Systems approach to respiratory disease, A

Includes bibliographical references. ; Summer ; Systems-based approaches, including genomics, interactomics, and transcriptomics, allow for more comprehensive and more generalizable analyses than single gene or single drug approaches. These approaches often utilize techniques from network biology, statistics, and text mining to both decompose and analyze large sets of data. This dissertation utilizes the above techniques to further explore the interactions between respiratory diseases, chemicals, and genes, with a more specific focus on mycobacterial diseases. Respiratory diseases represent a high disease burden with over one billion people throughout the world afflicted by these diseases. Each year, approximately 9 million people become ill with tuberculosis (TB). The global burden of nontuberculous mycobacterial (NTM) infections is uncertain but NTM infections have become more common in the US than TB. Both of these diseases are ideal for systems-based approaches due to the interplay between genes, environmental stressors, and drugs. One third of people throughout the world have asymptomatic latent TB infection but only 5-15% of these individuals develop active TB disease. We are all exposed to NTM, which are ubiquitous in the environment, but only a very small proportion of people develop NTM disease. These patterns suggest a strong host component. In addition to this lack of understanding for identifying people who will develop TB or NTM disease, these illnesses are difficult to treat, with treatment often lasting between 6-18 months with multiple antibiotics. The first and second projects explore transcriptomic and genomic techniques to better understand Mycobacteria, from analyzing differences in metabolic function between species and exploring how to analyze transcriptomic data in samples containing mostly non-Mycobacterium tuberculosis RNA. The third project takes a broader approach, identifying host-based components to respiratory disease in general, with a sub-analysis representing the interaction of ...