Wormbase-ParaSite

Lead Research Organisation: EMBL - European Bioinformatics Institute
Department Name: Ensembl Genomes

Abstract

Flatworms and roundworms are diverse groups of organisms and include those responsible for serious human, veterinary and plant diseases. Their global impact is hard to measure but annual human morbidity is estimated to be equivalent to at least 50 million productive years of life (c.f. 85M for HIV/AIDS), and agricultural losses from plant parasitic nematodes can be measured in hundreds of millions of dollars. Despite their impact on human health, a recent report highlighted that parasitic helminths attract only $77M per annum in research expenditure (cf. $1.1billion for HIV/AIDS). Due to the wide range of pathology caused in various host species, no single model species can capture the range of disease-causing mechanisms involved. Parasitologists are therefore inherently interested in making comparisons between many different species. Access to genomic-scale datasets has revolutionized molecular and cell biological studies of protozoan pathogens, advancing basic and applied research, but this is only now starting to happen for parasitic worms. Major sequencing programmes are now underway and large scale functional genomics datasets are beginning to emerge (e.g. RNA-Seq is becoming commonplace). Studies of genomic variation in multiple isolates, to address clinical, epidemiological or applied agricultural questions, are the obvious next steps.

While the emergence of new genome-scale datasets is immensely exciting, genomes are often produced in a relatively poor states of assembly and annotation compared to existing reference genomes. Moreover, the prevailing paradigm for organising genomic information (essentially, the genome browser and the underlying data models that support this) are relatively poorly fitted to the exploration of hundreds of highly fragmented genomes with limited functional characterisation. In this application, we propose the creation of a new resource to organise, classify and allow the exploration hundreds of worm genomes, facilitating the exploitation of sequence-based data for understanding and ultimately controlling worm-induced pathology.
The propose resource will be called WormBase-ParaSite, and will be strategically aligned with WormBase (the main resource for the model nematode Caenorhadbitis elegans). Specifically the resource will provide:

(a) Gene structures and functional annotation for unannotated worm genomes.
(b) Comparative genomic analysis, visualisation and querying.
(c) Methods for exploration and data mining the complete data set, through an intuitive query-building interface accessible to research scientists.
(d) A platform for the visualisation of the results of high-throughput sequencing experiments in the context of other annotation that enables functional genomics and variation studies.
(e) An infrastructure for accepting and integrating functional annotation submitted from the community engaged in worm research.

The project will complement the existing scope (and leverage the existing content) of WormBase, which has supplied biologists working on the model worm Caenorhabditis elegans with an invaluable information resource since the genome of this species was one of the first to be deciphered. It will provide additional capacity and tools for the handling of a massively increased quantity of genomes, with a clear focus on the information that is most relevant to parasitologists. The resource will also provide a home for data from the flatworms, such as flukes and tapeworms, which are outside the scope of WormBase.

Technical Summary

WormBase-ParaSite will be a new database and user interfaces focused on parasitic helminths, i.e. roundworms and flatworms. Large numbers of these genomes are currently being sequenced and the new resource will solve the problem of badly-organised and inconsistently annotated genomes, which if unaddressed, will make these valuable data hard for researchers to utilise effectively. Over a period of 3 years, we propose to structurally and functionally annotate at least 200 genomes using well-documented, state-of-the-art approaches (e.g. use of Augustus/Maker, RFAM, InterPro etc.), and to perform comparative analyses based on selective pairwise and multiple DNA alignment, HMM clustering of protein sequences, and evolutionary analysis of protein families. We will develop new data mining tools (based on established data warehousing infrastructure such as BioMart or InterMine) to allow users to efficiently extract information from the database, offering queries relating to e.g. genetic variation, gene content, taxonomic distribution etc. The user interface will be based on the Ensembl platform and support the ability to compare reference and other data stored in the resource to user-generated data stored in standard file formats (e.g. BAM for alignments, VCF for variants, etc.) via easy-to-use upload/visualisation tools . Apart from this interactive interface, the proposed resource will also allow programmatic access to the data. Frequent data releases will ensure the prompt availability of data and analysis results to the community. To allow ongoing improvement of the annotation, we will deploy a community curation tool, while we will also work closely with WormBase, the database for the model nematode C. elegans, which is expected to provide an eventual home for some of the genomes of highest interest. Finally, we will run an open workshop aimed at training scientists in efficiently using the database resource and its visualisation and analysis tools.

