We were deeply shocked and saddened to hear of the death of a real force for good in the world, Professor Richard Cotton. DNAdigest team would like to extend our most sincere condolences to his family and his colleagues who worked closely with him on the Human Variome Project. He was a great inspiration and huge encouragement to preserve our work for the common goal of sharing data.
Only a couple of weeks ago we interviewed Professor Cotton about his work on the Human Variome Project and his passing away so suddenly came as a shock to the whole DNAdigest team. Read below Richard Cotton’s answers to the questions that we asked him.
1. Please provide a short introduction in the Human Variome Project (HVP). What are the mission and aims of the organisation?
The Human Variome Project is a non-profit company registered in Australia. It has an international board and an international Scientific advisory committee. Chris Arnold is executive chairman and there are six scientific directors: Mike Watson (US), Garry Cutting (US), Johann den Dunnen (the Netherlands), Sir John Burn (UK), Finlay Macrae (Australia), and Ingrid Winship (Australia). It is inclusive and office bearers are elected.
Sharing of data in any topic is problematic. In the case of genetic diseases, data sharing could mean the difference between life and death. It is well known that much genetic data resides in hospital files without being shared. The mission of The Human Variome Project (HVP) is to reduce disease by sharing of data. It aims to facilitate data sharing in the area of genetic diseases caused by genetic variations across populations. Traditionally, and in the clinic, such variations have been called mutations.
2. How did HVP start? What were the driving forces?
The nucleus and concept of the Human Variome Project had its beginnings with the initiation of the journal Human Mutation in 1992. It was established because there was no other journal focusing on mutations and their documentation. The Journal encouraged submission into genetic repositories of all data that were published in it. Now, the Journal Human Mutation belongs to the top four journals in its subcategory indicating the importance of this topic in the field of genomics.
Besides the fact that there was a lack of focus on mutation data sharing, it was clear that there was neither software for collecting variant data nor policy of sharing or for systematic naming of variants. These were our driving forces to start this project. Consortium members first met in Minneapolis under the auspices of HUGO (human genome organisation) to form the HUGO Mutation Database Initiative in 1995.
To further the mission, aims, and sustainability of the movement, the consortium members decided to form the Human Genome Variation Society (HGVS) in 2000. The society still exists and is administered by the Human Variome Project. During the years of existence, consortium members developed and published a large number of recommendations regarding variant description, collection and sharing.
A further attempt to raise the profile and funding of the movement was launched in Melbourne in 2006. Representatives of WHO, UNESCO, OECD, HUGO, NCBI, Nature Genetics and Google were present together with high-profile international genetics researchers. The meeting voted to initiate the HVP and for it to be coordinated from Melbourne. The first planning meeting was in Spain in 2008 and subsequently every two years a meeting has been held at UNESCO headquarters in Paris. The next one is planned for June 2016.
3. What are the main activities of the Human Variome Project to date? How can one become a member of your organisation and contribute to your work?
These are the most high-profile achievements of the consortium members’:
- Creation of the HGVS nomenclature for mutations and variations in genes.
- Development of software for collection and curation of gene variations. One of them – LOVD – has been downloaded thousands of times and is capable of integrating whole genome analyses and spreading data to the various genes. An interesting recent feature is the ability to perform curation of variations in all genes across populations.
- Development of recommendations and standards for collecting and curating gene variations (details can be found on the HVP website).
- Initiation of an agreement with the Inherited Colon Cancer Society (INSIGHT) to be a model for collecting and curating gene variations. Clinical grade curation is performed by members of an international curation group via monthly phone calls.
- Initiation of the Malaysia node of HVP to be the model for all countries for collecting their own data and then sharing it within the country and with the rest of the world. The Malaysia node also represents the ASEAN regional node.
- Initiation and encouragement of further disease groups and databases including kidney diseases, mitochondrial diseases, globin diseases and breast cancer. The later has developed into the BRCA Challenge in association with the Global Alliance.
