Title Integrative multi-omics data analysis methods: vascular cognitive impairment case /
Translation of Title Metodai integruotai daugiaomikinių duomenų analizei: kraujagyslinio kognityvinio sutrikimo atvejis.
Authors Milčiūtė, Milda
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Pages 108
Keywords [eng] Kraujagyslinis kognityvinis sutrikimas, demencija, daugiaomikinių duomenų analizė, genomika, epigenomika, transkriptomika, metabolomika, Rac/Rho GTPazės signalizacijos kelias, bioinformatika, vascular cognitive impairment, dementia, multi-omics data analysis, genomics, epigenomics, transcriptomics, metabolomics, Rac/Rho GTPase signaling, bioinformatics.
Abstract [eng] Vascular cognitive impairment (VCI) represents a significant and growing contributor to dementia, yet its underlying molecular mechanisms remain incompletely understood. To address this gap, we employed an integrative multi-omics approach to characterize molecular alterations in post-mortem brain tissue, providing a comprehensive view of VCI-associated changes through the integration of genomics, epigenomics, transcriptomics, and metabolomics data. Our analysis revealed a consistent pattern of dysregulation in the Rac/Rho GTPase signaling pathway across multiple omics layers. Genomic analysis showed an enrichment of specific genetic variants within genes of this pathway. Epigenomic profiling demonstrated widespread hypermethylation, particularly affecting Rac/Rho GTPase-related genes. Transcriptomic analysis further revealed altered gene expression and splicing within this pathway, alongside changes in signaling related to hypoxia. These findings suggest that Rac/Rho GTPase signaling could be one of the key contributors to VCI pathophysiology. Furthermore, integrative analysis of epigenomics, genomics and metabolomics data highlighted significant alterations in the associations between methylation regions, transcripts, and metabolite levels. Notably, we observed altered interactions between Rac/Rho GTPase-related genes expression and methylation and specific lipid classes, including diacylglycerols (DAGs) and phosphatidylethanolamines (PEs), as well as isobutyrate. This suggests that epigenetic dysregulation of Rac/Rho GTPase signaling contributes to metabolic disturbances, particularly in lipid pathways, which are critical for neurovascular function. In conclusion, this study demonstrates the power of multi-omics integration to uncover complex molecular relationships in VCI. The consistent identification of Rac/Rho GTPase pathway disruption across omics layers, alongside its interplay with oxidative stress and altered lipid metabolism, highlights this pathway as a potential therapeutic target. A deeper understanding of these mechanisms may pave the way for the development of novel interventions aimed at mitigating vascular damage and cognitive decline in VCI.
Dissertation Institution Vilniaus universitetas.
Type Master thesis
Language English
Publication date 2025