BioLayout Express3D: A Community Resource for the Network Visualisation and Analysis of Biological Data and Pathways
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
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.
Technical Summary
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.
Planned Impact
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.
Publications
Alibhai J
(2016)
Distribution of Misfolded Prion Protein Seeding Activity Alone Does Not Predict Regions of Neurodegeneration.
in PLoS biology
Auffret MD
(2017)
Identification, Comparison, and Validation of Robust Rumen Microbial Biomarkers for Methane Emissions Using Diverse Bos Taurus Breeds and Basal Diets.
in Frontiers in microbiology
Baillie JK
(2018)
Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.
in PLoS computational biology
Bush SJ
(2018)
Network analysis of the social and demographic influences on name choice within the UK (1838-2016).
in PloS one
Clark EL
(2017)
A high resolution atlas of gene expression in the domestic sheep (Ovis aries).
in PLoS genetics
Doig TN
(2013)
Coexpression analysis of large cancer datasets provides insight into the cellular phenotypes of the tumour microenvironment.
in BMC genomics
Donaldson DS
(2015)
Reciprocal regulation of lymphoid tissue development in the large intestine by IL-25 and IL-23.
in Mucosal immunology
FANTOM Consortium And The RIKEN PMI And CLST (DGT)
(2014)
A promoter-level mammalian expression atlas.
in Nature
Ford CA
(2015)
Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.
in Current biology : CB
Description | BioLayout Express3D was designed for the rapid discovery of patterns and interactions within what is often called big data. In biology, there is a vast amount of this data being generated by modern analysis platforms and this tool allows users to gain insights from it. One of its key features is the ability to generate and explore correlation graphs of numerical matrices. This was originally designed for the analysis of gene expression data but is finding an application in the analysis of data from other analysis platforms e.g. multiparametric flow cytometry, genotyping, microbiome, proteomics, metagenomics etc. |
Exploitation Route | For nearly 10 years we produced and maintain BioLayout Express3D, a powerful tool for use of others in their research endeavours. There is a growing number of publications that have used BioLayout not only from our group but also from others. More still are beginning to change over to the newer commercial version of this tool called Graphia Professional, sold by Kajeka Ltd a company originally set up to capitalise on the BioLayout IP and develop new network analysis tools for use in other sectors. The company is now developing the next generation of software for network analysis, which is primarily designed for the biology sector but will have applications elsewhere. |
Sectors | Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
URL | http://www.biolayout.org/about/publications/ |
Description | The release of this tool as open-source software has allowed others in the academic community and beyond making use of its unique analytical capabilities for their own research. The numbers of scientists using this program worldwide are increasing (currently the program is being used 3,000-4,000 times per month) and there are a growing list of publications where the tool has been employed. Our Nature Protocols paper describing network analysis of gene expression data has been cited 248 times and the original paper describing BioLayout Express3D 221 times (Google scholar, March 2018) More recently a company Kajeka Ltd. (www.kajeka.com) has been founded to exploit this technology in the bioscience sector and beyond. Kajeka further developed the codebase of BioLayout and sold it for a number of years as a tool called Graphia Professional. With the release of the company's new network analysis tool called simply Graphia which incorporates and improves upon many of the ideas developed in BioLayout, Graphia Professional will return to being open source and free but maintained by the company (https://kajeka.com/graphia-professional/). |
Sector | Agriculture, Food and Drink,Creative Economy,Digital/Communication/Information Technologies (including Software),Environment,Pharmaceuticals and Medical Biotechnology |
Impact Types | Societal,Economic |
Title | Network analysis of short read sequencing data |
Description | The method developed under this grant supports the visualisation and analysis of short read sequencing data. Paper describing this work submitted. |
Type Of Material | Improvements to research infrastructure |
Provided To Others? | No |
Impact | None as yet |
URL | http://seq-graph.roslin.ed.ac.uk/ |
Title | Pathway modelling app |
Description | There is a need for formalised diagrams that both summarise current biological pathway knowledge and support modelling approaches that explain and predict their behaviour. Here, we present a new, freely available modelling framework that includes a biologist friendly pathway modelling language (mEPN), a simple but sophisticated method to support model parameterisation using available biological information; a stochastic flow algorithm that simulates the dynamics of pathway activity; and a 3-D visualisation engine that aids understanding of the complexities of a system's dynamics. We present example pathway models that illustrate of the power of approach to depict a diverse range of systems. |
