This interview was conducted by Gustav Ceder on behalf of Biobanking.com.
Aarno Palotie is Scientific Director of FinnGen and director of the Human Genomics Program at the Institute for Molecular Medicine Finland in Helsinki. He is also a faculty member at the Center for Human Genome Research at the Massachusetts General Hospital in Boston, and an associate member at the Broad Institute of MIT and Harvard.
FinnGen, launched in 2017, is a large public-private partnership aiming to collect and analyze genome and health data from 500,000 Finnish biobank participants. FinnGen provides novel medically and therapeutically relevant insights but also a world-class resource that can be applied for future studies. FinnGen brings together Finnish universities, hospitals and hospital districts, biobanks, international pharmaceutical companies and hundreds of thousands of Finns.
FinnGen is funded by Business Finland and thirteen international pharmaceutical companies including Abbvie, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, a member of the Roche Group, GlaxoSmithKline (GSK), Janssen, Maze Therapeutics, MSD (Merck & Co., Inc), Novartis, Pfizer and Sanofi.
In addition to genetics, Finngen recently started to perform multiomic analyses on subsets of samples using a variety of multiomic platforms, for example the metabolomics platform by Metabolon and the proteomics platform by Olink Proteomics.
Dr. Palotie, what is the significance of multiomics in biobank research?
There are specific gene variants which we know are associated with a disease and that are also enriched in Finland due to the genetic background. We want to answer the question, what are the metabolomic, proteomic and transcriptomic consequences of these variants, both before the disease and after disease? Can proteomics teach us something about the mechanism of disease progression and disease trajectory?
Whether they are case control studies or biobank studies, these studies have guided us towards gene loci (note: a locus is the specific physical location of a gene or other DNA sequence on a chromosome, like a genetic street address).
The question is, how do you move from the gene loci to biological understanding?
One approach is functional studies, and among these functional studies, multiomics is one avenue.
Since multiomics are new methods, researchers like to explore what type of additional information about the consequences of genetic variation that they can provide us. When time moves forward, we will start to understand what scientific questions these new methods can help us to answer, and at FinnGen we are particularly interested in using omics data to understand the biological consequences of enriched variants in the Finnish population.
With metabolomics, we are already in the face that that we have large datasets available, whether they are nuclear magnetic resonance spectroscopy or mass spectrometry based. UK Biobank has provided a good amount of information that researchers can explore and understand what value they can bring.
Proteomics is now the next omics where the large-scale exploration is ongoing, and again UK Biobank is the poster boy there. During the next year or two, there will be an opportunity to really analyze it and to understand what proteomics gives us.
The next phase is, how can we use proteomics or metabolomics to ask more specific questions? The need to do a holistic approach is maybe slightly diminished because there are already big data sets. However, one of the next steps is to analyze serial samples from different stages of disease trajectories to understand the metabolic and biological events in disease progression.
At FinnGen, we don’t quite have the financial opportunity to do 500,000 samples, besides, there is a lot of preanalytical data that needs to be in place before it makes sense. We are planning to do around 10,000 samples and about 2,000 samples will be profiled using single cell transcriptomics and ATAC sequencing.
How do you expect proteomics to develop in the clinical arena?
As a medical doctor and clinical chemist, I am used to the idea that every test needs to be validated and its clinical impact needs to be understood, and this is typically a very long path.
Having a broad set of thousands of measurements is a new ball game for a clinician. How do you interpret the omics background of a patient? How do you translate that data into clinical actionable knowledge?
We are still in very early days. More research needs to be done before we really understand what the proteomic profile could tell us about the health of an individual.
Is there a divide between research and the clinic?
Absolutely, has this not always been the case when new technology has been introduced?
Even when we look at genetics, how do we create more healthcare interventions based on our quite mature understanding of genetics that has been developing during the last 20 years?
One positive thing that is benefitting development is AI and big data. People are starting to get used to big data sources. The notion that a large data set can be used in decision making if analyzed in the right way, is getting established. There is a big paradigm shift in large scale data usage that not only concerns proteomics or metabolomics, and this paradigm shift will help to bridge the gap between research and clinical implementation.
Can you list the three most important trends in biobanking right now?
The first, and most important trend, is ethnic diversity. Most studies have been done on populations of European descent. We need a much larger understanding of the human population. The second trend is to combine omics and other functional data with genetic data, in large enough data sets. The third trend is understanding the longitudinal nature of human life and human disease, in order to understand how genetic variants are associated with disease risk and progression.
What are some of the key parameters of the success of FinnGen?
There are particular strengths of the Finnish health ecosystem that are unique in an international context, such as our national health registries, enabling legislation, and a strong national biobank network. In addition to national collaboration, we have an exceptionally broad international collaboration, with complementary strengths.
When you work with researchers for a long time you build trust and community through face to face meetings. Zoom is great, but more so when you already know the people. Many of the researchers who are now in international pharma, were our previous colleagues from Wellcome Sanger Institute, Broad Institute, UCLA etc. I also have close discussion and collaboration with biobanks in Japan, Taiwan, Singapore etc.