Prof. Jaak Vilo (Institute of Computer Science UT)
Dr. Balaji Rajashekar (Institute of Computer Science UT)
Prof. Stephan Beck (University College London, United Kingdom)
Assoc. Prof. Anagha Joshi (University of Bergen, Norway)
Summary of the Thesis:
DNA contains the genetic information required for the growth and development of the organism. In addition to the nucleotide sequence, certain chemical modifications influence the activity of the DNA. The most studied DNA modification is DNA methylation, where a methyl group is added to the cytosine base of the DNA. DNA is often methylated within a genomic region, forming so- called “methylation patterns.” These “patterns” are involved in the regulation of gene expression by switching genes in and out of certain cells or adjusting their activity. Environmental factors strongly influence DNA methylation; wherein certain genomic regions may be methylated or unmethylated. Thus, methylation patterns serve as a mediator between the environment and genomes. Many of these “patterns” are inherited in normal biological processes. However, some of these patterns indicate the presence of the disease. For example, specific methylation patterns have been observed in diabetes, neurological disorders, and cancer. Therefore, methylation patterns are considered as biomarker candidates to characterize the progression of certain diseases or normal biological process. This thesis focuses on the study of DNA methylation in different tissues and conditions to identify potential biomarker candidates using various bioinformatics and statistical methods. In total, three studies were included in this thesis to investigate both tissue and endometriosis-specific biomarker candidates as well as changes in DNA methylation during the transition from pre-receptive to the receptive state of the endometrium. In addition, a novel and user-friendly web application MethSurv was developed in this thesis. MethSurv uses methylation and clinical data from the publicly available “The Cancer Genome Atlas” (TCGA). The MethSurv tool is aimed at assisting the scientific community in exploring methylation-based prognostic biomarkers.