Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) are two devastating neurodegenerative diseases that affect 100,000s of people globally. They have a severe adverse impact on society, yet there are currently no early diagnostic tools or disease-modifying therapies available. Despite their clinical heterogeneity, evidence points to these diseases being on...
Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5-15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. PCOS is highly heritable, but only a small proportion of this heritability can be...
The focus of this thesis is on evaluating, designing, and applying statistical methods that elucidate molecular mechanisms by seeking to understand the pathways that contribute to disease. Chapter 1 introduces the field and motivates the work in this thesis. Chapters 2, 3, and 4 describe original work. Chapter 5 recapitulates...
Gene regulatory networks (GRNs) are important abstractions of the complex regulatory interplays between genes, proteins, metabolites, and other molecular-level entities. Comprehensive GRNs provide high-level overviews of the topology of gene-gene interactions and their purposes, thereby enabling a comprehensive understanding of their role in phenotypic variation, disease mechanisms, and other biological...
Cells are complex, autonomous machines that integrate many environmental cues to execute a desired response. Though this property makes cells versatile, it presents significant design challenges when, to treat diseases, we must alter cellular responses. To understand changes to the complex regulatory pathways that cause diseases, studies often investigate the...