“Hepitopes: representing why I am an enthusiastic pioneer of the Wellcome Open Research platform.”

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Hepitopes’ is a new online resource, comprising a database of immune responses to Hepatitis B virus (HBV). We believe this will be an important resource for the HBV research community, with implications that range from characterising the basic science of virology and immunology, through to informing vaccine design and understanding clinical outcomes of infection. The database is designed as a live interactive resource that will evolve and develop over time, with improvements in the quality and content of the data, links to other tools and resources, and the potential to underpin scientific dialogue and new collaborations.

We coined the name as a concatenation of ‘hepatitis’ and ‘epitope’, the latter being a protein fragment that is presented by host HLA (human leukocyte antigen) molecules on the surface of an infected cell for recognition by CD8+ T cells.

What made us embark on this project? The crucial influence of the CD8+ T cell response is well documented in the control and clearance of viral infection, but there has been no previous systematic approach to assimilating a bank of HBV epitopes.  Meanwhile, there is increasing recognition of the multi-faceted problem posed by chronic HBV infection: the global burden of disease, potential pitfalls in vaccination and concerns about drug resistance.

An appealing solution for chronic HBV infection would be a therapeutic vaccination that boosts the components of the immune response most associated with natural control and clearance. For this reason, we set out to undertake a systematic literature review to identify all CD8+ T cell epitopes that have been reported in HBV. The project hinged crucially on IT input, and a close collaboration led to the development of an interactive open access online resource: http://www.expmedndm.ox.ac.uk/hepitopes.

Screenshots of the Hepitopes database

Screenshot of the Hepitopes database

 

However, the data set we have generated is influenced by various sources of bias and inconsistency. Our literature review may have overlooked important citations, and this now represents a fast-moving field in which new data will emerge quickly. For all of these reasons, a static cross-sectional literature review is of limited value, and a fundamental aspiration of this project right from the outset has been that it must grow and evolve over time. In simple terms, this means updating existing entries in the database. But the vision also extends to building a resource with more resolution, breadth and scope – adding insights about the biological impact of specific immune responses, developing data visualisation tools, and incorporating links to other online resources.

A publication in Wellcome Open Research supports this project in several important ways. It was particularly important to us to find a route to publication that did not involve long delays, as by the time we wrote the manuscript, the database was already live online. Reducing the delays inherent in traditional routes to publication makes the resource quickly accessible to a wide audience, delivering a real and tangible benefit to scientists and academics, and with the potential for accelerating output that is relevant to clinicians and patients.

Using this platform means that we can publish the database with sufficient details to provide context and make the work reproducible, and generate a PubMed indexed citation to make it identifiable, visible and accessible. In addition, we now have the flexibility to present and publish a project that – by its very nature – is perpetually unfinished. Indeed, its unfinishedness can now be acknowledged as a fundamental asset. Version controlled updates mean that our original work is never overwritten, but that the latest update always appears on top of the pile. Meanwhile, for any of us who might worry about metrics, we can assimilate citation counts, quantify the impact of our work, and demonstrate our output.

As well as developing the Hepitopes resource with our own new data and tools, we also invite contributions from a wider audience via an online contact portal. This highlights the significant potential for the project to initiate or enhance collaboration; in this instance, we hope it will allow us to develop discussions with groups who can offer overlapping or complementary data, resources and skills.

Finally, the platform allows us to access peer review, which will operate to provide important quality assurance, both to us and to others who use the resource. The open access approach to review offers all-round benefits: as authors you feel less vulnerable to a process that has not always been renowned for its meritocracy, while as a reviewer your valuable contribution becomes a recognised and citable part of an academic portfolio.

The success of the Hepitopes venture remains to be seen, but pursuing this route to publication gives us a launch pad that is creative, flexible and accessible without sacrificing scientific integrity.

 

Philippa Matthews is a Research Fellow in the Nuffield Department of Medicine at Oxford University where she is currently funded by a Wellcome Trust Intermediate Clinical Fellowship. Her research focuses on chronic hepatitis B infection, with a particular interest in populations in southern Africa. She is also an honorary consultant in Clinical Infection at Oxford University Hospitals NHS Foundation Trust. Her other interests include medical publishing, data visualisation and engaging school students through art and science.

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