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The Zeeman Institute

Paul Brown

My background is in experimental biology, but my research interest today is in the development of user-friendly sustainable scientific software for data acquisition, analysis and modelling.

At the present, my time is split between the Zeeman Institute and the Bioinformatics Research Technology Platform.

My work has been funded by a variety of sources including EPSRC, BBSRC, the European Union, The Wellcome Trust and The Bill and Melinda Gates Foundation.

Current projects in the Zeeman Institute

  • The HATMEPP project. This is an international, multidisciplinary research project funded by the Bill and Melinda Gates Foundation to support planning and implementation of gambiese HAT (sleeping sickness) interventions through the use of mathematical modelling predictions and economic analyses. My role is the design and implementation of a web-based user interface to allow policy makers to easily access our predictive models.
  • A web-based framework for bioinformatics tools, a framework for the automated generation of richly featured HTML interfaces for simple command line based applications.
  • BITERS, the Bite Incidence Tool for Enhanced Rabies Surveillance, a project to improve surveillance and reduce the human health impact of rabies in dogs in the Philippines. BITERS is an electronic record collection app for Android, designed to be used on mobile devices out in the field. The collected data can subsequently be uploaded to a web-based platform for analysis and visualisation in "real-time".
  • Inference of disease transmission in conjunction with the Neglected Tropical Diseases Modelling Consortium, an international collaboration lead by University of Warwick.
  • Peptide Identification from Combinatorial Peptide Libraries (PICPL). This web tool uses readouts of a powerful peptide scanning method called combinatorial peptide libraries. It scans databases of human proteins and proteins from various pathogenic micro-organisms in order to determine which peptides are most likely to have stimulated a particular immune response. This tool has been produced in conjunction with the Systems Immunity Research Institute, University of Cardiff.

    Past projects

    • Perturbation Theory Toolbox for Systems (PeTTSy), a package for MATLAB which implements a wide array of techniques for the perturbation theory and sensitivity analysis of large and complex, high dimensional, ordinary differential equation based models of regulatory and signalling systems. PeTTSy offers the user the ability to explore the effect of a range of parameter perturbations on a range of model outputs and visualise complex, multi-dimensional data. PeTTSy can be downloaded here.
    • Celltracker image analysis software.
    • Causal Structure Identification (CSI), a nonparametric Bayesian approach to network inference from multiple perturbed time series gene expression data.
    • VBSSM GUI. This is a graphical front end for the Variational Bayesian State Space Modelling (VBSSM) toolbox for Matlab, by Matthew J Beal, which is used to infer gene networks from time series expression data. The GUI provides a user friendly interface for the import and filtering of expression data and presentation of the results, including the generation of network files for the open source network visualisation tool Cytoscape. It can also parallelise the algorithm if the user has access to the Matlab Parallel Computing Toolbox, and offload analysis to a remote server running the Matlab Distributed Computing Server. VBSSMGUI can be dowloaded from here
    • Spectrum Resampling, a period fitting algorithm with a graphical front end, which imports periodic time series data from Microsoft Excel xls files. This software is available as a Matlab toolbox or a standalone binary for Windows or Mac OS X, and can be dowloaded from here.
    • Circadian Modelling. A software package for running ordinary differential equation models of the gene networks underlying the circadian oscillator. The user can replicate complex experimental protocols, with the results being output as a Microsoft Excel workbook.
    • BRASS, the Biological Rhythms Analysis Package. A Microsoft Excel workbook macro for the import and analysis of experimental gene expresion data from a variety of common platforms. BRASS will import data from most of the data acquisition packages commonly used in plant circadian research, such as Kujata, Metamorph, Night Owl and Topcount, and also from a generic block of data. Our program will then automatically fit period, phase and amplitude values using a Fast Fourier Transform method, and import the results back into MS Excel. BRASS also contains functions to perform statistical analysis of results, and to enable the rapid production of charts and graphs.
    • Visualisation tools written for Matlab which show the dynamic behaviour of oscillating gene networks. Model outputs can be plotted as 2D or 3D limit cycles. Model parameters can be altered dynamically and the effect on output immediately observed.

