subject:(Genomics)

University of Georgia

1. Smith, Shannon Nicole. Uncertainty of the dependent variable in genome-wide association studies.

Degree: PhD, Animal and Dairy Science, 2013, University of Georgia

URL: http://purl.galileo.usg.edu/uga_etd/smith_shannon_n_201308_phd

► The use of high throughput technology has the potential to provide insight into the underlying biological mechanisms of several important complex traits. Unfortunately this information… (more)

▼ The use of high throughput technology has the potential to provide insight into the underlying biological mechanisms of several important complex traits. Unfortunately this information comes at a cost, sometimes in terms of low accuracy and poor quality of the data. One application of genomics in humans is the diagnoses of diseases such as bipolar disorder, Alzheimer’s disease, and cancer. However in order to correctly predict disease statuses, methods should be trained on datasets containing no errors. In the case for most conditions this is seldom the case, as mis-diagnostic errors are prevalent due to overlapping symptoms and lack of precise diagnostic tools. Therefore, a new approach for dealing with misclassification was developed and applied to simulated data sets where case and control observations were randomly switched and with varying odds ratios of influential SNPs, to examine the effects of potential misclassification on diagnostic accuracy. The cases when misclassification was ignored resulted in limited predictive power of the model. When the misclassification algorithm was applied, the predictive power increased across all scenarios demonstrating the effectiveness of the misclassification algorithm. Additionally in livestock applications, genomic technology is used to detect genetic variants associated with economically important traits as well as to estimate genomic enhanced breeding values to be used in animal selection. For genome wide association studies (GWAS) in animal applications the dependent variable is often a ‘pseudo’ phenotype (estimated breeding values, de-regressed breeding values, etc.). Being estimates, these pseudo-phenotypes carry a certain level of inaccuracy or uncertainty. In some situations, such uncertainty is large and it is not constant across observations. Consequently, using these estimates directly as dependent variables in the GWAS can be problematic because the residual variance of the model is composed of two components (sampling variance and the error variance) that current methods are unable to accommodate. Thus, we developed and implemented a new procedure that correctly accounts for both components of the residual variance leading to an increase in accuracies of the estimated genomic breeding values. The proposed method was evaluated with real and simulated data. Advisors/Committee Members: Romdhane Rekaya.

Subjects/Keywords: Genomics

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APA (6^th Edition):

Smith, S. N. (2013). Uncertainty of the dependent variable in genome-wide association studies. (Doctoral Dissertation). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/smith_shannon_n_201308_phd

Chicago Manual of Style (16^th Edition):

Smith, Shannon Nicole. “Uncertainty of the dependent variable in genome-wide association studies.” 2013. Doctoral Dissertation, University of Georgia. Accessed February 18, 2020. http://purl.galileo.usg.edu/uga_etd/smith_shannon_n_201308_phd.

MLA Handbook (7^th Edition):

Smith, Shannon Nicole. “Uncertainty of the dependent variable in genome-wide association studies.” 2013. Web. 18 Feb 2020.

Vancouver:

Smith SN. Uncertainty of the dependent variable in genome-wide association studies. [Internet] [Doctoral dissertation]. University of Georgia; 2013. [cited 2020 Feb 18]. Available from: http://purl.galileo.usg.edu/uga_etd/smith_shannon_n_201308_phd.

Council of Science Editors:

Smith SN. Uncertainty of the dependent variable in genome-wide association studies. [Doctoral Dissertation]. University of Georgia; 2013. Available from: http://purl.galileo.usg.edu/uga_etd/smith_shannon_n_201308_phd

2. Urban, John. The genome and DNA puff sequences of the fungus fly, Sciara coprophila, and genome-wide methods for studying DNA replication.

Degree: Department of Molecular Biology, Cell Biology and Biochemistry, 2017, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:733543/

► DNA replication initiates from any given origin at most once per cell cycle to ensure perfect duplication of the hereditary material. DNA re-replication occurs when… (more)

▼ DNA replication initiates from any given origin at most once per cell cycle to ensure perfect duplication of the hereditary material. DNA re-replication occurs when an origin initiates more than once. This can lead to DNA damage, gene amplification, and genomic rearrangements, all hallmarks of cancer. Whereas it is difficult to study re-replication in cancer cells, the fungus fly Sciara coprophila is a tractable alternative where re-replication occurs in the DNA puffs of giant polytene chromosomes in larval salivary glands during normal development. The DNA sequence for only one of many DNA puffs was known, preventing identification of shared motifs. Progress has also been thwarted by the absence of a genome sequence, necessary for genomics approaches. In this thesis, I present the first draft of the Sciara coprophila genome sequence, assembled using Illumina short reads, long single-molecule reads from Pacific Biosciences and Oxford Nanopore, and optical maps from BioNano Genomics. Using the Oxford Nanopore MinION, I established protocols to obtain high quality, ultra-long reads that exceed 100 kb in some cases, which were important in assembling multi-megabase contigs. RNA sequencing of the transcriptomes of both sexes across the lifecycle facilitated annotation of genes hidden in the genome sequence. High throughput sequencing of the salivary gland genome throughout the DNA re-replication stages identified multiple DNA puff sequences, which were confirmed with qPCR, and in some cases mapped by Fluorescence in situ Hybridization (FISH) to corresponding DNA puffs. Mapping the origins where DNA re-replication begins is still needed to locate cis-regulatory elements. Toward this goal, I have refined the genome-wide origin mapping technique Nascent Strand sequencing (NS-seq) by inclusion of important controls and found that nucleosomes are phased around a subset of origins near G-quadruplex motifs in the human genome. Moreover, I describe my progress in developing new single-molecule, genome-wide origin mapping techniques. Overall, this thesis presents the genome and DNA puff sequences of Sciara coprophila as well as methods to map the re-replication origins, thereby establishing a foundation to unravel the mechanism of site-specific DNA re-replication. Advisors/Committee Members: Gerbi, Susan (Advisor), Larschan, Erica (Reader), Mark Welch, David (Reader), Raphael, Benjamin (Reader), Johnson, Mark (Reader).

