Functional genomics, or the effect of DNA sequence variants on quantitative trait variability and disease risk expression in the population, has made EGC one of the most studied biobanks in the world, with EGC researchers participating in the work of numerous international consortiums and contributed to the discovery of more than 35,000 (65%) of the genetic variants associated with complex characteristics.
As new fields of research, EGC has successfully launched systems biology, microbiome and pharmacogenetics, bringing to Estonia experts with an international background. The research at EGC directly supports the activities of the Estonian National Personalized Medicine Program, both with the development of polygenic risk scores and with the improvement of genotyping chip data. As new directions we see multi-level analysis of the health trajectories of gene donors, analysis of molecular profiles at DNA, RNA, proteins, metabolites and cellular traits level, and hypothesis-free data mining using machine learning and AI techniques.
The head of the Estonian Genome Center Science Center is Vice Director, Professor of Epi- and Pharmacogenomics Dr. Lili Milani (lili.milani [ät] ut.ee).
Despite recent advances in pharmacogenomic research, interindividual variability in drug metabolism and sensitivity for drug toxicity persists as a major problem for drug treatment. Recent research has highlighted the large extent of rare variant in genes with importance for drug metabolism. The aim of this work is to discover and investigate the effect of common and rare genetic variants related to suboptimal drug metabolism and adverse drug reactions (ADRs) in the Estonian and other European populations. This will be achieved by using genome sequences of 5000 and genotype data of 50,000 individuals combined with extensive health records regarding drug prescriptions and ADR diagnoses. The identified gene-ADR associations will be tested using functional studies. The results will serve as a basis for variants that can be included for preemptive pharmacogenomic testing, which could ultimately reduce the health and economic burden of low drug efficacy and unnecessary side effects caused by genetic variants.
The research group of pharmacogenetics is lead by Professor Dr. Lili Milani, lili.milani [ät] ut.ee
Studies the interactios between the genome and metabolome with regard to human diseases. This includes work with metabolomics data sets collected with NMR and mass-spectrometry. We search for associations between genomic markers and metabolite levels as well as more complicated patterns in these data sets with the intent to understand and predict common diseases. This work requires creating new bioinformatics algorithms, scripts and tools (C++, Phython) as well as conducting high pergormance cluster computations.
The research group of metabolomics and systems is lead by Associate Professor Dr. Toomas Haller, toomas.haller [ät] ut.ee
It is known that the genome apparently healthy individuals acutally harbors dozens of gene-disrupting variants (predicted to results in loss of function at the protein level). On the other hand, many phenotypic traits show inconsistent inheritance patterns due to penetrance and expressivity. The very first readout of genomic information is RNA, where celss have evolved several quality control mechanisms to minimize the impact of potentially harmful mutations. Our aim is to understand how mRNA regulation contributes to the buffering of such deleterious genetic variants.
The research group of mRNA is lead by Associate Professor Dr. Tarmo Annilo, tarmo.annilo [ät] ut.ee
The human intestinal tract is colonized by thousands of different species of microorganisms, collectively called the microbiota. The gut microbiome (collection of all microbial genes) encodes much more genes than the human genome and provides us with numerous complementary functions. The microbioal community has a critical role in many aspects of health, including immunit and metabolism. Our group addresses questions about the relationships between microbiome and human host, where we currently focus on two major ares: 1) we explore the host-microbiome interactions in development of type 2 diabetes and 2) elucidate the direct and indirect mechanisms through which the human microbiome shapes the efficacy and toxicity of commonly used drugs.
The research group of microbiome is lead by Associate Professor Dr. Elin Org, elin.org [ät] ut.ee
Research group of functional genomics is focused on understanding the molecular function of human genome variation. The group's broader scientific interest lies in understanding the genetic architecture of complex human phenotypes, focusing on intermediate molecular measurements (such as levels of gene expression in human tissues, cellular fractions and circulating small molecules) and human stature to estimate the role of both rare and common genetic variation of phenotypic outcomes through various models of inheritance (additive, recessive, epistatic and epigenetic). We implement a range of bioinformatics and genetic epidemiology techniques to map endophenotypes quantitive trait loci (QTL) and to annotate known disease associations with downstream molecular mechanisms.
The research group of functional genomics is lead by vice director, Professor Dr. Tõnu Esko, tonu.esko [ät] ut.ee
The bioinformatics research group handles the quality control and processing of multi-omics data and offers general bioinformatics support for all research groups within the Genome Centre. Method development plays an important role in the scientific activities of the group, including software for genome-wide association studies (GWAMA, MR-MEGA, SCOPA), as well as novel solutions for DNA copy number variant detection and analysis. In addition, the members of the group are involved in projects studying the genetic background of different traits and diseases related to metabolic health and female reproductive health.
The research group of functional genomics is lead by Professor Dr. Reedik Mägi, reedik.magi [ät] ut.ee