20.500.12556/RUL-171712 Bioinformacijska analiza genetskih dejavnikov progeroidnih sindromov Bioinformatic analysis of genetic factors in progeroid syndromes Progeroidni sindromi (PS) so heterogena skupina redkih dednih bolezni s kliničnimi znaki, ki spominjajo na pospešeno staranje, in kot taki predstavljajo uporaben model za razumevanje naravnih degenerativnih sprememb in mehanizmov človeškega staranja. Čeprav naj bi bilo do sedaj opisanih več kot 100 takšnih sindromov, so podatki o njih razpršeni po različnih virih, kar otežuje sintezo znanja in sistematično analizo. Namen magistrske naloge je bil zbrati in sistematično organizirati razpršene podatke o PS in z njimi povezanih genih ter z integrativno bioinformacijsko analizo genetskih dejavnikov poglobiti razumevanje te raznolike skupine motenj. Z vključitvijo podatkov iz 84 publikacij in podatkovne zbirke OMIM smo oblikovali celovito podatkovno zbirko ProGenDB, ki je s 144 geni in skupno 160 kliničnimi entitetami PS po naših podatkih največja objavljena zbirka tovrstnih motenj doslej. Zbrane podatke smo vizualizirali v obliki mreže povezav med genomom in fenomom, s čimer smo ponudili nov vpogled v genetsko in fenotipsko heterogenost PS. Obogatitvena analiza bioloških poti je potrdila, da so geni PS obogateni v bioloških procesih, povezanih z naravnim staranjem, pri čemer so posebej izstopali procesi popravljanja DNA. Mreža proteinskih interakcij (PPI) je razkrila tesen preplet med vpletenimi proteini, identificirani funkcionalni moduli v tej mreži pa so omogočili sistematičen pregled nad motenimi biološkimi procesi PS. Analize centralnosti so v mreži PPI izpostavile ključne tarče za nadaljnje raziskave. Identificirali smo tudi 14 genskih skupkov PS, v katerih so geni na genomu razporejeni v tesni bližini, vključno z dvema paroma prekrivajočih se genov, ter 48 genov PS, lociranih znotraj fragilnih regij genoma – znanih žarišč genomske nestabilnosti – in s tem izpostavili dodatne zanimive regije za nadaljnje analize. Naša raziskava predstavlja temelje za nadaljnje delo tako na področju PS kot tudi fiziološkega staranja. Nadaljnje izpopolnjevanje in širjenje vzpostavljene podatkovne zbirke ter poglobljene analize izpostavljenih genov in regij med drugim predstavljajo ključne cilje prihodnjih raziskav. Progeroid syndromes (PS) are a heterogeneous group of rare hereditary diseases with clinical features that resemble accelerated aging, and as such they serve as a useful model for understanding natural degenerative changes and the mechanisms of human aging. Although more than 100 such syndromes have been described to date, the information about them is scattered across various sources, making knowledge synthesis and systematic analysis difficult. The aim of this master’s thesis was to collect and systematically organize the dispersed data on PS and their associated genes and to deepen the understanding of this diverse group of disorders through integrative bioinformatic analysis of their genetic factors. By incorporating data from 84 publications and the OMIM database, we developed a comprehensive database named ProGenDB, which, with 144 genes and a total of 160 clinical PS entities, is, to our knowledge, the largest published collection of such disorders to date. We visualized the collected data in the form of a genome-phenome association network, offering a new perspective on the genetic and phenotypic heterogeneity of PS. The pathway enrichment analysis confirmed that PS genes are enriched in biological processes associated with natural aging, with DNA repair processes standing out in particular. The protein-protein interaction (PPI) network revealed a tight interconnection among the involved proteins, and the identified functional modules within this network enabled a systematic overview of the disrupted biological processes in PS. Centrality analyses within the PPI network highlighted key targets for further research. Furthermore, we identified 14 PS gene clusters in which the genes are arranged in close proximity on the genome, including two pairs of overlapping genes, and 48 PS genes located within fragile regions of the genome – known hotspots of genomic instability – thereby highlighting further regions of interest for future analysis. Overall, our study lays the foundation for future research in both the field of PS and physiological aging. Further refinement and expansion of the established database, as well as in-depth analyses of the highlighted genes and regions, represent key objectives for upcoming research efforts. progeroidni sindromi staranje bioinformatika podatkovna zbirka mreža genom-fenom biološke poti mreža proteinskih interakcij genski skupki prekrivanje genov fragilne genomske regije progeroid syndromes aging bioinformatics database genome-phenome network biological pathways gene clusters overlapping genes fragile genomic regions true false true Slovenski jezik Angleški jezik Magistrsko delo/naloga 2025-08-31 07:17:00 2025-08-31 07:17:05 2025-09-16 04:00:55 0000-00-00 00:00:00 2025 0 0 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2025-08-28 261890 247163907 50859.pdf 50859.pdf 1 3EFDB6263821985EE59F2DE883972BF5 59cee10ad92b887e8ca9f341185e218bf72a875ddab042d047e3d0c42012b92f 9881ea33-8629-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=215094 Biotehniška fakulteta 0 0 0