Subjects/Keywords: Genomics

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APA (6^th Edition):

Urban, J. (2017). The genome and DNA puff sequences of the fungus fly, Sciara coprophila, and genome-wide methods for studying DNA replication. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:733543/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Urban, John. “The genome and DNA puff sequences of the fungus fly, Sciara coprophila, and genome-wide methods for studying DNA replication.” 2017. Thesis, Brown University. Accessed February 18, 2020. https://repository.library.brown.edu/studio/item/bdr:733543/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Urban, John. “The genome and DNA puff sequences of the fungus fly, Sciara coprophila, and genome-wide methods for studying DNA replication.” 2017. Web. 18 Feb 2020.

Vancouver:

Urban J. The genome and DNA puff sequences of the fungus fly, Sciara coprophila, and genome-wide methods for studying DNA replication. [Internet] [Thesis]. Brown University; 2017. [cited 2020 Feb 18]. Available from: https://repository.library.brown.edu/studio/item/bdr:733543/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Urban J. The genome and DNA puff sequences of the fungus fly, Sciara coprophila, and genome-wide methods for studying DNA replication. [Thesis]. Brown University; 2017. Available from: https://repository.library.brown.edu/studio/item/bdr:733543/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne

3. Rane, Rahul Vivek. The genomic basis of climate and host adaptation.

Degree: 2017, University of Melbourne

URL: http://hdl.handle.net/11343/177356

► Many species are currently threatened by the direct and indirect effects of anthropogenically driven climate change. The elevation of global temperatures and increase in variability… (more)

▼ Many species are currently threatened by the direct and indirect effects of anthropogenically driven climate change. The elevation of global temperatures and increase in variability in both temperature and precipitation pose a risk to biodiversity as species are pushed close to their thermal safety margins. Current predictions suggest a dramatic loss of species diversity and the contraction of geographical ranges of many species. Many ectothermic insects that cannot regulate their body temperature are likely to be threatened, particularly ecologically- restricted herbivorous insects that depend for on plants for food and that are often in phenological synchrony with their plant hosts. However, adaptive shifts in these species in response to host loss and climatic extremes may counter the effects of climate change to some extent. This highlights the importance of studying species-specific adaptation mechanisms including host interactions. This dissertation contributes to this overall aim by studying the genomic basis of climatic and host adaptation. I use Drosophila melanogaster as a model system at the intraspecific level, and Drosophila species from the repleta group as a model system for the comparative level. In assessing the genomic basis of host responses, I consider a much broader range of insect taxa. This dissertation begins with a study on the use of chromosome level sequencing of D. melanogaster populations from two ends of a thermal cline. I present genomic evidence for the role of the inversion 3R Payne in capturing alleles favourable to local climatic conditions in the non-inverted form, and therefore driving adaptation to climate change. The study further elucidates the impact of climatically important chromosomal inversions in driving higher linkage disequilibrium on the non-inverted form - potentially benefiting both karyotypes. In the second chapter, I develop a new pipeline, Orthonome, and tools for multi-species comparisons for prediction of orthologues and inparalogues with the highest accuracy and recall. Using Orthonome, I was able to identify a much greater level of conservation across Drosophilid lineages than earlier thought, amounting to nearly 33% better resolution than industry-accepted methods. I then use Orthonome in the third chapter to compare the genomes of 58 insect species – most of which are known to be agricultural pests. Testing across eight gene families, I present evidence for genomic patterns in only four gene families (P450s, CCEs, GSTs and ABCs) as being associated with polyphagy or particular host ranges. While three of them have been reported before, I find that ABC transporters present much stronger evidence than reflected in earlier studies, with feeding behaviour as well as host tissue displaying an effect on gene gain in more voracious pest species. Finally, in the last study, I use novel genomic data and evidence from the repleta group of drosophilids to carry out phylogenetically constrained analyses of genes potentially associated with host and thermal…

Subjects/Keywords: genomics; comparative genomics; population genetics/genomics; bioinformatics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rane, R. V. (2017). The genomic basis of climate and host adaptation. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/177356

Chicago Manual of Style (16^th Edition):

Rane, Rahul Vivek. “The genomic basis of climate and host adaptation.” 2017. Doctoral Dissertation, University of Melbourne. Accessed February 18, 2020. http://hdl.handle.net/11343/177356.

MLA Handbook (7^th Edition):

Rane, Rahul Vivek. “The genomic basis of climate and host adaptation.” 2017. Web. 18 Feb 2020.

Vancouver:

Rane RV. The genomic basis of climate and host adaptation. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/11343/177356.

Council of Science Editors:

Rane RV. The genomic basis of climate and host adaptation. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/177356

University of Helsinki

4. Andreevskaya, Margarita. Ecological fitness and interspecies interactions of food-spoilage-associated lactic acid bacteria: insights from the genome analyses and transcriptome profiles.

Degree: Department of Biosciences, Genetics division; University of Helsinki, Institute of Biotechnology; University of Helsinki, Department of Food Hygiene and Environmental Health, 2017, University of Helsinki

URL: http://hdl.handle.net/10138/170406

► Lactic acid bacteria (LAB) play a dual role in food manufacturing. While being indispensable for food fermentations and preservation, they are also involved in spoilage… (more)

