Despite limits in size and investment, biobanks such as Estonia’s are providing deeper understanding of the factors influencing public health and diseases, explains PacBio’s Neil Ward.
Health research is undergoing two seemingly opposite shifts at the same time. On one hand, the focus is zooming in to the individual. Medicine is becoming more personalised, powered by genomics. By focusing on an individual’s genetic profile, tailored decisions can be made around the prevention, diagnosis and treatment of disease for that particular person.
On the other hand, the focus is zooming out to wider populational studies. By analysing large-scale datasets, decisions can be made about the health of entire populations, including how to allocate healthcare resources, where to focus screening programmes, and how to decrease the incidence and severity of diseases.
The results so far are promising. For example, the Estonian biobank identified polygenic risk scores for breast cancer for hundreds of patients in a study
Both approaches reap incredible results individually – but when combined, the potential is extraordinary. This combination of personalised and population research is exactly what biobanks support. Now, researchers around the world are closely watching a bold initiative underway in Estonia that strives to see how genomic insights can be applied to benefit the lives of millions.
Banking on better health
Biobanks contain large amounts of individual biological samples gathered for research purposes. Since genetic material is gathered at scale, biobanks create opportunities to gain a deeper understanding of the genetic factors that influence health and disease among populations. The samples also hold a wealth of personalised genetic information that can be used to improve health outcomes for individuals.
The benefits of biobanks are well recognised, and globally there is support to establish them at a population-wide level [1]. However, many biobanks remain limited in size and investment [2]. There are relatively few organised at a national level, and most do not include enough of the population to enable meaningful insights at scale, particularly when considering the heterogeneity of diverse populations. The UK Biobank is heralded as a leading example and includes data from an impressive 500,000 participants [3] – but this still only represents 0.7% of the population.
Case study: Estonia
The Estonian biobank may be smaller than the UK one, with around 212,000 samples, but this represents a fifth (20%) of Estonia’s population. And it reflects age, sex and geographical distribution [4]. This huge data collection has been made possible by Estonia’s 2000 Human Genes Research Act, which enabled the establishment of the national biobank to organise genetic research [5]. That far-sighted decision over 20 years ago is already reaping rewards, and providing a path for the rest of the world to follow.
Unlike other biobanks, Estonia’s biobank is transparent to participants, sharing genetic results directly with volunteers. The newly launched participant portal allows people to read about their health-related genetic risks, drug metabolism, genetic origin and more [6]. Any patients deemed at high risk due to their genetics are recalled for further investigation. This approach makes the biobank a pioneer for a truly genetics-first approach to healthcare other nations could learn from. The results so far are promising. For example, the Estonian biobank identified polygenic risk scores for breast cancer for hundreds of patients in a study. Those at high risk were referred to an oncologist for mammography screening and offered new treatment plans [7]. This success led to the rollout of a national polygenic screening programme for breast cancer and a reduction in the age threshold for regular calls for mammographic screening for those with high risk. Since catching cancer early is critical, lowering the screening age could greatly improve the prognosis for future cancer patients.
The next level
The Estonian biobank recently received extra funding from the European Commission, matched by the Estonian government, for a new project powered by a more advanced type of genomic technology – long-read sequencing. Long-reads enable the sequencing of much longer DNA fragments than traditional sequencing, greatly simplifying the interpretation of the data. The depth and accuracy of long-reads also enables researchers to assess more complex parts of the human genome associated with conditions such as cardiovascular diseases and cancer.
Additionally, long-read sequencing will allow the Estonian biobank to analyse the epigenome. This collection of chemicals marks the genome in a way that tells it what to do and where and when to do it.
Certain epigenetic mark ers act as early indicators of disease, for example predicting cancer before solid tumours grow. By recalling patients to collect new samples, the Estonian biobank could be able to chart changes in an individual’s epigenetics, and their disease progression.
One other key area the biobank is exploring is genes related to drug response. This research – known as pharmacogenomics – will pave the way for personalised prescriptions that are safer and more effective for patients. The biobank holds a wealth of information about what drugs have been prescribed to people, and any adverse drug reactions. The hope is that by combining drug history and long-read data, the biobank will determine what genetic changes, in the complex genes that control drug metabolism, are responsible for those outcomes.
A new benchmark
The Estonian National Biobank exemplifies how integrating both personalised medicine and populational health genomics uncovers insights to improve the health of its citizens. It is not just its unprecedented reach within the country that makes the biobank so pioneering – but its proactive and transparent engagement with participants, and its embrace of cuttingedge technology such as long-read sequencing.
With this approach, the Estonian Biobank has become more than a research centre. It has enabled Estonia to carve a path towards precision medicine at scale that will unlock better outcomes for patients. Now, it’s time for health systems around the world to follow its lead.
References:
1 Armanasco AA, Lee A, Liu B, McIndoe L, McNamara M. Unlocking the power of population health cohort studies with biobanking in Australia. Public Health Res Pract. 2022 Dec 13;32(4):32012201. doi: 10.17061/phrp32012201. PMID: 36509684
2 Biobanks and the Public. Governing Biomedical Research Resources in Europe. A Report from the BBMRI Project. 2013. Available at: https://www.bbmri-eric.eu/wp-content/uploads/BBMRIBiobanks-and-the-Public.pdf
3 UK Biobank. About our data. Available at: https://www.ukbiobank.ac.uk/enable-yourresearch/about-our-data
4 ERR. Estonian Biobank launches one-of-a-kind online biobank portal. 2024. Available at: https://news.err.ee/1609368149/estonianbiobank-launches-one-of-akind-online-biobank-portal
5 Front Line Genomics. World of Genomics: Estonia. 2024. Available at: https:// frontlinegenomics.com/worldof-genomics-estonia/
6 ERR. Estonian Biobank launches one-of-a-kind online biobank portal. 2024. Available at: https://news.err.ee/1609368149/estonianbiobank-launches-one-of-akind-online-biobank-portal
7 The Pathologist. Biobank Boost. Estonian Biobank paves the way for the future of personalised health care at a national level. 2024. Available at: https://thepathologist.com/diagnostics/biobank-boost
Neil Ward is VP of PacBio EMEA and has been involved in several significant biobank projects including Genomics England’s 100,000 Genome Project, the Estonian Genome Project, and the whole genome sequencing of the 500,000 UK Biobank samples
