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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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In partial fulfillment of the requirements for the degree of
Doctor of Philosophy in Bioinformatics
in the School of Biological Sciences
Hector F. Espitia-Navarro
Defends his thesis:
Efficient Alignment-free Software Applications for Next Generation Sequencing-based Molecular Epidemiology
Monday, December 9th, 2019
11:00 AM Eastern Time
IBB Suddath Room 1128
Thesis Advisor:
Dr. King Jordan
School of Biological Sciences
Georgia Institute of Technology
Committee Members:
Dr. Srinivas Aluru
School of Computational Science and Engineering
Georgia Institute of Technology
Dr. Jung Choi
School of Biological Sciences
Georgia Institute of Technology
Dr. Lavanya Rishishwar
School of Biological Sciences
Georgia Institute of Technology
Dr. Leonard Mayer
School of Medicine
Emory University
Abstract
Public health agencies increasingly couple next generation sequencing (NGS) characterization of microbial genomes with bioinformatics analysis methods for molecular epidemiology. The overhead associated with the bioinformatics methods that are used for this purpose, in terms of both the required human expertise and computational resources, represents a critical bottleneck that limits the potential impact of microbial genomics on public health. This is particularly true for local public health agency laboratories, which are typically staffed with microbiologists who may not have substantial bioinformatics expertise or ready access to high-performance computational resources. There is a pressing need for bioinformatics solutions to genome-enabled molecular epidemiology that must be easy to use, computationally efficient, fast, and most importantly, highly accurate. This thesis research is focused on the development of an alignment-free algorithm for NGS data analysis and its implementation into turn-key software applications specifically tailored for genome-enabled molecular epidemiology and environmental microbial genomics. I explored a computational strategy based on k-mer frequencies to distinguish between sequences of interest in NGS read samples. By combining this strategy with an efficient data structure called Enhanced Suffix Array (ESA), I developed a base algorithm – STing – for the rapid analysis of unprocessed NGS reads. I further adapted and implemented this algorithm into a suite of software applications for sequence typing, gene detection, and gene-based taxonomic read classification. Benchmarking and validation analyses showed that STing is an ultrafast and accurate solution for genome-enabled molecular epidemiology, which performs better than existing bioinformatics methods for sequence typing and gene detection. To contribute to overcoming the limitation of bioinformatics infrastructure and expertise in public health laboratories, I developed WebSTing, a Web-platform that uses the STing algorithm to provide easy access to the accurate and rapid alignment-free automated characterization of WGS samples of bacterial isolates. Finally, to demonstrate the utility of the STing in problems beyond simple sequence typing and gene detection, I applied the alignment-free algorithm to two different areas: (1) public health, with the virulence gene profiling of Shiga toxin-producing Escherichia coli (STEC) isolates, and (2) environmental microbial genomics, with the nifH gene-based taxonomy classification of amplicon sequencing reads. I showed that STing performs better than the gold-standard method for STEC isolate characterization, and that it correctly classifies amplicon sequencing reads on simulated communities of nitrogen-fixing organisms.