▼ Lactic acid bacteria (LAB) play a dual role in food manufacturing. While being indispensable for food fermentations and preservation, they are also involved in spoilage of foods and beverages, and some food-borne LAB are pathogens. Particularly, they became the main spoilage organisms in the cold-stored modified atmosphere packaged (MAP) foods. LAB species composition and their relative abundances depend on the nature of food products and preservation technology. However, two LAB species, Leuconostoc gelidum and Lactococcus piscium, have frequently been predominating at the end of shelf life in a variety of packaged and refrigerated foods of animal and plant origin. Besides the predominant species, spoilage LAB communities contain less abundant and slower growing species, such as Lactobacillus oligofermentans, the role of which in food spoilage is unclear. Taking into account the increased popularity of MAP technology combined with cold storage for preservation of minimally processed fresh foods, the need to obtain more information on the metabolism, genomics, ecology and interactions of psychrotrophic food-spoilage-associated LAB is clear. In this thesis a genomic approach was used to study these LAB. In order to characterize spoilage community members, we sequenced and annotated genomes of Lc. piscium MKFS47 and Lb. oligofermentans LMG 22743T, both isolated from broiler meat, and seven strains of Le. gelidum, isolated from vegetable-based foods. The analysis of their gene contents and their comparison with gene repertoire of other close related species allowed us to predict putative factors that might facilitate their survival in their habitats and increase competitiveness in the spoilage microbial communities. No major differences in the gene contents of the vegetable and meat Le. gelidum strains were observed that would suggest niche-specificity, therefore, indicating that the absence of strain dissemination between vegetable- and meat-processing chains is a more likely factor responsible for the reported strain segregation between vegetable and meat-based products. Lc. piscium MKFS47 was identified as an efficient producer of buttery off-odors compounds from glucose under aerobic conditions, which is in agreement with the previous inoculation studies. Time course glucose catabolism-based transcriptome profiles revealed the presence of classical carbon catabolite repression mechanism for the regulation of carbohydrate catabolism, which was relieved along with decreasing concentration of glucose. During the same time, the shift from homolactic to heterolactic fermentation mode was observed. For Lb. oligofermentans, a pentose-preferring obligate heterofermentative LAB, the induction of efficient utilization of hexoses was confirmed indicating that it has flexible carbohydrate catabolism, which can be adjusted depending on the carbohydrate sources available in the environment. Unexpectedly, transcriptome responses of Lb. oligofermentans during growth on glucose and xylose were more alike than during…

Subjects/Keywords: bacterial genomics; bacterial genomics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Andreevskaya, M. (2017). Ecological fitness and interspecies interactions of food-spoilage-associated lactic acid bacteria: insights from the genome analyses and transcriptome profiles. (Doctoral Dissertation). University of Helsinki. Retrieved from http://hdl.handle.net/10138/170406

Chicago Manual of Style (16^th Edition):

Andreevskaya, Margarita. “Ecological fitness and interspecies interactions of food-spoilage-associated lactic acid bacteria: insights from the genome analyses and transcriptome profiles.” 2017. Doctoral Dissertation, University of Helsinki. Accessed February 18, 2020. http://hdl.handle.net/10138/170406.

MLA Handbook (7^th Edition):

Andreevskaya, Margarita. “Ecological fitness and interspecies interactions of food-spoilage-associated lactic acid bacteria: insights from the genome analyses and transcriptome profiles.” 2017. Web. 18 Feb 2020.

Vancouver:

Andreevskaya M. Ecological fitness and interspecies interactions of food-spoilage-associated lactic acid bacteria: insights from the genome analyses and transcriptome profiles. [Internet] [Doctoral dissertation]. University of Helsinki; 2017. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/10138/170406.

Council of Science Editors:

Andreevskaya M. Ecological fitness and interspecies interactions of food-spoilage-associated lactic acid bacteria: insights from the genome analyses and transcriptome profiles. [Doctoral Dissertation]. University of Helsinki; 2017. Available from: http://hdl.handle.net/10138/170406

Cornell University

5. Chen, Nancy. Genomics Of Population Decline In The Florida Scrub-Jay .

Degree: 2014, Cornell University

URL: http://hdl.handle.net/1813/38889

► Myriad species are experiencing declining numbers worldwide, yet many details of the eco-evolutionary responses to population decline remain poorly characterized in wild species. Rapidly shrinking… (more)

▼ Myriad species are experiencing declining numbers worldwide, yet many details of the eco-evolutionary responses to population decline remain poorly characterized in wild species. Rapidly shrinking populations experience loss of genetic diversity and increased homozygosity from changes in the balance of genetic drift, mutation, gene flow, selection, and inbreeding. Despite good theoretical knowledge of the impact of these factors on population genetics, thorough empirical evaluations in natural populations are scarce because they demand huge field and laboratory investments. Recent development of nextgeneration sequencing technologies now permits discovery and genotyping of large numbers of genetic markers in any species. Combining genomic data with long-term demographic and pedigree data from a natural population allows us to explore fundamental questions concerning the population genetic consequences of declining population size. Here, I describe two bioinformatics methods for analyzing genomic data and apply these methods to develop substantial genomic resources for one of the longest-studied endangered species in the world, the Florida Scrub-Jay (Aphelocoma coerulescens). One method identifies sequences specific to the heterogametic sex chromosome, and another uses pedigree information to improve single nucleotide polymorphism (SNP) discovery. A population of individually banded Florida Scrub-Jays at Archbold Biological Station has been studied for more than 43 years, providing an unparalleled model for research on the genomics of population decline. I geno- typed 3,578 individuals sampled through time at 15,416 genome-wide SNPs. To investigate the impact of regional population decline on our stable study population, I used 7,404 autosomal SNPs to calculate levels of heterozygosity and inbreeding. Decreasing immigration over time was correlated with an increasing mean inbreeding coefficient of the birth cohort, and inbreeding was correlated with higher rates of hatching failure. These results imply that despite the small and shrinking size of peripheral populations, their small but measurable genetic differentiation from the central population may give them a crucial role in maintaining genetic diversity. This study, which marks the beginning of a detailed longitudinal investigation of genomics in a wild animal population, underscores the vital importance of maintaining gene flow among remnant populations, for the Florida Scrub-Jay specifically, and for other declining species more broadly. Advisors/Committee Members: Harrison, Richard Gerald (committeeMember), Schat, Karel Antoni (committeeMember).

Subjects/Keywords: population genomics; bioinformatics; conservation genomics

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APA (6^th Edition):

Chen, N. (2014). Genomics Of Population Decline In The Florida Scrub-Jay . (Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/38889

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Nancy. “Genomics Of Population Decline In The Florida Scrub-Jay .” 2014. Thesis, Cornell University. Accessed February 18, 2020. http://hdl.handle.net/1813/38889.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Nancy. “Genomics Of Population Decline In The Florida Scrub-Jay .” 2014. Web. 18 Feb 2020.

