| dc.description.abstract | Preterm birth (PTB), or birth before 37 completed weeks of gestation, is the leading cause of newborn death worldwide. Despite its toll on human lives and economies, however, our understanding of its pathogenesis and prevention is limited. In this dissertation, I employed meta-analytical, comparative transcriptomic, and integrative genomic approaches to examine the pathways leading to prematurity. First, I synthesized the current landscape of transcriptomics research across PTB subtypes and uncovered gaps in our knowledge, particularly in cases that occur spontaneously (sPTB). Next, I sought to fill this gap by comparing gene expression profiles from placental tissue collected after human sPTB and term deliveries to identify genes whose dysregulation may contribute to sPTB pathogenesis. Furthermore, I refined these results with age matched control samples from rhesus macaque to tease apart sPTB-specific dysregulation from normal gestational age differences. Finally, I developed a desirability function-based approach to integrate the transcriptomics results with other heterogeneous sPTB ‘omics data. By applying this framework to GWAS, transcriptomics, epigenomics, and proteomics studies, I uncovered pathways related to homeostasis and muscle activity as candidates for future functional analyses. | |
