UCLA

This dissertation is dedicated to enhancing the discovery of biologically relevant information forendophenotypes and biomarkers for complex brain disorders through the integration of data from multiple diverse omics domains, including genomics, transcriptomics, epigenomics, and metabolomics. Chapter 1 focuses on evaluating the functional genomic features captured by skin fibroblasts as an in vitro model for circadian studies, particularly within the context of Bipolar Disorder. This investigation utilizes longitudinal gene expression and chromatin accessibility data from six cell lines across thirteen timepoints. In Chapter 2, we delve into how distinct biological layers, including genetics and cerebrospinal fluid metabolites, contribute to understanding various aspects of Alzheimer's Disease pathology as reflected in established cerebrospinal fluid biomarkers, such as amyloid beta 42, total tau, and phosphorylated tau cerebrospinal fluid levels. Our findings underscore the utility of integrating functional genomics platforms to characterize the features that an in vitro model captures and assess their relevance for specific endophenotypes and disorders. Additionally, through CSF metabolomics analysis, we identify novel metabolites associated with phosphorylated tau and total tau CSF levels, such as Anserine and Fucose. This work signifies another step forward in advancing our comprehension of the underlying biology of complex brain disorders. By leveraging current technological advancements and addressing the challenges of integrating omics approaches, we aim to unravel new insights and avenues for diagnosis, treatment, and management of these debilitating conditions.