Vancouver:

Chen N. Genomics Of Population Decline In The Florida Scrub-Jay . [Internet] [Thesis]. Cornell University; 2014. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/1813/38889.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen N. Genomics Of Population Decline In The Florida Scrub-Jay . [Thesis]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/38889

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

6. Sun, Guoying. A genetical genomics approach to genome scans for complex traits.

Degree: PhD, Statistics, 2008, University of Georgia

URL: http://purl.galileo.usg.edu/uga_etd/sun_guoying_200812_phd

► In the past few years, genetical genomics - the combination of gene expression and genetic marker data, have been used to conduct genome-wide survey of… (more)

Subjects/Keywords: Genetical Genomics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sun, G. (2008). A genetical genomics approach to genome scans for complex traits. (Doctoral Dissertation). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/sun_guoying_200812_phd

Chicago Manual of Style (16^th Edition):

Sun, Guoying. “A genetical genomics approach to genome scans for complex traits.” 2008. Doctoral Dissertation, University of Georgia. Accessed February 18, 2020. http://purl.galileo.usg.edu/uga_etd/sun_guoying_200812_phd.

MLA Handbook (7^th Edition):

Sun, Guoying. “A genetical genomics approach to genome scans for complex traits.” 2008. Web. 18 Feb 2020.

Vancouver:

Sun G. A genetical genomics approach to genome scans for complex traits. [Internet] [Doctoral dissertation]. University of Georgia; 2008. [cited 2020 Feb 18]. Available from: http://purl.galileo.usg.edu/uga_etd/sun_guoying_200812_phd.

Council of Science Editors:

Sun G. A genetical genomics approach to genome scans for complex traits. [Doctoral Dissertation]. University of Georgia; 2008. Available from: http://purl.galileo.usg.edu/uga_etd/sun_guoying_200812_phd

University of Georgia

7. Lu, Fang. A comparative genomic study of double-strand break repair in maize and rice.

Degree: MS, Genetics, 2009, University of Georgia

URL: http://purl.galileo.usg.edu/uga_etd/lu_fang_200905_ms

► Double-strand break (DSB) repair is essential for cell survival and for the maintenance of genome integrity. In this study, we utilized I-Sce I, an endonuclease… (more)

Subjects/Keywords: Comparative genomics

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APA (6^th Edition):

Lu, F. (2009). A comparative genomic study of double-strand break repair in maize and rice. (Masters Thesis). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/lu_fang_200905_ms

Chicago Manual of Style (16^th Edition):

Lu, Fang. “A comparative genomic study of double-strand break repair in maize and rice.” 2009. Masters Thesis, University of Georgia. Accessed February 18, 2020. http://purl.galileo.usg.edu/uga_etd/lu_fang_200905_ms.

MLA Handbook (7^th Edition):

Lu, Fang. “A comparative genomic study of double-strand break repair in maize and rice.” 2009. Web. 18 Feb 2020.

Vancouver:

Lu F. A comparative genomic study of double-strand break repair in maize and rice. [Internet] [Masters thesis]. University of Georgia; 2009. [cited 2020 Feb 18]. Available from: http://purl.galileo.usg.edu/uga_etd/lu_fang_200905_ms.

Council of Science Editors:

Lu F. A comparative genomic study of double-strand break repair in maize and rice. [Masters Thesis]. University of Georgia; 2009. Available from: http://purl.galileo.usg.edu/uga_etd/lu_fang_200905_ms

8. Wu, Hsin-Ta. Computational detection of driver mutations in cancer genomes.

Degree: PhD, Computer Science, 2016, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:674385/

► Cancer is caused largely by the accumulation of somatic mutations throughout an individual's life. Recent advances in next generation sequencing (NGS) enable measurement of somatic… (more)

▼ Cancer is caused largely by the accumulation of somatic mutations throughout an individual's life. Recent advances in next generation sequencing (NGS) enable measurement of somatic mutations in a cohort of samples. Cancer sequencing projects like The Cancer Genome Atlas (TCGA) have generated numerous somatic mutations in thousands of tumors. This thesis addresses two challenges. The first challenge is to distinguish the handful of driver mutations that are responsible for cancer development from the multitude of passenger mutations that play no role in cancer in a cohort of samples. The second challenge is to accurately identify larger genomic variants, also known as structural variants (SV). Although several computational methods have addressed this challenge using NGS technologies, they are limited by the underlying NGS data, resulting in a significant amount of SVs remaining undetectable, particularly in highly repetitive regions of the genome. To address the first challenge, we present two computational methods. First, we introduce a combinatorial approach for the problem of identifying independent and recurrent copy number aberrations, which are gains and losses of large genomic regions ranging in size from a few kilo-bases to whole chromosomes. We show that our method outperforms other methods on simulated data and performs well on TCGA cancer datasets. Second, we introduce a statistical model to identify combinations of driver mutations that are mutual exclusivity, a pattern expected for mutations in cancer pathways. Our model is more sensitive in detecting combinations of lower frequency mutations and outperforms other methods on simulated and real data. To address the second challenge, we present a method to identify SVs in a tumor more accurately by utilizing a new sequencing technology from 10X Genomics. 10X Genomics linked-reads technology uses barcodes to label reads originating from a longer DNA molecule, which enables the construction of synthetic long reads. Our method uses both signals from paired-end reads and synthetic long reads to identify SVs. We demonstrate that our method shows high sensitivity and specificity on simulated and real data. Together, these novel algorithms help address the challenge of characterizing and identifying driver mutations in cancer genomes. Advisors/Committee Members: Raphael, Benjamin (Director), Fairbrother, William (Reader), Upfal, Eli (Reader), Wu, Zhijin (Reader).