Planned Impact

Parasitic helminths are studied with the aim of killing or controlling them. The proposed resource will significantly facilitate the exploitation and application of sequence-based data towards this aim. For pathogens with smaller and simpler genomes such as viruses and bacteria, genomic insights are already being translated into tangible benefits for medicine such as the ability to track pathogen transmission and the monitoring of drug resistance. Yet it is clear that the application of genomic science towards medical, veterinary and agricultural improvements is still in its infancy, and that many more and bigger benefits will be realized in the long term.

In analogy, sequencing-based research is expected to deliver significant benefits in the fight against the diverse helminthiases afflicting humans, animals, and plants. Downstream beneficiaries will first and foremost be people directly suffering from helminth infections, which includes about 2 billion people infected with soil-transmitted helminths alone (WHO 2012). Advances in drug treatment, transmission reduction or vaccination could improve the lives of many people who may otherwise suffer from serious gastrointestinal disease, stunted growth and mental development, malnutrition and fatigue, disfigurement, blindness, or liver and bladder pathologies. Although some effective anthelminthics exist, the available arsenal of drugs is limited and makes the development and spread of drug resistance - especially with mass drug administration being a predominant tool for helminthiasis control in developing countries - a real danger. Furthermore, large-scale improvements in the treatment and control of helminthiases are likely to bring huge socio-economic benefits to some of the least developed countries.

In addition to the direct health improvements from a reduction in helminth infections, people in endemic areas could also benefit indirectly e.g. by an improved response to vaccinations, by reduced transmission or by an improved disease outcome for other diseases such as tuberculosis, malaria, and HIV/AIDS, as co-infections with helminths have been shown to have potentially adverse effects (see Elliott and Yazdanbakhsh, 2012, and other articles in the same issue of this journal for recent reviews).

In the UK, one major impact of helminth-related diseases is on agricultural production, especially in the potato and in the sheep and goat farming industries. Improved interventions and control measures against helminths such as Globodera, Teladorsagia, and Haemonchus spp. could therefore greatly benefit UK farmers and related agricultural and pharmaceutical industries. Globally, species of the genus Heterodera are significant nematode pests of various agricultural plants including cereals and soybean. The proposed resource will therefore fit squarely within the BBSRC's strategic research priority of 'Food security' and contribute to the areas of 'Crop science, 'Animal health', and 'Livestock production'. In addition, novel or improved helminth interventions could benefit pet owners and their companion animals and could help reduce the environmental impact of the large-scale application of nematicides for crop production. On the other hand, the proposed resource could ultimately also contribute to an improved use of beneficial nematodes as e.g. entomopathogenic nematodes to fight pine weevils.

Looking further into the future, a thorough understanding of helminths and their interactions with the human immune system may lead to fundamental new insights that will allow a much more sophisticated manipulation of the human immune system for medical purposes. Similarly, scientists are just beginning to uncover the complex interactions between the gut microflora (i.e. bacteria), the macrofauna (i.e. helminths), and human immunity. Together, such knowledge may ultimately be exploited for and benefit the effective treatment of allergies and other (autoimmune) diseases.

Publications

10 25 50
publication icon
Lee RYN (2018) WormBase 2017: molting into a new stage. in Nucleic acids research

publication icon
Howe KL (2016) WormBase 2016: expanding to enable helminth genomic research. in Nucleic acids research

publication icon
Howe KL (2017) WormBase ParaSite - a comprehensive resource for helminth genomics. in Molecular and biochemical parasitology

