A5025231877- BRCA gene mutations in cancer
- Genetic Associations and Epidemiology
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Prenatal Screening and Diagnostics
- Molecular Biology Techniques and Applications
- Genetic factors in colorectal cancer
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Global Cancer Incidence and Screening
- Advanced Biosensing Techniques and Applications
- Nutrition, Genetics, and Disease
- Pancreatic and Hepatic Oncology Research
- Cancer-related Molecular Pathways
- Neonatal Health and Biochemistry
- Autoimmune and Inflammatory Disorders Research
- Hearing, Cochlea, Tinnitus, Genetics
- Advanced biosensing and bioanalysis techniques
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Metabolism and Genetic Disorders
Tartu University Hospital
2015-2025
University of Tartu
2016-2025
Estonian Biocentre
2000-2023
Competence Centre on Health Technologies (Estonia)
2022
East Tallinn Central Hospital
2021
John Wiley & Sons (United Kingdom)
2019
Hudson Institute
2019
Asper Biotech (Estonia)
2002-2005
Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the spectrum 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration phosphoproteomic...
DNA epigenetic modifications, such as methylation, are important regulators of tissue differentiation, contributing to processes both development and cancer. Profiling the tissue-specific methylome patterns will provide novel insights into normal pathogenic mechanisms, well help in future therapies. In this study, 17 somatic tissues from four autopsied humans were subjected functional genome analysis using Illumina Infinium HumanMethylation450 BeadChip, covering 486 428 CpG sites.Only 2%...
Genetic variation in the ABCR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), and age-related macular degeneration (AMD). Comparative genetic analyses of diagnostics have complicated by substantial allelic heterogeneity differences screening methods. To overcome these limitations, we designed a genotyping microarray (gene chip) for that includes all ∼400 disease-associated other...
The technology and application of arrayed primer extension (APEX) is presented. We describe an integrated system with DNA chip template preparation, multiplex on the array, fluorescence imaging, data analysis. method based upon array oligonucleotides, immobilized via 5' end a glass surface. A patient amplified by PCR, digested enzymatically, annealed to primers, which promote sites for template-dependent polymerase reactions using four unique fluorescently labeled dideoxy nucleotides....
Abstract Lung cancer is one of the deadliest types proven by poor survival and high relapse rates after surgery. Recently discovered microRNAs (miRNAs), small noncoding RNA molecules, play a crucial role in modulating gene expression networks are directly involved progression number human cancers. In this study, we analyzed profile 858 miRNAs 38 Estonian nonsmall cell lung (NSCLC) samples (Stage I II) 27 adjacent nontumorous tissue using Illumina miRNA arrays. We found that 39 were...
Despite of intense research in early cancer detection, there is a lack biomarkers for the reliable detection malignant tumors, including non-small cell lung (NSCLC). DNA methylation changes are common and relatively stable various types cancers, may be used as diagnostic or prognostic biomarkers.We performed profiling samples from 48 patients with stage I NSCLC 18 matching cancer-free using microarrays that cover promoter regions more than 14,500 genes. We correlated gene expression levels...
Published genetic risk scores for breast cancer (BC) so far have been based on a relatively small number of markers and are not necessarily using the full potential large-scale Genome-Wide Association Studies. This study aimed to identify an efficient polygenic predictor BC best available evidence assess its personalized prediction screening strategies.
Abstract Large biobanks have set a new standard for research and innovation in human genomics implementation of personalised medicine. The Estonian Biobank was founded quarter century ago, its biological specimens, clinical, health, omics, lifestyle data been included over 800 publications to date. What makes the biobank unique internationally is translational focus, with active efforts conduct clinical studies based on genetic findings, explore effects return results participants. In this...
Identification of mutations in the tumor suppressor gene TP53 has implications for molecular epidemiology and pathology human cancer. We have developed evaluated an arrayed primer extension assay covering both strands a region coding sequence containing more than 95% described so far TP53. On average, 97.5% can be analyzed from either sense or antisense strands, 81% strands. A patient DNA sample is amplified annealed to primers, which then promote polymerase reactions with four fluorescently...
Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, describe outcomes affected by such strategy.The Estonian Biobank Genome Center, University Tartu, comprises 52,274 individuals. Among 4776 participants exome or genome sequences,...
Abstract We have developed a method for arrayed primer extension (APEX) on an oligonucleotide microchip together with the 4-color fluoresence imaging equipment and supporting software, that allows analysis of DNA sequence changes in it. Mutation BRCA1 gene single nucleotide polymorphism (SNP) chip genotyping were used as model system. Chip surface chemistry, template preparation APEX reaction conditions optimised assay is ready to be implemented variety from SNP testing resequencing.
Summary Androgen receptor ( AR ) is a transcription factor that activated upon binding to testosterone (T) and implicated in regulating the expression of reproduction‐related genes. The human gene (Xq11‐12) spans 186,588 bp eight exons. N‐terminal transactivation domain encoded protein harbours two polymorphic stretches identical amino acids, polyglutamine tract (encoded by 8‐37 CAG ‐repeats) polyglycine 10‐30 GGN ‐repeats). We set forward analyse independent combinatory effects length these...
Abstract Most patients with pancreatic cancer present advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal presence of in an early stage are desperately needed. We aimed to identify new validate previously found plasma metabolomic associated stages cancer. Prediagnostic blood samples from individuals who were receive a diagnosis between 1 month 17 years sampling (N = 356) age- sex-matched controls 887) collected five large population cohorts...
Human mitochondrial DNA (mtDNA) research has entered a massively parallel sequencing (MPS) era, providing deep insight into mtDNA genomics and molecular diagnostics. Analysis can simultaneously include coding control regions, many samples be studied in parallel, even minor heteroplasmic changes detected. We investigated heteroplasmy using 16 different tissues from three unrelated males aged 40-54 years at the time of death. was enriched two independent overlapping long-range PCR amplicons...
Mutations in WNK1 and WNK4 cause familial hypertension, the Gordon syndrome. conserved noncoding regions were targeted to polymorphism screening using DHPLC DGGE. The scan identified an undescribed polymorphic AluYb8 insertion intron 10. Screening primates revealed that this Alu-insertion has probably occurred human lineage. Genotyping 18 populations from Europe, Asia, Africa (n = 854) indicated expansion of bearing chromosomes out Africa. allele frequency Sub-Saharan was ~3.3 times lower...
Somatic mosaicism denotes the presence of genetically distinct populations somatic cells in one individual who has developed from a single fertilised oocyte. Mosaicism may result mutation that occurs during postzygotic development and is propagated to only subset adult cells. Our aim was investigate both for copy-neutral loss heterozygosity (cn-LOH) events DNA copy number variations (CNVs) fully differentiated tissues. We studied panels tissue samples (11–12 tissues per individual) four...
Genetics has traditionally enabled the reliable diagnosis of patients with rare genetic disorders, thus empowering key role today's clinical geneticists in providing healthcare. With many novel technologies that have expanded toolkit, genetics is increasingly evolving beyond disease diagnostics. When placed a transition context-like we do here-clinical likely to become fully integral part future healthcare and expertise will be required outside traditional settings. We explore effects on...