Subjects/Keywords: cancer genomics

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APA (6^th Edition):

Wu, H. (2016). Computational detection of driver mutations in cancer genomes. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:674385/

Chicago Manual of Style (16^th Edition):

Wu, Hsin-Ta. “Computational detection of driver mutations in cancer genomes.” 2016. Doctoral Dissertation, Brown University. Accessed February 18, 2020. https://repository.library.brown.edu/studio/item/bdr:674385/.

MLA Handbook (7^th Edition):

Wu, Hsin-Ta. “Computational detection of driver mutations in cancer genomes.” 2016. Web. 18 Feb 2020.

Vancouver:

Wu H. Computational detection of driver mutations in cancer genomes. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2020 Feb 18]. Available from: https://repository.library.brown.edu/studio/item/bdr:674385/.

Council of Science Editors:

Wu H. Computational detection of driver mutations in cancer genomes. [Doctoral Dissertation]. Brown University; 2016. Available from: https://repository.library.brown.edu/studio/item/bdr:674385/

9. Flight, Patrick A. Genetic signatures of natural selection and glaciation in the nearshore North Atlantic.

Degree: PhD, Ecological and Evolutionary Biology, 2012, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:297538/

► Identifying genetic targets of natural selection is a primary goal of evolutionary biology research. However, molecular signatures of natural selection must be interpreted with caution… (more)

▼ Identifying genetic targets of natural selection is a primary goal of evolutionary biology research. However, molecular signatures of natural selection must be interpreted with caution due to the fact that neutral demographic processes can confound signatures of selection in the genome. This thesis examines the neutral and selective genetic history of two nearshore marine species, the acorn barnacle, Semibalanus balanoides, and the estuarine fish, Fundulus heteroclitus. Both species are found on the Atlantic coast of North America, and currently occupy habitat that was profoundly influenced by glaciation throughout the Quarternary. In the case of S. balanoides, functional tests of selection at a candidate gene, Mannose-6-phosphate isomerase (Mpi), were combined with estimates of neutral demographic history using mtDNA, microsatellite data, and whole-genome, second-generation sequencing. The Mpi locus was also sequenced directly to test for selection. There was evidence for functional differences at Mpi based on genotype-dependent size phenotypes. As predicted, there were observable effects of glaciation on populations from the western and eastern North Atlantic, with less genetic variation observed in the western North Atlantic populations. The Mpi locus had a significantly elevated level of Tajima’s D, consistent with balancing selection. Through second-generation sequencing the largest currently available dataset for a cirripede was created, with approximately 41x coverage of the genome of S. balanoides recovered. In F. heteroclitus a glacial hybrid population was sampled to study the effects of sex and mitochondrial genotype on fitness and gene expression under hypoxia. Gene expression was measured using microarrays and RT-PCR. A highly significant effect of sex on hypoxia tolerance was discovered, but mitochondrial genotype effects were not significant. Hundreds of genes were differentially regulated by sex and hypoxia. Mitochondrial genotypes had minimal effects on gene expression, but several important candidate genes were discovered. The final chapter of the dissertation used phylogenetic comparative methods to examine endangerment status and genetic diversity in tetrapods. Advisors/Committee Members: Rand, David (Director), Bertness, Mark (Reader), Weinreich, Daniel (Reader), Simmons, Sheri (Reader), Palumbi, Stephen (Reader).

Subjects/Keywords: Ecological Genomics

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APA (6^th Edition):

Flight, P. A. (2012). Genetic signatures of natural selection and glaciation in the nearshore North Atlantic. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297538/

Chicago Manual of Style (16^th Edition):

Flight, Patrick A. “Genetic signatures of natural selection and glaciation in the nearshore North Atlantic.” 2012. Doctoral Dissertation, Brown University. Accessed February 18, 2020. https://repository.library.brown.edu/studio/item/bdr:297538/.

MLA Handbook (7^th Edition):

Flight, Patrick A. “Genetic signatures of natural selection and glaciation in the nearshore North Atlantic.” 2012. Web. 18 Feb 2020.

Vancouver:

Flight PA. Genetic signatures of natural selection and glaciation in the nearshore North Atlantic. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2020 Feb 18]. Available from: https://repository.library.brown.edu/studio/item/bdr:297538/.

Council of Science Editors:

Flight PA. Genetic signatures of natural selection and glaciation in the nearshore North Atlantic. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297538/

10. Leiserson, Mark DM. Methods for Identifying Combinations of Driver Mutations in Cancer.

Degree: PhD, Computer Science, 2016, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:674297/

► Recent improvements in DNA sequencing technology have opened new paths towards understanding cancer biology and designing personalized cancer treatments. Cancer is caused in part by… (more)

▼ Recent improvements in DNA sequencing technology have opened new paths towards understanding cancer biology and designing personalized cancer treatments. Cancer is caused in part by somatic mutations to the DNA of healthy cells that can be identified with DNA sequencing technology. A major challenge in analyzing the mutations in cancer is distinguishing the handful of driver mutations that cause cancer from the multitude of passenger mutations that play no role in cancer. In part to address this challenge, consortia such as The Cancer Genome Atlas (TCGA) have generated massive catalogues of somatic mutations in thousands of tumors. The new wealth of mutation data has shown that identifying driver mutations is a difficult computational problem. Many driver mutations are rare, even in these large tumor cohorts, because different combinations of mutations cause cancer in different patients, even those of the same cancer (sub)type. Part of the reason for this phenomenon is that driver mutations target key genetic pathways that perform vital cell functions. Each pathway consists of a set of interacting genes, and can be perturbed in numerous ways. Therefore, we have developed computational methods to search for combinations of driver mutations targeting pathways. We describe several methods for identifying combinations of putative driver mutations. We first present two methods for identifying combinations of mutations that are mutually exclusive in a cohort of tumors, a pattern expected for genetic pathways. We then present an algorithm to identify significant clusters of mutations in an interaction network. We show that these algorithms outperform previous methods on simulated and real mutation data from TCGA, and identify potentially novel combinations of mutations. We also describe the Mutation Annotation and Genome Interpretation (MAGI) web application, which displays interactive visualizations as well as crowd-sourced and text-mined mutation annotations in order to help prioritize likely driver mutations. These methods contribute towards overcoming the computational challenge of identifying driver mutations in cancer sequencing data. Advisors/Committee Members: Raphael, Benjamin (Director), Laidlaw, David (Reader), Ramachandran, Sohini (Reader), Park, Peter (Reader).

