BioLayout Express3D: A Community Resource for the Network Visualisation and Analysis of Biological Data and Pathways

Biological data is increasingly complex and large-scale. Genome sequencing and other high-throughput technologies have provided us with a parts-list of life, together with a wealth of information about how these components interact with each other. Humans are inherently visual and representing this information in the form of graphs and graphics is an extremely useful aid to our understanding of its innate complexity. Tools that assist biologists in their ability to visualise, analyse and interpret biological systems are therefore potentially of great utility. Both applicants have a long-standing interest in the analysis of biological data and have been involved in the development of computer programs for its visualisation and analysis. In particular, with support from the BBSRC and Wellcome Trust, we have co-developed a powerful network analysis tool, BioLayout Express3D. This software has proved highly useful to applicant's research and also popular with the wider academic community. We therefore seek to continue to expand its functionality into new areas, thereby maintaining its position at the cutting-edge of the visualisation and interpretation of biological systems. This project capitalises on the existing collaborative work and aims to explore new areas of computation, biology and visualisation with both participating laboratories scoping, testing and validating developments prior to their release to the wider community. Our first aim is to refine and expand the existing interface of BioLayout Express3D to enable it to read and process biological data from a wide variety of sources. We also seek to improve the quality of the user interface and its analytical potential, as well as to provide improved support and training its users. Secondly we aim to develop its capabilities to be deployed for the visualisation and analysis of data derived from other sources e.g. EBI databases, and for providing access to networks of analysed data. Thirdly, we wish to further explore the potential to use this tool for the modelling and visualisation of biological pathways. Finally, with the rapid pace of development of programming languages and advanced computer hardware, we will explore the potential to harness the power these developments for improving the power and speed of network analyses. We believe that the proposed project will allow us to deliver a cutting-edge tool addressing the shortcomings of currently available commercial and academic systems. The rapid growth of 3D graphics hardware and computer speed allows us to develop these tools for regular desktop computers, yet still allow the analysis of datasets an order of magnitude larger than other systems. BioLayout Express3D will allow biologists to contextualise and visualise their data in an unprecedented manner and we hope it will be a significant boon to the wider academic community.

The availability of complete genome sequences and technologies that allow us to characterise the activity of the genes they encode, protein interaction partners and pathways has greatly contributed to our appreciation of biological systems. However, in order to understand the large amounts of data generated by these functional genomics and proteomics platforms and the complexity of biological systems, there has been increasing emphasis on developing new methods and tools in computational and systems biology, to allow for the comprehensive mapping of cellular and molecular networks. However, one of the main difficulties we currently face is how best to integrate and visualise these disparate data types and use the information to better understand biological systems in health and disease. Over the last few years we have developed the successful BioLayout Express3D application with support from the BBSRC and Wellcome Trust. We now seek funding to maintain this software at the cutting-edge of this field and to explore new areas of analysis and biology. We intend to expand and develop the basic interface to include parsing of most common biological datasets, such as networks and pathways from the standard exchange formats, as well as its built-in analytical capabilities. We also seek to expand the paradigm of network visualisation to capture both the spatial and temporal arrangements of genes, proteins and other molecules. Utilising the applicant's expertise in the analysis genomics data, we will further develop the application for the visualisation and interpretation of complex biological datasets in an intuitive and fast 3-Dimensional interface. In so doing we will support others in the deployment and use of the tool.

With the recent advent and accessibility of low cost, high throughput omics analysis platforms many are now employing these technologies for their field of interest. As a result, researchers whose interests may have traditionally been focused on one or a small number of biological components are now often faced with analysing enormous amounts of data pertaining to the activity of many thousands of genes and proteins and their interactions in the cell. Large datasets are inevitably complex and many aspects of data analysis remain frustrating, even for those skilled in the art. Indeed, despite a plethora of analytical and statistical approaches to deal with 'omics data, the analysis of large datasets still presents a significant challenge and as a result much of the potential value of omics data is frequently never realised. BioLayout Express3D has been developed as a stand alone application, primarily for the visualisation and analysis of large network graphs. It was originally developed to provide an improved method for visualisation and analysis of microarray gene expression data. Using this tool we have been able explore a number of large and complicated datasets in a way not possible by conventional analytical techniques. It has facilitated the acquisition of new insights into the nature of complex data derived from complex diseases and allowed us to identify potential biomarkers and therapeutic targets of disease. Future developments to the tool will also allow us to support the analysis of other data types and in so doing potentially allow improved interpretation of these data. In our opinion BioLayout Express3D is now the most advanced tool available in the commercial or academic domains for the rendering and analysis of large network graphs derived not only from omics data but in principle relationships between any entities or concepts. It has an extensive range of built in tools to enable the user to modify the visual characteristics of the networks, select nodes, view their identity and associated data, and to perform sophisticated analyses of network topology. It has also been designed to be easy to use by others and to work on all standard computational platforms. To this end we have already gone to considerable lengths to support others in its deployment and use through the development of a comprehensive website and publication of a detail protocol. The current application will allow us to further improve the functionality of BioLayout Express3D and support its growing user base across different academic communities with improved training opportunities and online support. In so doing, we hope its analytical capabilities will allow others to capitalise on their often considerable investment in data generation and help drive their work forward. It also perhaps worthy of mention that over the last year 21% of hits on the website were recorded as coming from commercial organisations perhaps reflecting the potential application of this type of analyses in commercial domain.