Type Of Material | Model of mechanisms or symptoms - in vitro |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | This approach has been used to model a range of biological systems and we are slowly seeing in an increasing number of people adopting the method. |
URL | https://www.virtuallyimmune.org/ |
Title | BioLayout Express3D |
Description | BioLayout Express3D is a powerful tool for the visualization and analysis of network graphs. Network-based approaches are becoming increasingly popular for the analysis of complex systems of interaction and high dimensional data. Networks can be produced from a wide variety of relationships between entities. In biology this includes the interactions between individuals, disease transmission, sequence similarity, metabolic pathways, protein interactions, pathways, regulatory cascades, gene expression, clinical data. This tool represents the product of over 15 years research and development and uses a combination of high end 3D graphics, algorithms and user-friendly graphical interfaces to allow the user to explore and better analyse their data. |
Type Of Material | Data analysis technique |
Year Produced | 2007 |
Provided To Others? | Yes |
Impact | The website currently receives hits from approx. 700 users a month from around the globe and is used 1500-2000 times a month. This tool has been used in analyses that have contributed to over 40 publications. The technology and know how developed is currently en route to being commercialised and developed further by a new spin out company called Kajeka. |
URL | http://www.biolayout.org/ |
Title | Virtually Immune |
Description | Virtually Immune is a resource that aims to support the graphical and computational modelling of immune pathways. The tools and resources presented there are primarily designed for biologists, both to use and to allow them to develop their own models of systems of interest to them. Virtually Immune introduces: a standardised system for presenting pathway knowledge a user-friendly platform for modelling pathway resources which capture and collate information from hundreds of papers a platform for knowledge exchange within the scientific community |
Type Of Material | Computer model/algorithm |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | As a result of setting up this website as part of the phase 1 of the NCR's Crack it challenge we are beginning to guide people to it as a resource for our modelling efforts. Two papers in preparation describing the tools and our modelling approach. |
URL | http://www.virtuallyimmune.org/ |
Title | macrophages.com |
Description | Macrophages.com is an online resource for those interested in macrophages and their role as major effector cells in innate and adaptive immunity. This website is designed to act as a centralised resource for the worldwide community of scientists interested in different aspects of macrophage biology. Included here are: Collections of macrophage images in different tissues Expression datasets and transcriptional analyses Analysis of protein expression in macrophages A gene-centered information portal for macrophage-expressed genes Macrophage pathway resources Curated key publications and reviews on aspects of macrophage biology Useful online resources News and events |
Type Of Material | Database/Collection of data |
Year Produced | 2009 |
Provided To Others? | Yes |
Impact | This site is currently receiving hits from over a 1,00 unique users per week. |
URL | http://www.macrophages.com/ |
Description | BioLayout Express3D project |
Organisation | EMBL European Bioinformatics Institute (EMBL - EBI) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Together we have worked as a team in developing the BioLayout tool with almost all of the coding has been performed in Edinburgh. |
Collaborator Contribution | Advice, shared publications, ideas. |
Impact | Outcomes from this work include the tool itself, numerous publications by ourselves and others. The original paper published in PLoS Comp Biol (2007) has been cited 243 times and the Nature Protocols paper (2009) has been cited 239 times (Google Scholar, Feb 2019). This was a multidisciplinary collaboration involving biologists, computer scientists, software engineers and mathematicians.The codebase for this software was licensed from the University of Edinburgh by Kajeka Ltd a UoE spinout company (www.kajeka.com). |
Start Year | 2006 |
Title | BioLayout Express3D |
Description | This is a network analysis tool and represents the product of over 15 years research and development. It uses a combination of high end 3D graphics, algorithms and user-friendly graphical interfaces to allow the user to explore and better analyse their data. |
IP Reference | |
Protection | Copyrighted (e.g. software) |
Year Protection Granted | 2014 |