    Publications describing my software

    • Whalley, T, Dolton, G, Brown, PE, Wall, A, Wooldridge, L, van den Berg, H, Fuller, A, Hopkins, JR, Crowther, MD, Attaf, M, Knight, RR, Cole, DK, Peakman, M, Sewell, AK and Szomolay B (2020) GPU-Accelerated Discovery of Pathogen-Derived Molecular Mimics of a T-Cell Insulin Epitope. Frontiers in Immunology. 11:296. doi: 10.3389/fimmu.2020.00296
    • Stolk, W. A., Prada, J. M., Smith, M. E., Kontoroupis, P., de Vos, A. S., Touloupou, P., Irvine, M. A., Brown, P., Subramanian, S., Michael, M. K. E., Hollingsworth, T. D., de Vlas, S. J. (2018). Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models. Clinical Infectious Diseases 66(4): S260–S266 doi: 10.1093/cid/ciy003
    • Krzysztof Polanski, Bo Gao, Sam A. Mason, Paul Brown, Sascha Ott, Katherine J. Denby and David L. Wild. (2017). Bringing numerous methods for expression and promoter analysis to a public cloud computing service. Bioinformatics 34(5): 884-886 doi: 10.1093/bioinformatics/btx692
    • Szomolay, B., Liu, J., Brown, P. E., Miles, J. J., Clement, M., Llewellyn-Lacey, S., Dolton, G., Ekeruche-Makinde, J., Lissina, A., Schauenburg, A. J., Sewell, A. K., Burrows, S. R., Roederer, M., Price, D. D., Wooldridge, L. & van den Berg, H. A. (2016). Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors. Immunology and Cell Biology 94(6): 573-582 doi: 10.1038/icb.2016.12
    • Domijan, M., Brown, P. E., Shulgin, B. V, & Rand, D. A. (2016). PeTTSy: a computational tool for perturbation analysis of complex systems biology models. BMC Bioinformatics 17:124 doi: 10.1186/s12859-016-0972-2
    • Penfold, C. A., Shifaz, A., Brown, P. E., Nicolson, A., & Wild, D. L. (2015). CSI: a nonparametric Bayesian approach to network inference from multiple perturbed time series gene expression data. Statistical Applications in Genetics and Molecular Biology. 14(3): 307–310 doi: 10.1515/sagmb-2014-0082.
    • Brown, P., Baxter, L,. Hickman, R., Beynon, J., Moore, J. D., & Ott, S. (2013). MEME-LaB: motif analysis in clusters. Bioinformatics 29(13):1696-7. doi: 10.1093/bioinformatics/btt248.

    • Christopher A. Penfold, Paul E. Brown, Neil D. Lawrence, Alastair S. H. Goldman (2012). Modelling Meiotic Chromosomes Indicates a Size Dependent Contribution of Telomere Clustering and Chromosome Rigidity to Homologue Juxtaposition. PLoS Comput Biol 8(5): e1002496. doi:10.1371/journal.pcbi.1002496

