EPIGENOMIC AND EPITRANSCRIPTOMIC LANDSCAPE: ANALYSIS, PERFORMANCE ASSESSMENT, AND INTEGRATIVE MULTI-OMICS PROFILING IN HUMAN COLORECTAL CANCER

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2023

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The interplay between genetic and epigenetic factors is crucial in the onset and progression of colorectal cancer (CRC), a disease characterized by its complexity and high morbidity and mortality rates globally. This dissertation is focused on unraveling the roles of epigenomic and epitranscriptomic modifications in CRC, with the aim of identifying significant biomarkers and characterizing their functional implications through advanced bioinformatics and machine learning techniques.The first part established a foundation by examining DNA methylation, a crucial epigenetic mechanism. It delved into whole-genome bisulfite sequencing (WGBS), presenting a detailed comparison of methodologies and tools for analyzing DNA methylation patterns. This set the stage for understanding aberrant methylation in CRC, highlighting its significance in disease pathology, and offering insights into the complexities of epigenomic profiling. Building upon this, the second part expanded the scope to include a broader range of epigenetic methods. It presented a multi-platform assessment, utilizing several human cell lines to evaluate the reproducibility and efficiency of different genome-wide methylome sequencing protocols. This comprehensive characterization not only benchmarked current methods but also linked DNA methylation patterns to the wider epigenomic alterations observed in CRC. Subsequently, the final part evaluated m6A MeRIP-Seq data analysis pipelines, focusing on their sensitivity and specificity in detecting and quantifying m6A modifications, ensuring that the results can reliably inform about the presence and potential role of m6A modifications in CRC. Utilizing the selected m6A MeRIP-Seq pipelines in conjunction with RNA sequencing data, the analyses provide a comprehensive epitranscriptomic characterization of CRC. This involved identifying novel m6A modification patterns that are functionally relevant to CRC's development and progression. Furthermore, the research delved into the interaction between epitranscriptomic alterations and their subsequent impact on gene expression, signaling pathways, and the tumor microenvironment, thereby providing a holistic view of the molecular dynamics at play in CRC. This multifaceted approach endeavors to bridge the gap between epigenomic and epitranscriptomic research, offering a thorough understanding of their implications in CRC. The insights gained from this study aim to contribute to the field of cancer genomics, potentially leading to the development of new diagnostic and therapeutic strategies.

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Bioinformatics, Algorithsm comparison, Colorectal Cancer, DNA methylation, Epigenomic, Epitranscriptomic, RNA methylation

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108 pages

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