- Initiation of the Globin project in association with WHO (Global Globin 2020) as a model for other diseases in developing countries.
- Work with WHO on global genomics policy.
The Human Variome Project has over thousand members from 81 countries. 23 countries have signed to form country nodes. One can become a member by signing up on the website free of charge and can contribute by commenting on various documents, provide the ideas and especially by curating and collecting mutations. This latter activity is most critically needed.
4. How are you working with UNESCO and what advantages does this collaboration bring?
HVP has Associate NGO status with UNESCO. It supports an officer working within UNESCO. HVP works with UNESCO to make its member state delegations aware of the global efforts of HVP and highlights work being undertaken in these respective countries by local HVP collaborators. This is a valuable way of increasing support within countries for HVP activity and local initiatives.
UNESCO is also the host for the biannual HVP international conferences, which bring together global HVP participants to share information, ideas and to plan future activities. HVP is recognised by UNESCO as a key global body for advice on genetic and genomic heath and data sharing.
UNESCO, with HVP assistance, is currently developing a statement on ethics and standards for collection and sharing of genetic and genomic information. This is scheduled to be released at the bi-annual HVP meeting in Paris in June 2016.
5. Congratulations on the recently signed MoU (memorandum of understanding) with WHO! Could you please explain how this partnership will support the mission of HVP?
HVP is a global organisation, we want to see the world joined and working together on the challenges of translating developments in human genomics into improved health services. HVP’s mission is in agreement with that of WHO – we want to see open transparent variant data sharing that is both ethical and financially sustainable. We know from experience that low and middle income countries often get left behind when new techniques and diagnostics are developed. Currently, in genomics research activity, much of the investment of resources is concentrated in a few wealthy countries. Most of the discussions and debates about these challenges take place in North America, UK and EU. We aim to make sure that these discussions are opened up to health professionals among the whole world. We acknowledge their presence and we try to engage ourselves with them. Also WHO is the agency of health ministers and we know that they need to have the opportunity to engage in these discussions if the profile of genomics and health is to be a priority for health service delivery.
For example, our Global Globin 2020 Challenge seeks to apply the latest human genomics developments to well-known diseases such as sickle cell disease and thalassaemia that are very common in low and middle income countries. However, as a result of migration events, these conditions are spreading fast in parts of Europe, North America, and Australia. We are building a network of 20 countries around the world in order to develop capacity and address these forgotten diseases where they occur. We also want to make sure that health professionals working in these countries have a strong voice when we develop standards, procedures and codes of practice. We are looking for internationally harmonized and interconnected variant sharing and this cannot be achieved without the participation of many countries, not just rich countries. Those working in low resource countries have a lot to offer rich countries too, for example, how to do things cost-effectively, in low resources settings or with better utilization of community-based service delivery. Furthermore, we can foresee that there will be knowledge-based job opportunities in the future with demand for genomic based services in the coming years. We need to make sure that middle and low income countries build their own expertise and services locally as this will strengthen and enrich the field by ensuring a greater diversity of views.
6. How do you think the problem of limited data sharing should be addressed further?
Because clinicians and laboratory heads are very busy people it is very difficult for them to find time to submit their data to databases even though they use other people’s databases on a daily basis. The simplest way to overcome this problem is to make submission of genetic data to a database compulsory and/or make data submission part of quality control and/or licensing of laboratories. This compulsion is part of practice for cancer and infectious diseases in some countries.
7. How do you ensure data quality?
This is the most critical point as errors can mean life or death or removal or not of organs. Bioinformaticians are confident that their analyses may eventually safely predict the outcome of a particular variant. But many researchers believe the opposite. Thus, they believe that human curation of the ability of a particular variant to cause disease needs to be decided by a group of experts as per the INSIGHT example above. However, this is expensive and may be impractical. It could be that bioinformatics analysis at the protein level may be more accurate. Modifier genes may also make prediction difficult.
We thank Chris Arnold (chairman of the HVP) and Helen Robinson (WHO liaison officer) for their assistance in the preparation of this interview.