Life Sciences Commons^™

Bayesian Networks To Assess The Newborn Stool Microbiome, William E. Bennett Jr.

McKelvey School of Engineering Theses & Dissertations

In human stool, a large population of bacterial genes and transcripts from hundreds of genera coexist with host genes and transcripts. Assessments of the metagenome and transcriptome are particularly challenging, since there is a great deal of sequence overlap among related species and related genes. We sequenced the total RNA content from stool samples in a neonate using previously-described methods. We then performed stepwise alignment of different populations of RNA sequence reads to different indices, including ribosomal databases, the human genome, and all sequenced bacterial genomes. Each pool of RNA at each alignment step was subjected to compression to assess …

Development Of Steady-State And Dynamic Flux Models For Broad-Scope Microbial Metabolism Analysis, Lian He

McKelvey School of Engineering Theses & Dissertations

Flux analysis techniques, including flux balance analysis (FBA) and 13C-metabolic flux analysis (MFA), can characterize carbon and energy flows through a cells metabolic network. By employing both 13C-labeling experiments and nonlinear programming, 13C-MFA provides a rigorous way of examining cell flux distributions in the central metabolism. FBA, on the other hand, gives a holistic review of optimal fluxomes on the genome scale. In this dissertation, flux analysis techniques were constructed to investigate the microbial metabolisms.

First, an open-source and programming-free platform of 13C-MFA (WUFlux) with a user-friendly interface in MATLAB was developed, which allowed both mass isotopomer distribution (MID) analysis …

Application Of Genomic Technologies To Study Infertility, Nicholas Rui Yuan Ho

Arts & Sciences Electronic Theses and Dissertations

An estimated one in eight couples in the United States are diagnosed with infertility. There is a significant genetic contribution to infertility, with estimates of heritability ranging from 0.2 to 0.5. We know surprisingly little about the genetic causes, with only slightly more than a hundred genes known to cause human infertility. I have been translating recent advances in genomics to study infertility in a more efficient manner, in order to improve our knowledge of the genetic causes. By using high throughput genomics and proteomics datasets from other groups, I was able to feed that into a machine learning algorithm …

Understanding The Interactions Of Developing Thymocytes And Antigen Presenting Cells In The Thymic Medulla, Justin Shaun Arnold Perry

Arts & Sciences Electronic Theses and Dissertations

Various thymic APC subsets have been invoked in deletional tolerance and Treg cell induction, but previous studies either assessed total T cell numbers or used TCR transgenic lines, obscuring roles that individual thymic APC subsets might serve for particular antigen-specific T cell populations. Utilizing T cell receptor sequencing, we found that medullary thymic epithelial cells (mTECs) and bone marrow-derived (BM) APCs delete or select unique conventional and Treg cell TCR repertoires, demonstrating distinct roles for these APCs. We show that BM APCs and mTECs each contribute to Aire-dependent T cell tolerance development, albeit through either cooperative or autologous antigen presentation …