BBMRI - biobanking for science
23-25 September 2010
Amsterdam, Netherlands

Organiser:

Draft Report

This report seeks to summarise the discussions that took place and the talking points that emerged during the “BBMRI – Biobanking for Science” meeting in in Novotel Hotel Amsterdam City, Amsterdam, NL, on September 23-25, 2010. The BBMRI Conference brought together researchers from academia and industry, research administrators, ethicists and lawyers from all over the world, mostly in Europe. The report has been produced from a combination of the meeting presentation and summaries of discussions during the conference. Presentations from plenary sessions and parallel sessions are all available on the BBMRI website (www.bbmri.eu).

Summary

BBMRI is a preparatory phase project funded by the 7th Framework Programme of the European Commission. Its mission is to prepare for the construction of a pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) for biomedical and biological research, building on existing infrastructures, resources and technologies, specifically complemented with innovative components and properly embedded into European ethical, legal and societal frameworks.

The conference "BBMRI -Biobanking for Science” collected together leading scientists in the field, young scientists, biobanking managers and practitioners to discussed the science and new approaches in cutting edge biobank research. The conference started on Thursday, September 23 with the fascinating opening words of Professor Gert-Jan van Ommen followed with a keynote address by Professor Daan Hommes from Leiden University Medical Center focusing on integration of electronic patient records (collected by iPhone), hospital care and biobanking. On the following days, two other high level key note speeches were presented. On the second day, Professor Thomas Hudson (President and Scientific Director of the Ontario Institute for Cancer Research) described new results in cancer research under a title “Translating cancer genomes into personalised health and disease management”. The conference ended with a keynote lecture by Professor David Cox from Pfizer highlighting the industrial perspective of biobanking.

The conference provided results and solutions from biobanking related research with inside views on the upcoming revolution in the developing and emerging technologies, including new generation sequencing, proteomics, metabolomics, systems biology, bioinformatics and data mining as well as data protection. These sessions were complemented by networking and knowledge transfer opportunities between members of industry, academic medical research and policy makers. More than 250 participants are attended the conference in Amsterdam to exchange information about the biological and genetic disease mechanisms, to improve the delineation of clinical phenotypes and to establishe biomarker spectra for disease prognosis and therapy. BBMRI Partners and Associated organisations had also an opportunity to present their biobanks in poster sessions.

Scientific Content

The programme was organized around three formal sessions (plenary sessions) and two parallel sessions. The following summary describes the scientific content and the discussions which took place in each scientific plenary session.

The first session focused on success stories (Clinical Outcomes) resulted on the biobanking related studies including better understanding of the biology underlying common and rare diseases. Heribert Schunkert summarised interesting results about the new understanding of the genetics of myocardial infarction (MI). The findings emerged from the application of novel high-throughput genome-wide approaches about the frequent risk-associated alleles acting independently of traditional risk factors. Based on the presentation, several chromosomal regions have been identified to affect the risk of MI. Although the number of risk alleles is growing rapidly, but several conclusions can already be made from the current findings. For example, essentially all Caucasians carry a variable number of risk alleles such that disease manifestation is affected to some extent by these inherited factors in basically all individuals. This means that a better understanding of underlying functional genomic mechanisms may offer novel opportunities to neutralise a broadly based genetic susceptibility for MI in a large proportion of the population. In parallel, the newly discovered genes open novel opportunities for disease prediction. In summary, modern MI genetics carries the promise to identify individuals at high risk and to improve prevention and therapy of this important disease.

Next, Tim Spector introduced the importance of twin registers in gene discovery based on the TwinsUK resource focusing the genetics of complex diseases, in particular age-related diseases, with a current main focus on the genetics of metabolic syndrome (obesity versus lifestyle) and how heritable cancer is, the pain sensibility, and ageing. The presentation enabled a range of unique approaches like metabolomics and epigenetic mechanisms to the understanding of genetic and environmental influences on disease and their interaction. Over than 4,000 phenotypes on twin dataset are available to collaborators (most phenotypes having been collected on at least 1,000 individuals). Professor Spector concluded that twin cohorts with multiple and novel phenotypes will continue to be rich sources of gene discovery because twins allow a unique design adjusting for genetic effects and testing for subtle structural differences.

In the end of the first session, Kari Stefansson (deCODE genetics) emphasised that isolated populations of people, which tend to be small, inbred populations, present a special challenge in population genetic research and related biobanking. Their homogeneity is of great value in research because genetic and environmental risk factors for complex traits can be more readily identified (e.g. type II diabetes, melanoma and some other cancer types, arterial fibrillation as well as schizophrenia). Further, the incidence of rare mutations is magnified in these populations, offering
opportunities to advance the knowledge of disease genetics. Greater harmonisation between studies on isolated populations would certainly be enriching, although it faces many of the same challenges seen in other types of biobanks. This underscores the value of being able to systematically analyse the impact of genetic risk factors across continental ancestries. Not only are these markers medically useful, they also tell us a bit about evolution and the spread of humanity across the globe, informed Kari Stefansson, deCODE’s Executive Chairman and President of Research.