    • Edwards, K. D., Akman, O. E., Knox, K., Lumsden, P. J., Thomson, A. W., Brown, P. E., Pokhilko, A., Kozma-Bognar, L., Nagy, F., Rand, D. A., & Millar, A. J. (2010). Quantitative analysis of regulatory flexibility under changing environmental conditions. Molecular Systems Biology 6:424 doi:10.1038/msb.2010.81
    • Picot, E., Krusche, P., Tiskin, A., CarrĂ©, I. & Ott, S. (2010). Evolutionary Analysis of Regulatory Sequences (EARS) in Plants. Plant Journal doi: 10.1111/j.1365-313X.2010.04314.x
    • Akman, O. E., Rand, D. A., Brown, P. E. & Millar, A. J. (2010). Robustness from flexibility in the fungal circadian clock. BMC Systems Biology 4:88 doi:10.1186/1752-0509-4-88
    • Salazar, J. D., Saithong, T., Brown, P. E., Foreman, J., Locke, J. C. W., Halliday, K. J., CarrĂ©, I. A., Rand, D. A. & Millar, A. J. (2009). Prediction of photoperiodic regulators from quantitative gene circuit models. Cell 139: 1170-1179
    • Hall, A. & Brown, P. E. (2007) Monitoring Circadian Rhythms in Arabidopsis thaliana Using Luciferase Reporter Genes. In Methods in circadian Biology. Totowa, Humana Press.
    • Darrah, C., Taylor, B. L., Edwards, K. D., Brown, P. E., Hall, A. & McWatters H. G. (2006) Analysis of Phase of LUCIFERASE Expression Reveals Novel Circadian Quantitative Trait Loci in Arabidopsis. Plant Physiology 140: 1464-1474
    • Hall, A. & Brown, P. E. (2006). Monitoring Circadian Rhythms in Arabidopsis thaliana using Luciferase Reporter Genes. In Circadian Rhythms Methods and Protocols, Rosato, E. (Ed), Humana Press
    • Southern, M. M., Brown, P. E. & Hall, A. (2006). Luciferases as Reporter Genes. In Arabidopsis Protocols, Salinas, J. & Sanchez-Serrano, J. J. (Eds), Humana Press
    • Locke J.C.W., Southern M.M., Kozma-Bognar L., Hibberd V., Brown P.E., Turner M.S. & Millar A.J. (2005) Extension of a genetic network model by iterative experimentation and mathematical analysis. Molecular Systems Biology, 1:13. doi: 10.1038/msb410001


    Other publications

    • Brown, P. E. & Dale, N. (2002a). Modulation of K+ currents in Xenopus spinal neurones by p2y2 receptors: a role for ATP and ADP in motor pattern generation. Journal of Physiology 540: 843-850
    • Brown, P. E. & Dale, N. (2002b). Spike-independent release of ATP from Xenopus spinal neurones evoked by activation of glutamate receptors. Journal of Physiology 540: 851-860
    • Brown, P. E. & Dale, N. (2000a). Adenosine A1 receptors modulate high voltage-activated Ca2+ currents and motor pattern generation in the Xenopus embryo. Journal of Physiology 525: 655-667
    • Brown, P.E. & Dale, N. (2000b). Activation of presynaptic glutamate receptors evokes ATP release from Xenopus spinal pre-motor interneurones. Journal of Physiology 528P: 63
    • Brown, P.E. & Dale, N. (2000c). Release of ATP from spinal neurones mediated by pre-synaptic glutamate receptors. Society for Neuroscience Abstracts 26: 404
    • Brown, P.E. & Dale, N (1999). Purinergic modulation of ionic currents in Xenopus spinal neurones. Journal of Physiology 515P: 115P
    • Brown, P. E. & Anderson, M. (1999). Factors affecting the ovipositor probing response of Trybliographa rapae (Hymenoptera: Cynipidae), a parasitoid of the cabbage root fly. Entomologia Experimentalis et Applicata 93: 217-225
    • Brown, P. E., Frank, C. P., Groves, H. L. & Anderson, M. (1998). Spectral sensitivity and visual conditioning in the parasitoid wasp Trybliographa rapae (Hymenoptera: Cynipidae). Bulletin of Entomological Research 88: 239-245
    • Brown, P. E. & Anderson, M. (1998). Morphology and ultrastructure of the sense organs of the ovipositor of Trybliographa rapae (Hymenoptera: Cynipidae), a parasitoid of the cabbage root fly. Journal of Insect Physiology 44: 1017-1025
    • King, F. C. & Brown, P. E. (1997). Is experience important? A behavioural and electrophysiological study on the parasitoid wasp Trybliographa rapae (Hymenoptera: Cynipidae). Abstracts of the British Ecological Society Winter and Annual General Meeting, December 1997
    • Brown, P. E. & Anderson, M. (1996). Spectral sensitivity of the compound eye of the cabbage root fly, Delia radicum (Diptera: Anthomyiidae). Bulletin of Entomological Research 86: 337-342
    • Anderson, M., Brown, P. E. & Skilbeck, C. A. (1994). Sensory ecology of insect parasitoids. Abstracts of the British Ecological Society Winter and Annual General Meeting, December 1994, pp. 70

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