Share or be shared. During the last two weeks, the RES consortium has approved a new data sharing policy that will allow us to work with increased transparency and accountability within our upcoming projects. This new data sharing policy is a consequent extension of the previous protocols we had in earlier consortia – with one major difference. This time, it’s in writing. While we are getting ready to tackle the large dataset on epileptic encephalopathies released by the Sanger Institute, we took a moment to talk about how things should be running.

Building mutual trust. Many of the projects in epilepsy genetics that I have been involved with have been running smoothly without any kind of formal agreement between the research groups involved. While this may seem to be a sign of weakness given the complexity and mutual dependencies of modern genomic research, it is the opposite. Working within consortia like EPICURE or EuroEPINOMICS the lack of material transfer agreements, publication moratoria or conflict of interest statements has been a sign of mutual trust. We simply didn’t need this.

La Defense in Paris from up high (my hotel room at ESHG). I didn’t even know that Paris had buildings that had a 28th floor. When drafting the rules for the EuroEPINOMICS-RES consortium, keeping a bird’s eye view to look at the larger picture is one of our tasks.

So what is so different this time around? First, we are dealing with the largest dataset that we have handled so far. While the number of 100 trios with epileptic encephalopathies might not sound as overwhelming as it might have a year ago, this is the largest dataset on rare epilepsies generated in Europe so far. And we need rules to deal with this. Secondly, trio exome sequencing and the identification of de novo mutations puts us in a difficult situation. In contrast to the more “anonymous” data generated by genome-wide assocation studies, trio exome sequencing produces result that applies to a single patient. Therefore, in order to keep the balance between the contributing clinicians, researchers involved in the analysis and the “larger picture”, we needed a set of rules that we can play by. Third, times are changing rapidly. When we started the RES project, we had the strong belief that the majority of patients with epileptic encephalopathies can be solved. However, while there is good evidence that trio exome sequencing can explain a larger fraction of genetic morbidity in neurodevelopmental disorders than all other technologies combined, we may possibly produce an even larger number of variants of unknown significance. For example, a single de novo mutation in a new, promising gene might be a false positive finding. Such a finding only makes sense if it is also found in unrelated patients with the same phenotype or is shown to be pathogenic in other ways.

The umbrella. Our new data sharing agreement has quickly gained a nickname – the “umbrella”. Within the umbrella, data will be shared freely between partners who agree to certain principles. These principles include statements regarding conflict of interest, a “no surprise policy”, and an emerging publication strategy that should prevent inequality due to different time points of data access and an obligation to contribute. In addition, the partners agree to share information with outside groups in a structured way supervised by a governance board. Having such a solid, agreed upon structure is crucial to involve additional groups, which is one of the aims of the consortium. With this set of rules, we aim to increase the mutual trust between the currently 20 groups contributing to the RES consortium. The RES consortium is heterogeneous with respect to the expertise and focus of the contributing partners, ranging from genomic groups to purely clinical groups. We believe that this heterogeneity is representative of the colorful landscape of European epileptology and has the unique potential to translate our data into meaningful findings that will help us understand epilepsy a bit better. We have all worked hard to get this agreement into place and I am very proud and happy to be part of this consortium.

Sustainability for the years to come. There is another aspect of the data sharing agreement. We are basically bracing for a period of austerity. There is no major grant for epilepsy genetics in Europe in sight, and I don’t think that I am overly pessimistic to suspect that such a grant will never materialize. There is no funding mechanism available to give us the possibility for large-scale sequencing projects, centralized biobanks and feature-rich phenotype databases. And this is a feeling that is slowly sinking in. Within the RES consortium, one possibility to prepare for the “day after tomorrow” is to be proactive and explore alternative ways of funding large-scale projects. Within our exome fund initiative, we have already pioneered a grass-roots approach to contribute to the current sequencing batch through multiple small contributions by the research groups involved. Such a model could help us sustain the RES infrastructure for the years to come and provide some capacity for future large-scale sequencing projects. We hope that this effort can be supplemented by additional, smaller grants to the individual RES members. Having built trust with a transparent, accountable data sharing procedure will convince the contributing groups that building a community resource for the genetics of rare epilepsy syndromes will be worthwhile.

Rules to be made. We have only begun to formalize our rules within RES. Again, as there is basic trust between the research groups involved, there wasn’t much need for this in the future. However, these rules are now needed to build a consortium for the years to come. The RES consortium will need to decide on a transparent governance structure, devise rules to communicate and collaborate with other consortia, and define clear criteria for membership. The current RES partners are from 11 different European countries with different backgrounds. This makes the discussion for rules within RES a challenging and exciting task.

Ingo Helbig

Child Neurology Fellow and epilepsy genetics researcher at the Children’s Hospital of Philadelphia (CHOP), USA and Department of Neuropediatrics, Kiel, Germany