Subjects/Keywords: cancer genomics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Leiserson, M. D. (2016). Methods for Identifying Combinations of Driver Mutations in Cancer. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:674297/

Chicago Manual of Style (16^th Edition):

Leiserson, Mark DM. “Methods for Identifying Combinations of Driver Mutations in Cancer.” 2016. Doctoral Dissertation, Brown University. Accessed February 18, 2020. https://repository.library.brown.edu/studio/item/bdr:674297/.

MLA Handbook (7^th Edition):

Leiserson, Mark DM. “Methods for Identifying Combinations of Driver Mutations in Cancer.” 2016. Web. 18 Feb 2020.

Vancouver:

Leiserson MD. Methods for Identifying Combinations of Driver Mutations in Cancer. [Internet] [Doctoral dissertation]. Brown University; 2016. [cited 2020 Feb 18]. Available from: https://repository.library.brown.edu/studio/item/bdr:674297/.

Council of Science Editors:

Leiserson MD. Methods for Identifying Combinations of Driver Mutations in Cancer. [Doctoral Dissertation]. Brown University; 2016. Available from: https://repository.library.brown.edu/studio/item/bdr:674297/

University of Illinois – Chicago

11. Aurisano, Jillian M. Bacterial Gene Neighborhood Investigation Environment: A Scalable Genome Visualization for Big Displays.

Degree: 2014, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19160

► In the past decade, genome sequencing costs have decreased faster than Moore's Law, resulting in a rapid increase in the volume of genomic data. This… (more)

Subjects/Keywords: Visualization; Genomics

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APA (6^th Edition):

Aurisano, J. M. (2014). Bacterial Gene Neighborhood Investigation Environment: A Scalable Genome Visualization for Big Displays. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Aurisano, Jillian M. “Bacterial Gene Neighborhood Investigation Environment: A Scalable Genome Visualization for Big Displays.” 2014. Thesis, University of Illinois – Chicago. Accessed February 18, 2020. http://hdl.handle.net/10027/19160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Aurisano, Jillian M. “Bacterial Gene Neighborhood Investigation Environment: A Scalable Genome Visualization for Big Displays.” 2014. Web. 18 Feb 2020.

Vancouver:

Aurisano JM. Bacterial Gene Neighborhood Investigation Environment: A Scalable Genome Visualization for Big Displays. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/10027/19160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Aurisano JM. Bacterial Gene Neighborhood Investigation Environment: A Scalable Genome Visualization for Big Displays. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/19160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Cornell University

12. Qu, Xian. Genetic And Genomic Controls Of Cell Size Patterning In Arabidopsis Sepals .

Degree: 2015, Cornell University

URL: http://hdl.handle.net/1813/41172

► Growth and division are the two most important processes in plant organogenesis. Cell size results from the dynamic combination of these two processes. Hence studying… (more)

Subjects/Keywords: Development; Genomics

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APA (6^th Edition):

Qu, X. (2015). Genetic And Genomic Controls Of Cell Size Patterning In Arabidopsis Sepals . (Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/41172

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Qu, Xian. “Genetic And Genomic Controls Of Cell Size Patterning In Arabidopsis Sepals .” 2015. Thesis, Cornell University. Accessed February 18, 2020. http://hdl.handle.net/1813/41172.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Qu, Xian. “Genetic And Genomic Controls Of Cell Size Patterning In Arabidopsis Sepals .” 2015. Web. 18 Feb 2020.

Vancouver:

Qu X. Genetic And Genomic Controls Of Cell Size Patterning In Arabidopsis Sepals . [Internet] [Thesis]. Cornell University; 2015. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/1813/41172.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Qu X. Genetic And Genomic Controls Of Cell Size Patterning In Arabidopsis Sepals . [Thesis]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/41172

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Minnesota

13. Nelson, Justin. Genomic Approaches for Characterizing How Chemicals Act on Cells.

Degree: PhD, Biomedical Informatics and Computational Biology, 2019, University of Minnesota

URL: http://hdl.handle.net/11299/203573

► The realization of precision medicine demands new therapies to probe an increasingly diverse set of molecular targets. Unfortunately, existing drug development paradigms narrowly focus on… (more)

▼ The realization of precision medicine demands new therapies to probe an increasingly diverse set of molecular targets. Unfortunately, existing drug development paradigms narrowly focus on single targets and are ill-equipped to efficiently discover collections of compounds that could address the need for individualized treatments. This challenge necessitates the development of new methods for systematically characterizing how chemicals act on cells. The completion of a comprehensive genetic interaction network in Saccharomyces cerevisiae presents a unique opportunity to develop new strategies for discovering new molecular probes. Genetic interactions have been used successfully to characterize the mode-of-action of compounds. However, to date, these methods have not been scaled to enable cost-effective screens of large compound libraries, which limits their practical use in a drug discovery context. This dissertation will describe my development of computational tools for integrating chemical-genetic and genetic interactions in S. cerevisiae to characterize compounds’ mode-of-action. With our experimental collaborators, we scaled this approach to generate and interpret chemical-genetic interaction profiles for more than 10,000 compounds. To facilitate broad use of these data and methods, I built a web portal, called MOSAIC, for visualization and analysis of our chemical genetic profiles. I also describe an application of this chemical genomics technology to discover new therapeutic leads for a rare human disease, called facioscapulohumeral muscular dystrophy (FSHD). I developed a cross-species approach that combines a murine phenotypic assay with yeast chemical-genetic profiling to characterize the mechanism of compounds protective against toxicity associated with this disease and discover new leads that target this mechanism. Finally, my dissertation extends beyond the study of single chemical-genetic perturbations to address the question of how pairwise combinations of genetic perturbations are affected across diverse chemical environments. We screened ~30,000 double mutants across 14 chemical stresses and characterized the extent to which genetic interactions are dependent on the chemical stress. We suggest a strategy for efficient selection of environments and genes that can be applied to study condition-dependent genetic interactions in other systems.

