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Microbial characteristics of chronic respiratory disease
Dissertation   Open access

Microbial characteristics of chronic respiratory disease

Joshua P. Earl
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2018
DOI:
https://doi.org/10.17918/t1y0-8k61
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Abstract

Medical sciences Respiratory organs--Diseases Moraxella Phylogeny--Molecular aspects Bioinformatics Molecular Biology
Respiratory illness is the third leading medical expense category in the United States. Chronic respiratory conditions were the third leading cause of death in the United States in 2011; there is therefore an urgent need for accurate clinical diagnostics, and deeper understanding of organisms associated with these diseases. This study examines in detail new DNA sequence technology that can be used to identify to the species level essentially all bacterial organisms present in clinical samples. A new bioinformatic pipeline designed specifically to leverage this new long read DNA sequence is introduced: MCSMRT. This new analytical method is validated with both simple, and complex mock communities illustrating this pipeline's sensitivity and specificity capabilities compared to previous efforts using short read technology. The methods are applied to 12 patient's sino-nasal surgery samples, showing the clinical relevance of this diagnostic. In addition, to further illustrate the power of genomic DNA sequence methods, Moraxella catarrhalis, the third leading cause of the chronic respiratory illness otitis media (OM) is characterized at a detailed genomic level. This new analysis examines the supragenome in unprecedented detail, including analysis of community composition, phylogenetic relatedness, virulence factor distribution, horizontal gene transfer, and antibiotic capabilities of 31 clinical isolates.

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