KOCMANOVÁ, K. Genetické variace u onemocnění koronárních tepen [online]. Brno: Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií. 2021.
Studentka Klára Kocmanová se ve své práci zabývá podrobným popisem genetiky onemocnění koronárních tepen a způsoby analýzy dat vzniklých v rámci velkých projektů zaměřených do této oblasti. Během řešení práce si Klára počínala nadstandardně ve všech oblastech hodnocení. Literární rešerše v úvodní části čerpá z více než dostatečného počtu 51 citací, ze kterých jsou informace efektivně včleněny a logicky uspořádány do textu. Daná problematika je psána čtivou formou, navíc v anglickém jazyce. Jádro práce - bioinformatická analýza byla provedena za účelem studia vybraných lokusů s cílem odhadnout výskyt rizikových variací. Variace byly anotovány a bylo identifikováno 68 genů a 10 pseudogenů spojenych s onemocněním koronárních tepen. Celý text svědčí o zvládnutí netriviálního multioborového zadání. Vypracování celé práce bylo pečlivé a samostatné, se zájmem o rešeršní i analytickou činnost, s pravidelnými konzultacemi dílčích výsledků. Zadání považuji za splněné, práci doporučuji k obhajobě.
Student Klara Kocmanova thesis is focussed on the research of genetic variants in Coronary Artery Disease (CAD). The study has many facets to begin with and is focussed on multiple factors that contribute to CAD development. The text of the thesis is around 39 pages plus 51 relevant references. The detailed work is divided into 3 chapters followed by bioinformatics and statistical analysis to validate the data. The first chapter deals with the anatomy, histology, and pathophysiology of CAD. The second chapter focuses on the current knowledge of the genetics of coronary artery disease. The third chapter mentions two genomic projects that have contributed to studying variations in coronary artery disease and the means of reading data from their databases. Overall, the work is very well executed. The rationale behind the problem, previous research findings, and the methodology employed to explain the missing CAD heritability and allelic heterogeneity is very well studied and explained. The experiments incorporated to identify Genome-wide significant loci for CAD has been perfectly carried out. Klara incorporated the project with the help of 1000 Genomes Project and CARDIoGRAM plus CD4 consortium. This led to 1000 Genomes-based linkage disequilibrium reference panel. The selection operator for jointly analysing multiple variants was applied to the loci discovered in 1000 Genomes-based genome-wide association meta-analysis performed by CARDIoGRAM plus CD4 consortium. The work further extends and explains the missing CAD heritability about allelic heterogeneity that were not discovered in a standard GWAS. Allelic heterogeneity was assessed by the LASSO regression model in 1000 Genomes-based genome-wide meta-analysis. Two datasets were used, additive and recessive. Manhattan plots were constructed to identify genome-wide significant loci by using SOJO package in R. The study finally identified details about 72 genes that is associated with CAD. The generated graphs in support of Linkage Disequilibrium (LD) matrixes for recessive and additive loci provide vital information’s. Tables detailing about significant genetic variants from the additive and recessive dataset provides important leads for future research opportunities. This includes genes that are linked with lipid metabolism, proinflammatory, and thrombogenic factors, vascular remodelling, and high blood pressure. The findings are in accordance with multi-targeted drug designing in coronary artery disease. Some section contains typos, but their numbers are very low and specific. The student should have taken care in representing “additive “and “recessive” data carefully as repetitive mistakes can be seen in the Graphical and text representation in the manuscript which creates confusion at times. Overall, the work has its merits for future research. Professional level approach in solving the problem is appreciated. Klara approached to solve the problem with the best available databases and tools available. The results and discussion part are clearly written and self-explainable. The presentation level and logical continuity of the problem addressed are without flaws and provides a sequential flow of the work. I evaluate the thesis with positive remarks. It meets the requirements of the assignment. Klara has provided important results that can be used as a lead to further extend the work with multi-targeted drug designing. This will allow to find probable lead compounds that can interact with several genes/targets related to coronary artery disease.
eVSKP id 134399