PhytoPath, an infrastructure for hundreds of plant pathogen genomes

Pathogen-mediated disease is a major cause of damage to crops, with considerable economic impact and consequences for food security. Global demand for food is rising because of population growth, increasing affluence and changing diets. In a typical cropping year in each field yield losses through infections caused by pathogenic microbes are rarely below 5% and are more typically in the range 10-15%. In recent years, new possibilities for the study (and ultimately control) of pathogens have opened up through the application of high-throughput technologies for determining the molecular nature of life. These include genome sequencing, which reveals the genetic code that determines inherited properties of cells - and extends to monitoring the varied cellular contents at different stages of life. PhytoPath is a resource designed to capture broad molecular information from plant pathogenic species, and combine it with descriptive information about the process of infection, including more specific molecular information, e.g. about the pathogen and host proteins that interact during infection and the phenotype of the interaction outcome. The former new knowledge on pathogen genomes, patterns of gene expression and potential interacting partner is housed using the Ensembl platform. Ensembl contains a comprehensive suite of software for the management and display of genome-scale data. The latter new phenotypic knowledge on experimentally verified genes required for the disease causing abilities of each pathogenic species is curated by members of the scientific community into the Pathogen Host Interactions (PHI-base) database. New interfaces (within and between) both these resources support the joint querying and visualisation of genomic and phenotypic data.

This is an application for a renewal of BBSRC funding (which commenced in late 2010). We propose expanding the resource, scaling it up to handle hundreds of fungal and oomycete phytopathogens (and associated data about population-wide polymorphisms), deploying new tools for community curation, and improving the facilities for comparative analysis from within the resource. For example, published RNA seq data will be used to predict new gene models and modify existing ones, but by deployment of a new tool for community-curation of gene models further expert revisions can be captured. Tools will be in place for the users to compare the reference genome of each species with the datasets arising from genome re-sequencing projects involving additional strains of a single species with different disease causing abilities, host genotype ranges and / or ability to produce different harmful mycotoxins/metabolites. A new curation focus on the phenotypic information will increase the details recorded about the molecular interactions between the repertoires of small effector proteins produced by pathogen and their initial targets within the crop hosts. New links will be provided allowing users to move freely between the genomes of both plant and pathogen. Also simple visualisation tools will be provide to display protein partnerships, and emerging sections of pathways and local network 'hubs'. We intend to capture molecular and phenotypic information on ~200 pathogenic species with a wide range of pathogenic lifestyles in cereal and non-cereal species. This will further increase the power of comparative analyses and evolutionary studies. The use of the existing pathogen associated microbe gene ontology (PAMGO) terms will gradually be introduced into the curation process. We will continue to engage with the large and active UK research community in this field, to find out their new requirements and to address their current needs through focussed workshops and University/Institute visits by specific PhytoPath team members. This resource will also serve the larger, global academic, industry and government based community increasingly concerned by the same scientific and societal problems.

We will maintain the resource (PhytoPath) for high throughput molecular biology data from important phytopathogens and pathogenic phenotypes based on the Ensembl software infrastructure for genome analysis and display and PHI-base, the leading resource describing phenotypes of pathogenic infection. Information will be stored in a relational database and made available through a number of public interfaces, including a genome browser, a query optimised data warehouse, and bulk data download. Services will be operated as an integrated part of the EBI's suite of public services, and integrated with other services offering access to genome-scale data from other species (e.g. the plant hosts of pathogen-mediated disease). Species and data will be selected for incorporation according to the current research priorities of the community. Data types of interest to PhytoPath include genome sequence, variation information, functional and regulatory assays, RNA-seq, transcriptomic and proteomic data. In this funding cycle, PhytoPath will include a new tool for the community-curation of existing gene models, to supplement the tool developed in the current funding round for the community curaton of host-pathogen interactions. PHI-base will be developed to include information on the primary host targets of pathogen effector(s) and their cellular location and provide a sequence search function, and the WikiPathways tool will be included within the user interface. We will develop methods for population-scale variation analysis, and comparative genomic analysis between pathogenic and related non-pathogenic species, and include the results in each release of the database. The activities of PhytoPath are overseen by a management board comprising key members of the UK phytopathogen research community.

The driving rationale for the project, as well as its greatest potential for societal impact, is in sustainably increasing the yields of crop plants, through assisting the development of strategies for pesticide development and plant breeding. Crucially, this depends on an understanding of gene function (effectors and their targets, and other downstream biological functions dependent on these), which determine the range of possible pesticide targets, the total genetic reservoir available to plant breeders, and possible side effects (in terms of the impact on plant growth, development and overall health). Massively reduced sequencing costs have led to a sharp (and continuing) increase in the number of sequenced phytopathogens. The power of such technologies, however, is critically limited by the quality of reference information (determined by individual scientific studies, and used to infer information about less well studied systems) and by the need to describe the role of given functional elements in the life of the organism. PhytoPath seeks to address this through providing a system for the management of genome-scale data interfaced with a repository of information about pathogenic phenotypes. Potential beneficiaries thus include not only academic researchers working in this field, but also companies developing pesticides, or attempting to breed new varieties of pathogen-resistant plants. More generally, farmers and the wider global population will benefit from improved strategies for disease control, although they are not expected to be among the direct users of the result.

The PIs at both institutions will engage with society, the media and policy makers to make the case for the importance of research into plant pathogens in the context of rising global concern about food and energy security, and of the potential benefits of genomics in addressing these concerns. But the main thrust of impact activities will be aimed at raising (academic and commercial) user awareness of the resource.

Impact will be achieved through attendance at relevant conferences, publication in the database issue of Nucleic Acids Research and other suitable journals, and through the use of our Scientific Advisory Board to gain feedback from critical members of the community about needs and use cases. Furthermore, we are directly seeking support for frequent visits to important BBSRC-funded UK laboratories for direct discussions with the staff employed there. Such visits will also involve offering informatics support for the submission of data to PhytoPath; and members of such laboratories will be additionally invited to visit EBI for short working visits where this will facilitate progress. We will additionally hold 2 training courses for members of the community, following on from the successful course already held in September 2012. Rothamsted Research (RRes) has an extremely strong track record in crop science; and in the study of plant pathogens; and is at the heart of a leading network of academic and commercial groups operating in these domains. Their BBSRC funded 20:20 wheat ISPG has the ambitious objective of raising potential wheat yields to 20 tonnes per hectare through 20 years of research. Work package 2 in 20:20 wheat - 'Protecting the yield potential of wheat' has several collaborative activities with both academic and / or industrial partners that will directly benefit from the growing data and species available in PhytoPath. The EBI is Europe's leading bioinformatics service centre and is ideally placed to exploit synergies between the activities of PhytoPath and other informatics activities; and is coordinating the ELIXIR project. The EBI also has a long established industry programme which helps guide future developments in accordance with commercial needs. Jointly, the two organisations are well placed to meet the needs of the user base in an efficient and sustainable manner.