The second session pointed out the key challenges about the data mining, analysis and protection with an ethical perspective too. Both Morris Swertz and Hakon Gubdjartsson illustrated an attractive vision for the future of IT-based “biobanking environment” that supports direct submission of data, seamless data integration, and holistic searching capabilities. Progress in life sciences research has produced enormous amounts of data but the production of suitable software infrastructure to manage and process these data has not been able to keep up. Part of the problem is that each research group has their own needs for biotechnologies, protocols and specific species on which research is done. Therefore, Swertz has devised a minimal programming language to quickly assemble these re-usable blocks of code, a so-called Domain Specific Language (DSL). The ‘domain’ in this case is biology. The ‘specific’ part means standardisation to make a number of operations easy. This may be adding a ‘sequence’ input box on the user interface or a database query for new types of biomolecular data. A bioinformatician setting up a system for a proteomics experiment for example only has to tell the system, using the DSL, what data types, data relations, screens and queries are needed for this type of experiment without having to ‘tinker under the hood’; how biological features translate into software code is too much detail due to the Swertz presentation.

Professor Klaus Kuhn presented a concept of BBMRI Catalogue which has been prepared of existing major population-based and clinical or disease-orientated biobanks in Europe. Based on questionnaires designed in collaboration with the Public Population Project in Genomics (P3G) information has been collected on type and quality of collected samples and data, standardisation of procedures, IT solutions as well as governance structure, funding, and legal and ethical issues. Data obtained from the survey can be accessed through a searchable catalogue at the BBMRI website (www.bbmri.eu).

Due to the very last minute cancellation (David Goldstain), Paul Burton kindly presented very interesting talk about the DataSHIELD developed to vast sample sizes (and there is often then no choice but to synthesise data across several studies) and to undertake an appropriate pooled analysis. When a pooled analysis is required, analytic efficiency and flexibility are often best served by combining the individual-level data from all sources and analysing them as a single large data set. Data aggregation through anonymous summary-statistics from harmonised individual-level
databases (DataSHIELD), provides a simple approach to analysing pooled data that circumvents this conflict. This is achieved via paralleled analysis and modern distributed computing and, in one key setting, takes advantage of the properties of the updating algorithm for generalised linear models (GLMs). As the study of the aetiological architecture of chronic diseases advances to encompass more complex causal pathways—e.g. to include the joint effects of genes, lifestyle and environment—sample size requirements will increase further and the analysis of pooled individual- level data will become ever more important. But ethical-legal constraints, including the wording of
consent forms and privacy legislation, often prohibit or discourage the sharing of individual-level data, particularly across national or other jurisdictional boundaries. Based on Paul Burton presentation this leads to a fundamental conflict in competing public goods: individual-level analysis is desirable from a scientific perspective, but is prevented by ethical-legal considerations that are entirely valid.

Lastly, Ruth Chadwick philosophised that in a few years’ time, it may be commonplace for our genetic ‘medicine response’ profiles to be consulted before selecting the appropriate treatment, but what does this imply for individual choice? The information coming from genomic studies and human population genetics could dramatically alter health care options. The identification of individual differences which affect our response to drugs, for example, is likely to make it possible for pharmaceutical companies to market, and physicians to prescribe, in the light of individual
genetic profiles, so tailoring medicine to maximise both the avoidance of side effects and favourable response to treatment. On the other hand issues of individual control of information may become more complicated, in both research and treatment. The prospects for predictive testing in genetics, however, have led to arguments for a right not to know genetic information, recognising that there are circumstances in which information may be a burden rather than a help, and that information may be misused. If drug prescribing follows this course, however, it may come to be regarded as negligent for doctors not to take genetic profiles into account, implying that we may all need to have our genetic medicine response profiles on a readily accessible database which means that too much for a right not to know.

The third session introduced a new developments and emerging technologies for the audience. The rapidly evolving field of metabolomics aims at a comprehensive measurement of ideally all endogenous metabolites in a cell or body fluid said Thomas Illig. It thereby provides a functional readout of the physiological state of the human body. Genetic variants that associate with changes in the homeostasis of key lipids, carbohydrates, or amino acids are not only expected to display much larger effect sizes due to their direct involvement in metabolite conversion modification, but should also provide access to the biochemical context of such variations, in particular when enzyme coding genes are concerned. To test this hypothesis, Illig et al., conducted the first GWA study with metabolomics based on the quantitative measurement of several metabolites in serum of the male participants of the KORA study. They found associations of frequent single nucleotide polymorphisms (SNPs) with considerable differences in the metabolic homeostasis of the human body, explaining up to 12% of the observed variance. They also identified some genetic variants in genes coding for several enzymes where the corresponding metabolic phenotype (metabotype)
clearly matches the biochemical pathways in which these enzymes are active. The results suggest that common genetic polymorphisms induce major differentiations in the metabolic make-up of the human population. This may lead to a novel approach to personalised health care based on a combination of genotyping and metabolic characterisation. These genetically determined metabotypes may subscribe the risk for a certain medical phenotype, the response to a given drug treatment, or the reaction to a nutritional intervention or environmental challenge.

