adjacent to coastal exposure. At approximately 250 sites it has been possible to confirm the geological predictions directly against material obtained from the base of power auger holes. A non-hierarchical K-means clustering technique is developed and used to recluster data from over 800 samples into gabbroic and ultrabasic groups. The results of this classification produced more sensitive discriminatory parameters which in turn are used on 1500+ samples collected during the project. The soil identification procedure combines the use of a variety of numerical techniques and the algorithm designed to use them operates in a sequential manner. The most distinct units are identified at an early stage whilst those samples which are less distinct chemically take longer to isolate and as a final stage of treatment are separated using a modified K-means technique. This approach to mapping has allowed the recognition of units not found outcropping on coastal sections and for an improved geological map of the Lizard Complex to be drawn. In particular the Crousa gabbro is shown to be a smaller body than previously considered and to comprise several different bodies. As a result of this work the evolutionary history of the Complex is revised

Scaling up: Achieving a breakthrough in adult learning with technology

The first report commissioned by Ufi Charitable Trust. It investigates opportunities for and barriers to the application of digital technology to adult learning. It focuses on possible ways to transform the UK’s vocational education and training system, identifying three main priorities for funding by the Ufi Charitable Trust: * increasing the capability of those involved in running the vocational learning system * exploiting networks to bring together learners, learning content and learning professionals * harnessing computers to support individualised and differentiated learning

The geochemistry and evolution of the Lizard Complex, Cornwall

The Lizard Complex consists of a poorly exposed assemblage of serpentinites, gabbros, amphibolites, basic dykes, metasediments and gneisses. As an alternative approach to conventional mapping of the inland area, the geochemistry of the residual soils of the area are used to identify the underlying lithologies. Using multi-element geochemical data obtained by X-ray fluorescence spectrometry, an identification scheme is established which allows the recognition of over a dozen mappable units with a high rate of success. This scheme evolved from a training set of samples collected during an orientation survey from areas of undisputed geology immediately adjacent to coastal exposure. At approximately 250 sites it has been possible to confirm the geological predictions directly against material obtained from the base of power auger holes. A non-hierarchical K-means clustering technique is developed and used to recluster data from over 800 samples into gabbroic and ultrabasic groups. The results of this classification produced more sensitive discriminatory parameters which in turn are used on 1500+ samples collected during the project. The soil identification procedure combines the use of a variety of numerical techniques and the algorithm designed to use them operates in a sequential manner. The most distinct units are identified at an early stage whilst those samples which are less distinct chemically take longer to isolate and as a final stage of treatment are separated using a modified K-means technique. This approach to mapping has allowed the recognition of units not found outcropping on coastal sections and for an improved geological map of the Lizard Complex to be drawn. In particular the Crousa gabbro is shown to be a smaller body than previously considered and to comprise several different bodies. As a result of this work the evolutionary history of the Complex is revised

Investigating substitutions in antibody–antigen complexes using molecular dynamics: a case study with broad-spectrum, Influenza A antibodies

In studying the binding of host antibodies to the surface antigens of pathogens, the structural and functional characterization of antibody–antigen complexes by X-ray crystallography and binding assay is important. However, the characterization requires experiments that are typically time consuming and expensive: thus, many antibody–antigen complexes are under-characterized. For vaccine development and disease surveillance, it is often vital to assess the impact of amino acid substitutions on antibody binding. For example, are there antibody substitutions capable of improving binding without a loss of breadth, or antigen substitutions that lead to antigenic escape? The questions cannot be answered reliably from sequence variation alone, exhaustive substitution assays are usually impractical, and alanine scans provide at best an incomplete identification of the critical residue–residue interactions. Here, we show that, given an initial structure of an antibody bound to an antigen, molecular dynamics simulations using the energy method molecular mechanics with Generalized Born surface area (MM/GBSA) can model the impact of single amino acid substitutions on antibody–antigen binding energy. We apply the technique to three broad-spectrum antibodies to influenza A hemagglutinin and examine both previously characterized and novel variant strains observed in the human population that may give rise to antigenic escape. We find that in some cases the impact of a substitution is local, while in others it causes a reorientation of the antibody with wide-ranging impact on residue–residue interactions: this explains, in part, why the change in chemical properties of a residue can be, on its own, a poor predictor of overall change in binding energy. Our estimates are in good agreement with experimental results—indeed, they approximate the degree of agreement between different experimental techniques. Simulations were performed on commodity computer hardware; hence, this approach has the potential to be widely adopted by those undertaking infectious disease research. Novel aspects of this research include the application of MM/GBSA to investigate binding between broadly binding antibodies and a viral glycoprotein; the development of an approach for visualizing substrate–ligand interactions; and the use of experimental assay data to rescale our predictions, allowing us to make inferences about absolute, as well as relative, changes in binding energy