Subjects/Keywords: Chemical Genomics

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APA (6^th Edition):

Nelson, J. (2019). Genomic Approaches for Characterizing How Chemicals Act on Cells. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/203573

Chicago Manual of Style (16^th Edition):

Nelson, Justin. “Genomic Approaches for Characterizing How Chemicals Act on Cells.” 2019. Doctoral Dissertation, University of Minnesota. Accessed February 18, 2020. http://hdl.handle.net/11299/203573.

MLA Handbook (7^th Edition):

Nelson, Justin. “Genomic Approaches for Characterizing How Chemicals Act on Cells.” 2019. Web. 18 Feb 2020.

Vancouver:

Nelson J. Genomic Approaches for Characterizing How Chemicals Act on Cells. [Internet] [Doctoral dissertation]. University of Minnesota; 2019. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/11299/203573.

Council of Science Editors:

Nelson J. Genomic Approaches for Characterizing How Chemicals Act on Cells. [Doctoral Dissertation]. University of Minnesota; 2019. Available from: http://hdl.handle.net/11299/203573

Harvard University

14. Gallagher, C. Scott. Genetic, Functional, and Epidemiologic Analyses of Genomic Variants in Uterine Leiomyomata.

Degree: PhD, 2018, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129130

►

Uterine leiomyomata (UL), commonly known as fibroids, are one of the primary causes of morbidity in reproductive-aged women. Epidemiologic analyses, including twin studies, familial aggregation,… (more)

▼

Uterine leiomyomata (UL), commonly known as fibroids, are one of the primary causes of morbidity in reproductive-aged women. Epidemiologic analyses, including twin studies, familial aggregation, and racial biases in disease prevalence and morbidity, suggest heritable factors influence disease risk. Previous genetic association analyses in Japanese women reported three independent loci at 10q24.33, 11p15.5, and 22q13.1; genome-wide linkage and association analyses in European women identified a genomic region encompassing FASN at 17q25.3; and, a genome-wide association study (GWAS) in African American women associated a separate region at 22q13.1 with UL. To replicate and identify additional risk variants, we assembled FibroGENE – a consortium of conventional, population-based and direct-to-consumer cohorts. Discovery-phase meta-analysis of 244,324 European women replicated the three previously associated loci in Japanese women and identified 21 novel genomic regions. Of the 24 loci in total, 17 were replicated (p < 2.08e-3) in an independent, direct-to-consumer cohort of 58,655 European women obtained through 23andMe’s Research Portal. Meta-analysis across all five cohorts of 302,979 European women revealed an additional six discovery loci. Estrogen receptor alpha (ESR1) and forkhead box protein O1 (FOXO1) were located in two candidate regions associated with UL in our analyses at 6q25.2 and 13q14.11, respectively. FOXO1 is a well-characterized tumor suppressor and hormone-regulated transcription factor that interacts with ESR1 in the estrogen-signaling pathway. We observed significant, 2.18-fold greater nuclear FOXO1 levels in UL patient samples compared to myometrial control tissue in an immunohistochemistry-based assay. Interestingly, four regions that were identified and replicated in our FibroGENE analysis were also previously associated with endometriosis – another estrogen-dependent disease affecting uterine tissue. Epidemiologic meta-analysis of multivariate-adjusted risk estimates from the Nurses’ Health Study II and Women’s Health Study revealed women with a history of endometriosis had greater odds of UL when compared to women with no previous diagnosis of endometriosis. Here, we report the identification of a previously undocumented genetic overlap between endometriosis and UL and further underscore the relationship by formal epidemiologic quantification of the comorbidity of these two highly common gynecologic diseases.

Medical Sciences

Advisors/Committee Members: Kucherlapati, Raju (advisor), Hirschhorn, Joel (committee member), Anchan, Raymond (committee member), Yea, Amy (committee member).

Subjects/Keywords: Leiomyomata; Genomics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gallagher, C. S. (2018). Genetic, Functional, and Epidemiologic Analyses of Genomic Variants in Uterine Leiomyomata. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129130

Chicago Manual of Style (16^th Edition):

Gallagher, C Scott. “Genetic, Functional, and Epidemiologic Analyses of Genomic Variants in Uterine Leiomyomata.” 2018. Doctoral Dissertation, Harvard University. Accessed February 18, 2020. http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129130.

MLA Handbook (7^th Edition):

Gallagher, C Scott. “Genetic, Functional, and Epidemiologic Analyses of Genomic Variants in Uterine Leiomyomata.” 2018. Web. 18 Feb 2020.

Vancouver:

Gallagher CS. Genetic, Functional, and Epidemiologic Analyses of Genomic Variants in Uterine Leiomyomata. [Internet] [Doctoral dissertation]. Harvard University; 2018. [cited 2020 Feb 18]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129130.

Council of Science Editors:

Gallagher CS. Genetic, Functional, and Epidemiologic Analyses of Genomic Variants in Uterine Leiomyomata. [Doctoral Dissertation]. Harvard University; 2018. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129130

University of Oxford

15. Karami Nejad Ranjbar, Mohammad. On the origin, progression, and evolution of ovarian cancer.

Degree: PhD, 2018, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:d6e7885c-d245-41d1-a5ea-2f8bf7e66321 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.770636

► High-grade serous ovarian cancer (HGSOC) is amongst the deadliest of cancers. Despite decades of research on this disease, the exact mechanisms through which this carcinoma… (more)

