Επεξεργασία και ανάλυση βιολογικών δεδομένων με τη χρήση ευφυών υπολογιστικών μεθόδων

Abstract

This thesis focuses on the development and implementation of intelligent computational methods for extending the use of biological data as well as the organization, processing, analysis and understanding of these data. The uttermost aim is to build upon the gained conclusions towards deciphering the genetic background of diseases and consequently facilitate treatment in an efficient and targeted manner. The study in centered around an inductive research framework where we proceed from the specific to the general. The research starts from the lowest level of proteins organization, the primary structure, by studying the bonds developed between the amino acids. Next, we analyze the interactions among protein molecules, specifically focusing on proteins that are either partially or fully disordered, aka unstructured. Due to their conformational flexibility they are often found to interact with a multitude of protein molecules, hence they are involved with many cellular functions as well as the induction of severe diseases. Afterwards, we aim to extend and combine the analysis from the microscopic level with macroscopic observations and data. Specifically, we collect and analyze biological data on cellular and systemic organism functions, coupled with clinical data (i.e. medical history and imaging modalities) referring to the phenotypic level of anatomical entities and the organism as a whole. We apply this multilevel and multiparametric analysis in a complex disease like cancer - and more specifically oral cancer - which has manifestations in all levels of human physiology. The contribution of this thesis is identified in the following areas: (i) the emergence of the biological mechanism that determines the conformation of the peptide bond, (ii) the systematic identification of functionalities associated with protein regions containing cis peptide bonds, (iii) the extraction of sequence patterns mediating the functional role of disordered proteins, (iv) the systematic unraveling of how disordered proteins are involved with the induction of several genetic diseases, (v) to study and analyze the genetic background of multifactorial diseases (oral cancer) and pinpoint the genetic factors dictating the disease progression, (vi) the orchestrated analysis of heterogeneous clinical and genomic data, in a complementary manner in order to capture multilevel disease perturbations ranging from the cellular level, to the tissue phenotype and the organism as a whole