ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
Displaying 1 - 4 of 4
Filtering by
- All Subjects: Bioinformatics
Description
Genomic and proteomic sequences, which are in the form of deoxyribonucleic acid (DNA) and amino acids respectively, play a vital role in the structure, function and diversity of every living cell. As a result, various genomic and proteomic sequence processing methods have been proposed from diverse disciplines, including biology, chemistry, physics, computer science and electrical engineering. In particular, signal processing techniques were applied to the problems of sequence querying and alignment, that compare and classify regions of similarity in the sequences based on their composition. However, although current approaches obtain results that can be attributed to key biological properties, they require pre-processing and lack robustness to sequence repetitions. In addition, these approaches do not provide much support for efficiently querying sub-sequences, a process that is essential for tracking localized database matches. In this work, a query-based alignment method for biological sequences that maps sequences to time-domain waveforms before processing the waveforms for alignment in the time-frequency plane is first proposed. The mapping uses waveforms, such as time-domain Gaussian functions, with unique sequence representations in the time-frequency plane. The proposed alignment method employs a robust querying algorithm that utilizes a time-frequency signal expansion whose basis function is matched to the basic waveform in the mapped sequences. The resulting WAVEQuery approach is demonstrated for both DNA and protein sequences using the matching pursuit decomposition as the signal basis expansion. The alignment localization of WAVEQuery is specifically evaluated over repetitive database segments, and operable in real-time without pre-processing. It is demonstrated that WAVEQuery significantly outperforms the biological sequence alignment method BLAST for queries with repetitive segments for DNA sequences. A generalized version of the WAVEQuery approach with the metaplectic transform is also described for protein sequence structure prediction. For protein alignment, it is often necessary to not only compare the one-dimensional (1-D) primary sequence structure but also the secondary and tertiary three-dimensional (3-D) space structures. This is done after considering the conformations in the 3-D space due to the degrees of freedom of these structures. As a result, a novel directionality based 3-D waveform mapping for the 3-D protein structures is also proposed and it is used to compare protein structures using a matched filter approach. By incorporating a 3-D time axis, a highly-localized Gaussian-windowed chirp waveform is defined, and the amino acid information is mapped to the chirp parameters that are then directly used to obtain directionality in the 3-D space. This mapping is unique in that additional characteristic protein information such as hydrophobicity, that relates the sequence with the structure, can be added as another representation parameter. The additional parameter helps tracking similarities over local segments of the structure, this enabling classification of distantly related proteins which have partial structural similarities. This approach is successfully tested for pairwise alignments over full length structures, alignments over multiple structures to form a phylogenetic trees, and also alignments over local segments. Also, basic classification over protein structural classes using directional descriptors for the protein structure is performed.
ContributorsRavichandran, Lakshminarayan (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Spanias, Andreas S (Thesis advisor) / Chakrabarti, Chaitali (Committee member) / Tepedelenlioğlu, Cihan (Committee member) / Lacroix, Zoé (Committee member) / Arizona State University (Publisher)
Created2011
Description
Building mathematical models and examining the compatibility of their theoretical predictions with empirical data are important for our understanding of evolution. The rapidly increasing amounts of genomic data on polymorphisms greatly motivate evolutionary biologists to find targets of positive selection. Although intensive mathematical and statistical studies for characterizing signatures of positive selection have been conducted to identify targets of positive selection, relatively little is known about the effects of other evolutionary forces on signatures of positive selection. In this dissertation, I investigate the effects of various evolutionary factors, including purifying selection and population demography, on signatures of positive selection. Specifically, the effects on two highly used methods for detecting positive selection, one by Wright's Fst and its analogues and the other by footprints of genetic hitchhiking, are investigated. In Chapters 2 and 3, the effect of purifying selection on Fst is studied. The results show that purifying selection intensity greatly affects Fst by modulating allele frequencies across populations. The footprints of genetic hitchhiking in a geographically structured population are studied in Chapter 4. The results demonstrate that footprints of genetic hitchhiking are significantly influenced by geographic structure, which may help scientists to infer the origin and spread of the beneficial allele. In Chapter 5, the stochastic dynamics of a hitchhiking allele are studied using the diffusion process of genetic hitchhiking conditioned on the fixation of the beneficial allele. Explicit formulae for the conditioned two-locus diffusion process of genetic hitchhiking are derived and stochastic aspects of genetic hitchhiking are investigated. The results in this dissertation show that it is essential to model the interaction of neutral and selective forces for correct identification of the targets of positive selection.