During an interesting presentation by Ivo Gut, he introduced the next generation sequence (NGS) technologies enable high-throughput sequencing for applications including de novo sequencing and re-sequencing of (subsets of) genomic DNA, and whole transcriptome and transcript-tag sequencing. From the introduction of these new technologies, the developments have been very fast from the 1st generation to 4th generation sequencing. While the technologies are being improved further, and even next-next generation sequencing are more or less already available, pioneer researchers have started to successfully apply NGS to their research questions. However, because of the rapid developments, many scientists who are thinking about using NGS for their research have a need for information and sharing of (first) experiences.

Lastly, Ulf Landegren presented the ability to detect very low levels of expressed proteins which has enormous potential for early diagnostics and intervention at curable stages of disease. An extended range of targets such as interacting or post-translationally modified proteins can further improve the potential for diagnostics and patient stratification, and for monitoring response to treatment. These are critical building blocks for personalised treatment to manage disease. The past few decades have seen a remarkably improved understanding of the molecular basis of disease in general and of tumour formation and progression in particular. This accumulated knowledge creates opportunities to develop drugs that specifically target molecules or molecular complexes critical for survival and expansion of tumour cells. However, tumours are highly variable between patients, necessitating the development of diagnostic tools to individualise treatment through parallel analysis of sets of biomarkers.

Assessment of the results & impact of the event on the future direction of the field

The science of biobanking is rapidly changing because of the current revolution in the developing and emerging technologies, including new generation sequencing, proteomics, metabolomics, systems biology, bioinformatics and data mining as well as data protection. An impressive number of national and international initiatives have been funded to help biobanks and researchers collaborate in this cutting-edge science. Based on the presentations as well as discussions during the conference, an important result is the emergence of a new reservoir of knowledge, experience, and expertise that will benefit the biobanking community at large.

Conference participants also agreed to move forward in a joint and collaborative manner to address the challenges ahead. Biobanks have an increasingly important role to play in transferring knowledge to the hospitals and health systems in general as well as to the public in an effort to stem increasing healthcare costs. As meeting participants observed that the sustainability of a biobank may depend on its ability to become embedded in the health care infrastructure, to rationalise incentives along the continuum from data collection to data sharing. The content of the IT-sessions clearly reflected that international biobanking has moved beyond the initial stages of laying the groundwork to a highly interactive and multidisciplinary science. Analysis facilities are needed to handle the growing complexity surrounding the phenotypic data, the analytic strategies, and the larger quantities of data being generated. Substantial infrastructure and greater integration of new technologies from mathematical modeling to database technology is needed to achieve high-quality statistical analyses in a harmonised manner.

In continuation with discussions at the previous biobanking related meetings, the speakers and participants felt that BBMRI (and biobanking in general) should place strong emphasis on the collection of new data from diagnostic and treatment outcomes. This is a main area where biobanking may serve the public and governments to make better, more informed choices. Combination of genetic and biomarker profiling will allow the implementation of specific, advanced preventive health care, otherwise too costly to be offered to large, poorly defined disease categories. While many outcome studies are in private hands, there is increasing willingness to share precompetitive or potentially declassified information (eg. due to strategic repositioning). Moreover, the increased demand for outcome measures by regulatory authorities will also assist in moving these data into the public domain. In the future this could be handled through the Public- Private interactions using the Expert Centre model introduced by BBMRI and by involving more pharmacologically-oriented biobanks.

David Cox also emphasised in his presentation that in the future BBMRI should strive to share existing knowledge to generate the new knowledge (= translating new knowledge) with
-new prospective biobanks
-scientific collaboration through Expert Centres
-more clinical biobanks collecting treatment outcomes.
If successful, this will be a new way towards translational medicine by industry and academia working together in Expert Centres focusing on prospective biobanking.

The main message from ELSI-ERIC and beyond session was an interesting preliminary result of a comparative study on public perceptions of European collaboration and biobanks with conclusion that European citizens are, by and large supporting transnational cooperation and remain sceptical about commercialisation. In addition, the ongoing work of BBMRI’s Data Protection Group that was set up to achieve a pan-European solution for cross-border data protection. The Data Protection Group bases its work on the common minimum standards as laid down in Directive 96/46/EC. Furthermore, the Data Protection Group puts special emphasis on testing data flow within BBMRI. The results shall feed into the implementation of BBMRI’s federated information management system.

In conclusions, the conference highly helped to elevate the dialogue by encouraging critical thinking about opportunities, challenges, and next steps in the field of the biobanking. It is crucial that the biobanking community continue to interact as science advances and to share insights, continually raise the quality of biobanking science, question conventional thinking, and speak as one European as well as a global voice when it counts.