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Title page for ETD etd-03262018-193456


Type of Document Dissertation
Author Eidem, Haley Rae
Author's Email Address haley.eidem@gmail.com
URN etd-03262018-193456
Title An integrative genomics approach to identifying genetic regulators of prematurity
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Patrick Abbot Committee Chair
Antonis Rokas Committee Co-Chair
Bill Ackerman Committee Member
Jim Patton Committee Member
Tony Capra Committee Member
Keywords
  • data integration
  • multi-omics
  • complex disease
  • transcriptomics
  • preterm birth
  • candidate gene ranking
Date of Defense 2018-03-14
Availability unrestricted
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.
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