ContributorsMaruki, Takahiro (Author) / Kim, Yuseob (Thesis advisor) / Taylor, Jesse E (Thesis advisor) / Greenwood, Priscilla E (Committee member) / Hedrick, Philip W (Committee member) / Rosenberg, Michael S. (Committee member) / Arizona State University (Publisher)
Created2011
Description
Rapid advancements in genomic technologies have increased our understanding of rare human disease. Generation of multiple types of biological data including genetic variation from genome or exome, expression from transcriptome, methylation patterns from epigenome, protein complexity from proteome and metabolite information from metabolome is feasible. "Omics" tools provide comprehensive view into biological mechanisms that impact disease trait and risk. In spite of available data types and ability to collect them simultaneously from patients, researchers still rely on their independent analysis. Combining information from multiple biological data can reduce missing information, increase confidence in single data findings, and provide a more complete view of genotype-phenotype correlations. Although rare disease genetics has been greatly improved by exome sequencing, a substantial portion of clinical patients remain undiagnosed. Multiple frameworks for integrative analysis of genomic and transcriptomic data are presented with focus on identifying functional genetic variations in patients with undiagnosed, rare childhood conditions. Direct quantitation of X inactivation ratio was developed from genomic and transcriptomic data using allele specific expression and segregation analysis to determine magnitude and inheritance mode of X inactivation. This approach was applied in two families revealing non-random X inactivation in female patients. Expression based analysis of X inactivation showed high correlation with standard clinical assay. These findings improved understanding of molecular mechanisms underlying X-linked disorders. In addition multivariate outlier analysis of gene and exon level data from RNA-seq using Mahalanobis distance, and its integration of distance scores with genomic data found genotype-phenotype correlations in variant prioritization process in 25 families. Mahalanobis distance scores revealed variants with large transcriptional impact in patients. In this dataset, frameshift variants were more likely result in outlier expression signatures than other types of functional variants. Integration of outlier estimates with genetic variants corroborated previously identified, presumed causal variants and highlighted new candidate in previously un-diagnosed case. Integrative genomic approaches in easily attainable tissue will facilitate the search for biomarkers that impact disease trait, uncover pharmacogenomics targets, provide novel insight into molecular underpinnings of un-characterized conditions, and help improve analytical approaches that use large datasets.
ContributorsSzelinger, Szabolcs (Author) / Craig, David W. (Thesis advisor) / Kusumi, Kenro (Thesis advisor) / Narayan, Vinodh (Committee member) / Rosenberg, Michael S. (Committee member) / Huentelman, Matthew J (Committee member) / Arizona State University (Publisher)
Created2015
Description
Peptide microarrays have been used in molecular biology to profile immune responses and develop diagnostic tools. When the microarrays are printed with random peptide sequences, they can be used to identify antigen antibody binding patterns or immunosignatures. In this thesis, an advanced signal processing method is proposed to estimate epitope antigen subsequences as well as identify mimotope antigen subsequences that mimic the structure of epitopes from random-sequence peptide microarrays. The method first maps peptide sequences to linear expansions of highly-localized one-dimensional (1-D) time-varying signals and uses a time-frequency processing technique to detect recurring patterns in subsequences. This technique is matched to the aforementioned mapping scheme, and it allows for an inherent analysis on how substitutions in the subsequences can affect antibody binding strength. The performance of the proposed method is demonstrated by estimating epitopes and identifying potential mimotopes for eight monoclonal antibody samples.
The proposed mapping is generalized to express information on a protein's sequence location, structure and function onto a highly localized three-dimensional (3-D) Gaussian waveform. In particular, as analysis of protein homology has shown that incorporating different kinds of information into an alignment process can yield more robust alignment results, a pairwise protein structure alignment method is proposed based on a joint similarity measure of multiple mapped protein attributes. The 3-D mapping allocates protein properties into distinct regions in the time-frequency plane in order to simplify the alignment process by including all relevant information into a single, highly customizable waveform. Simulations demonstrate the improved performance of the joint alignment approach to infer relationships between proteins, and they provide information on mutations that cause changes to both the sequence and structure of a protein.
In addition to the biology-based signal processing methods, a statistical method is considered that uses a physics-based model to improve processing performance. In particular, an externally developed physics-based model for sea clutter is examined when detecting a low radar cross-section target in heavy sea clutter. This novel model includes a process that generates random dynamic sea clutter based on the governing physics of water gravity and capillary waves and a finite-difference time-domain electromagnetics simulation process based on Maxwell's equations propagating the radar signal. A subspace clutter suppression detector is applied to remove dominant clutter eigenmodes, and its improved performance over matched filtering is demonstrated using simulations.
The proposed mapping is generalized to express information on a protein's sequence location, structure and function onto a highly localized three-dimensional (3-D) Gaussian waveform. In particular, as analysis of protein homology has shown that incorporating different kinds of information into an alignment process can yield more robust alignment results, a pairwise protein structure alignment method is proposed based on a joint similarity measure of multiple mapped protein attributes. The 3-D mapping allocates protein properties into distinct regions in the time-frequency plane in order to simplify the alignment process by including all relevant information into a single, highly customizable waveform. Simulations demonstrate the improved performance of the joint alignment approach to infer relationships between proteins, and they provide information on mutations that cause changes to both the sequence and structure of a protein.
In addition to the biology-based signal processing methods, a statistical method is considered that uses a physics-based model to improve processing performance. In particular, an externally developed physics-based model for sea clutter is examined when detecting a low radar cross-section target in heavy sea clutter. This novel model includes a process that generates random dynamic sea clutter based on the governing physics of water gravity and capillary waves and a finite-difference time-domain electromagnetics simulation process based on Maxwell's equations propagating the radar signal. A subspace clutter suppression detector is applied to remove dominant clutter eigenmodes, and its improved performance over matched filtering is demonstrated using simulations.
ContributorsO'Donnell, Brian (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Bliss, Daniel (Committee member) / Johnston, Stephen A. (Committee member) / Kovvali, Narayan (Committee member) / Tepedelenlioğlu, Cihan (Committee member) / Arizona State University (Publisher)
Created2014