Licensed | Yes |
Impact | The website currently receives hits from approx. 700 users a month from around the globe and is used 1500-2000 times a month. This tool has been used in analyses that have contributed to over 40 publications. The technology and know how developed is currently en route to being commercialised and developed further by a new spin out company called Kajeka. |
Title | BioLayout Express3D |
Description | BioLayout Express3D is a powerful tool for the visualization and analysis of network graphs. Network-based approaches are becoming increasingly popular for the analysis of complex systems of interaction and high dimensional data. Networks can be produced from a wide variety of relationships between entities. In biology this includes the interactions between individuals, disease transmission, sequence similarity, metabolic pathways, protein interactions, pathways, regulatory cascades, gene expression, clinical data. This tool represents the product of over 15 years research and development and uses a combination of high end 3D graphics, algorithms and user-friendly graphical interfaces to allow the user to explore and better analyse their data. |
Type Of Technology | Software |
Year Produced | 2007 |
Open Source License? | Yes |
Impact | The website currently receives hits from approx. 700 users a month from around the globe and is used 1500-2000 times a month. This tool has been used in analyses that have contributed to over 40 publications. |
URL | http://www.biolayout.org/ |
Title | Graphia Professional |
Description | This is a network analysis tool designed for the analysis of biological data. It is a commercial product produced by Kajeka Ltd a company founded on the IP and know how behind BioLayout Express3D. |
Type Of Technology | Webtool/Application |
Year Produced | 2015 |
Open Source License? | Yes |
Impact | This is the first product of Kajeka Ltd and sales of it will help support the company as it grows. |
URL | https://kajeka.com/graphia-professional/ |
Title | NGS graph generator |
Description | This online tool allows users to generate tanscsequence graphs and then v |
Type Of Technology | Webtool/Application |
Year Produced | 2014 |
Impact | Improved visualisation and detection of splice variants and DNA assemblies. |
URL | http://seq-graph.roslin.ed.ac.uk/ |
Company Name | Kajeka Ltd |
Description | The biological sciences generate vast amounts of data from numerous analytical platforms; the data is big, complex and multi-layered. Like all big data, its analysis and correct interpretation represent a significant challenge. Kajeka produces a data analysis platform for the visualization and analysis of numerical matrices and networks. Our network analysis tools provide a rapid analysis pipelines producing visually intuitive network representations of data structure, whatever the source, allowing you to make more effective, more efficient, data-driven decisions - quickly. Company offering network analysis tools for the analysis of primarily of omics data. The company's first product, Graphia Professional, is based on IP and know how behind BioLayout Express3D. The company are now (Feb 2019) about to release a new network analysis platform for the analysis of biological data called Graphia. |
Year Established | 2014 |
Impact | The company is still at an early stage in its development but is beginning to gain commercial traction and clients for the software. We have won one Scottish Enterprise grant and have submitted a second for the development of our next generation software. We also secured seed investment of £230k last year. We are collaborating with academic scientists who develop network analysis algorithms or who use network analysis in their work. We have a number of ongoing discussions with major pharmaceutical and platform providers. |
Website | http://www.kajeka.com |
Description | Easter Bush Campus Open Day 2018 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | The group ran two stands at this event, one on our work with honey bees including general interest items about beekeeping and bees, another was a display of the network analysis tools we have developed initially through BBSRC funding and more laterally as part of the spinout company Kajeka Ltd. Presenters Dr Mark Barnett and Prof Tom Freeman |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.ed.ac.uk/roslin/community-engagement/public-events/campus-open-day-2018 |
Description | Makers faire |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Presented BioLayout and how we are using the tool. Generated a lot on public interest. Good feedback on the day. |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.life.org.uk/whats-on/maker-faire-uk-2014#.VGOR9vmsVBm |
Description | School visits - Prestonfield primary school, Edinburgh |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Talk to P4 and P5 classes about biological research, especially around DNA as part of work week. Showed BioLayout and lots of questions asked by pupils. I was told by the teacher that after my talks some of children said they wanted to be scientists. |
Year(s) Of Engagement Activity | 2012,2013,2014 |