 
Description We have developed WormBase Parasite (http://parasite.wormbase.org), a new resource currently providing access to 134 genomes from 114 nematode and flatworm species. Data available includes genome assemblies, annotations, comparative genomics, and functional analysis. We have developed a new extension to the BioMart data mining framework to support querying over multiple species, allowing users to select data from any selected portion of the taxonomic tree. We have built and maintained links with WormBase (the reference database for the model nematode C. elegans) and Ensembl. We have made 9 releases of the resource and have presented the resource (with interactive training workshops) at 3 centres of helminth research in the UK, in addition to at national and international conferences.
Exploitation Route For those studying parasite-mediated pathologies, ParaSite provides an organised way to efficiently access the data; and information about similarities and differences between genes, and species, that will potentially provide the information needed to develop new strategies for control and treatment. A variety of interfaces (interactive and programmatic) are provided to facilitate data access.
Sectors Agriculture, Food and Drink,Chemicals,Pharmaceuticals and Medical Biotechnology

URL http://parasite.wormbase.org
 
Description Bioinformatics and Biological Resources Fund
Amount £600,000 (GBP)
Funding ID BB/PO24602/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2017 
End 12/2020
 
Title Multi-species BioMart 
Description The BioMart data warehousing framework was extended to directly support simultaneous query over multiple data sets, and the resulting software was deployed as part of the WormBase ParaSite website. 
Type Of Technology Webtool/Application 
Year Produced 2015 
Impact The extended BioMart allows for more powerful querying to identify sets of genes over many species matching common search parameters. WormBase ParaSite had a total of 19,247 unique visitors (measured by IP address) in 2015. 
 
Description Annual workshop at the British Society of Parasitology spring meeting 2016 and 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Practical workshop demonstrating common use-cases for WormBase ParaSite tools
Year(s) Of Engagement Activity 2016,2017
 
Description Half day hands-on workshop giving introduction to WormBase ParaSite, Glasgow, 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact A workshop comprising talks and hands-on training was presented to a group of interested researchers.
Year(s) Of Engagement Activity 2016
 
Description Presentation and Workshop at "Molecular and Cellular Biology of Helminth Parasites IX" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Awareness raised of the resource and of the projects generating the data it contains, and of its potential to impact research into helminth-mediated disease.
Year(s) Of Engagement Activity 2015
URL http://hydra.bio.ed.ac.uk/hydra/sites/sbsweb2.bio.ed.ac.uk.hydra/files/editor/HydraBooklet-website.p...
 
Description Presentation and workshop on "WormBase ParaSite: on-going development of an open access helminth genomics resource" to the conference on "Molecular and Cellular Biology of Helminth Parasites", 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Workshop/talk giving brief introduction, then focussing on new features in WormBase ParaSite
Year(s) Of Engagement Activity 2016
URL http://hydra.bio.ed.ac.uk/Hydra,%20Greece,%2031%20August-5%20September%202015
 
Description Presentation to International C. elegans meeting. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk on "Introduction to WormBase ParaSite tools"
Year(s) Of Engagement Activity 2015
 
Description Presentation to conference on Molecular and Cellular Biology of Helminth Parasites, 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation on "WormBase ParaSite - an online resource for helminth genomics" to an audience of helminth researchers.
Year(s) Of Engagement Activity 2015
URL http://hydra.bio.ed.ac.uk/Hydra,%20Greece,%2031%20August-5%20September%202015
 
Description WormBase ParaSite workshop - Aberwystwyth 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact A full-day workshop comprising talks and hands-on training was presented to a group of interested researchers.
Year(s) Of Engagement Activity 2016
 
Description WormBase ParaSite workshop - Edinburgh 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact A workshop comprising talks and hands-on training was presented to a group of interested researchers.
Year(s) Of Engagement Activity 2016
 
Description WormBase ParaSite workshop at British Society for Parisitology Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Introduction to key features and use cases of WormBase ParaSite.
Year(s) Of Engagement Activity 2016
URL https://www.myeventflo.com/event.asp?evID=1897
 
Description practical workshop at Molecular Helminthology: An Integrated Approach 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Practical workshop presented to an audience of scientists
Year(s) Of Engagement Activity 2017
URL https://www.elsevier.com/events/conferences/molecular-helminthology-an-integrated-approach