Caves are accessible windows into the shallow subsurface, serving as transitional ecosystems between the photosynthesis-dependent surface and the deeper subsurface. Without a source of solar energy to ultimately power carbon (C) fixation (photolithoautotrophy), cave ecosystems are either reliant on surface-derived nutrients, recovering reducing power from the microbial oxidation of redox-sensitive...
Cancer is a complex and heterogeneous disease characterized by aberrant gene regulation. Gene regulation is fundamentally orchestrated by the 3D genome organization which involves chromatin looping, compartmentalization, and the formation of topologically associating domains (TADs). Structural variations (SVs), such as genomic rearrangements, deletions, inversions, and duplications, are commonly observed in...
Bacterial infections (BI) are a frequent, expensive, and life-threatening condition for critically ill patients. For patients with serious BI, minimizing the time between admission to the
intensive care unit (ICU) and administration of appropriate antibiotic therapy is crucial to
improve prognosis. However, the current gold-standard for identifying the appropriate
antimicrobials...
Fat represents an important source of energy for ovarian cancer (OC) cells and is supplied either through import from the tumor milieu or via de novo lipogenesis. During fast tumor growth, when nutrients are scarce, lipogenesis becomes the primary source of fatty acids. Stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in...
Transfer of information across membranes is fundamental to the function of all organisms and is primarily initiated by transmembrane receptors. This is an allosteric process and involves conformational coupling between ligand-binding domain and signaling domain of a receptor. This allosteric mechanism of activation is unclear for many receptors. Moreover, for...
Breakthroughs in large-scale biological data collection have resulted in a wealth of -omics (genomics, metabolomics, etc.) datasets in the literature. However, the development of appropriate computational techniques for their analysis is lacking, yet crucial for fully extracting the rich information contained in these datasets. The work in this dissertation describes...
In 2009, the Health Information Technology for Economic and Clinical Health Act (HITECH) promoted national use of electronic health records (EHR) in the US by giving incentives to providers who adopt ‘meaningful use’ of EHRs. As of 2017, nearly 86% of office-based physicians had adopted EHRs. EHRs have rich information...
Circadian rhythms — physiological, behavioral, and metabolic oscillations with an approximate 24-h period — are controlled by an evolutionarily conserved set of core clock genes operating at the transcriptional and protein level. Entrainable by Zeitgebers (external environmental stimuli such as light, temperature, and food) that modulate time-of-day specific functions, the...
Modern data sets are increasingly vast, not only in the number of samples, but also in the number of measurements, or features, that they contain. This high-dimensionality poses a unique set of problems for data analysis due to a set of phenomena known as ``the curse of dimensionality.'' This thesis...
Macrophages are innate immune cells that are traditionally thought to be specialists in phagocytosis. More recent evidence suggest that macrophages reside in nearly every organ and readily adapt to local microenvironmental signals, leading to highly plastic phenotypes across and within tissues. Therefore, rather than treating it as a homogenous cell...
To combat the rise of antibiotic-resistant pathogens in clinical settings, it is necessary to understand which environments and conditions select for antibiotic resistance. Analysis of environments hypothesized to select for antibiotic resistance has been revolutionized by metagenomic sequencing. The metagenomic pool of DNA sequences can be probed in silico using...
Human complex diseases such as common cancers and diabetes are characterized by high molecular heterogeneity contributed by both genetic and non- genetic factors. This molecular heterogeneity can not only complicate diagnosis, risk stratification and patient care, but also lead to differential therapeutic response and treatment efficiency. Therefore, understanding the molecular...
The Escherichia coli ribosome is a molecular machine capable of sequence-defined polymerization of -amino acids into proteins, a feat unmatched by any other current synthetic catalyst. It is complex in its structure, comprised of 3 RNA parts (the 5S, 16S, and 23S ribosomal RNAs) and 54 ribosomal proteins (r-proteins). Efforts...
Mammalian transcriptional regulation is well-known to be complex and highly context dependent. Different genetic and epigenetic features, including single nucleotide polymorphisms (SNPs) that function as cis- or trans-expression quantitative trait loci (eQTLs), transcription factor (TF) interaction profile with cis-regulatory elements (CREs), methylation of CpG dinucleotide sequences, and histone modification that...
Prions are self-perpetuating, alternative protein conformations associated with neurological diseases and normal cellular functions. Saccharomyces cerevisiae contains many endogenous prions – providing a powerful system to study prionization. Previously, the Li Lab demonstrated that Swi1, a component of the SWI/SNF chromatin-remodeling complex, can form the prion [SWI+]. A small region,...
In the short amount of time that genetic manipulation has been possible through CRISPR technology, myriad applications have been developed. Results from one of the most promising applications of this technology, pooled screens, have shown that single guide RNAs (sgRNAs), RNA sequences used to target specific regions of the genome,...
Current genetic studies are largely biased towards European populations, leaving the discovery of genomics biomarkers and causative genetic variants unexplored in minority populations, such as African Americans. Meanwhile, African Americans are disproportionately affected by a variety of complex diseases and respond differently to many drug treatments. The disparity is due...
Uterine leiomyomas (fibroids) are a major source of gynaecologic morbidity in reproductive age women and are characterised by the excessive deposition of a disorganised extracellular matrix, resulting in rigid benign tumours. Clinically, leiomyoma patients usually present with pelvic pain, urinary incontinence, as well as heavy cyclic and non-cyclic bleeding. Curative...
Over 6 million adults in the United States have heart failure, a serious public health problem. Differences in the progression of heart failure are in part due to variability in sex, age, and genetic variation background including ancestry. Medical biobanks provide a resource to study this variability as they include...
The advent of sequencing technologies has generated a large amount of biological and medical data. These data such as genetic sequencing data and lab experimental evidence data can help understand critical biomedical problems. This dissertation makes contribution in three different but related applications in biomedical research. In Chapter 2, we...