▼ High-grade serous ovarian cancer (HGSOC) is amongst the deadliest of cancers. Despite decades of research on this disease, the exact mechanisms through which this carcinoma initiates, spreads, and relapses remain unclear. I believe the main reason behind this discrepancy between importance and available knowledge roots in the fact that currently available genomics methods are not sensitive enough for accurate study of limited amount of clinical materials. To address this issue, I optimised a novel library preparation protocol called DigiPico to generate reliable next generation sequencing data from picogram quantities of DNA that can be obtained from 10-20 human cells. Moreover, I implemented DigiTitan and MutLX analysis algorithms to identify clone-specific copy number alterations and small nucleotide variations from DigiPico data. Validating MutLX algorithm using experimental and simulated data I demonstrated that DigiPico/MutLX is a uniquely sensitive, accurate, and reliable method for analysis of micro-heterogeneity in solid tumours. Next, using DigiPico, I conducted the first accurate case study of genetic micro-heterogeneity on a collection of pre-chemotherapy tumour islets and post-chemotherapy microscopic residual disease (MRD) samples from one HGSOC patient. Analysing the results using DigiTitan and MutLX, firstly, I introduced tumour heterogeneity and genetic diversity as a hallmark of HGSOC. Secondly, based on new observations from this study, I challenged a pre-existing notion that mutations in TP53 gene are responsible for the initiation of HGSOC. I proposed that mutations in the regulatory regions that adversely affect the DNA repair machinery which can lead to subsequent large-scale genomic alterations precede the loss of TP53 function in the tumorigenesis pathway of HGSOC. Thirdly, comparing the somatic mutation load of pre-chemotherapy, MRD and recurrent tumours, I demonstrated that MRD harbours the least number of somatic mutations. Thereby, I hypothesized that MRD is likely to be composed of stem cell-like tumour cells that have survived the chemotherapy therefore suggesting that MRD is likely be the recurrence precursor. Lastly, I propose experimental approaches that are required to effectively validate or nullify these hypotheses.

Subjects/Keywords: Genomics; Cancer

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APA (6^th Edition):

Karami Nejad Ranjbar, M. (2018). On the origin, progression, and evolution of ovarian cancer. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:d6e7885c-d245-41d1-a5ea-2f8bf7e66321 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.770636

Chicago Manual of Style (16^th Edition):

Karami Nejad Ranjbar, Mohammad. “On the origin, progression, and evolution of ovarian cancer.” 2018. Doctoral Dissertation, University of Oxford. Accessed February 18, 2020. http://ora.ox.ac.uk/objects/uuid:d6e7885c-d245-41d1-a5ea-2f8bf7e66321 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.770636.

MLA Handbook (7^th Edition):

Karami Nejad Ranjbar, Mohammad. “On the origin, progression, and evolution of ovarian cancer.” 2018. Web. 18 Feb 2020.

Vancouver:

Karami Nejad Ranjbar M. On the origin, progression, and evolution of ovarian cancer. [Internet] [Doctoral dissertation]. University of Oxford; 2018. [cited 2020 Feb 18]. Available from: http://ora.ox.ac.uk/objects/uuid:d6e7885c-d245-41d1-a5ea-2f8bf7e66321 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.770636.

Council of Science Editors:

Karami Nejad Ranjbar M. On the origin, progression, and evolution of ovarian cancer. [Doctoral Dissertation]. University of Oxford; 2018. Available from: http://ora.ox.ac.uk/objects/uuid:d6e7885c-d245-41d1-a5ea-2f8bf7e66321 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.770636

Wilfrid Laurier University

16. Vey, Gregory Detlev Alexander. Inference, Orthology, and Inundation: Addressing Current Challenges in the Field of Metagenomics.

Degree: 2009, Wilfrid Laurier University

URL: https://scholars.wlu.ca/etd/954

► The vast increase in the number of sequenced genomes has irreversibly changed the landscape of the biological sciences and has spawned the current post-genomic era… (more)

▼ The vast increase in the number of sequenced genomes has irreversibly changed the landscape of the biological sciences and has spawned the current post-genomic era of research. Genomic data have illuminated many adaptation and survival strategies between species and their habitats. Moreover, the analysis of prokaryotic genomic sequences is indispensible for understanding the mechanisms of bacterial pathogens and for subsequently developing effective diagnostics, drugs, and vaccines. Computational strategies for the annotation of genomic sequences are driven by the inference of function from reference genomes. However, the effectiveness of such methods is bounded by the fractional diversity of known genomes. Although metagenomes can reconcile this limitation by offering access to previously intangible organisms, harnessing metagenomic data comes with its own collection of challenges. Since the sequenced environmental fragments of metagenomes do not equate to discrete and fully intact genomes, this prevents the conventional establishment of orthologous relationships that are required for functional inference. Furthermore, the current surge in metagenomic data sets requires the development of compression strategies that can effectively accommodate large data sets that are comprised of multiple sequences and a greater proportion of auxiliary data, such as sequence headers. While modern hardware can provide vast amounts of inexpensive storage for biological databases, the compression of nucleotide sequence data is still of paramount importance in order to facilitate fast search and retrieval operations through a reduction in disk traffic. To address the issues of inference and orthology a novel protocol was developed for the prediction of functional interactions that supports data sources that lack information about orthologous relationships. To address the issue of database inundation, a compression protocol was designed that can differentiate between sequence data and auxiliary data, thereby offering reconciliation between sequence specific and general-purpose compression strategies. By resolving these and other challenges, it becomes possible to extend the potential utility of the emerging field of metagenomics.

Subjects/Keywords: Genomics

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APA (6^th Edition):

Vey, G. D. A. (2009). Inference, Orthology, and Inundation: Addressing Current Challenges in the Field of Metagenomics. (Thesis). Wilfrid Laurier University. Retrieved from https://scholars.wlu.ca/etd/954

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vey, Gregory Detlev Alexander. “Inference, Orthology, and Inundation: Addressing Current Challenges in the Field of Metagenomics.” 2009. Thesis, Wilfrid Laurier University. Accessed February 18, 2020. https://scholars.wlu.ca/etd/954.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vey, Gregory Detlev Alexander. “Inference, Orthology, and Inundation: Addressing Current Challenges in the Field of Metagenomics.” 2009. Web. 18 Feb 2020.

Vancouver:

Vey GDA. Inference, Orthology, and Inundation: Addressing Current Challenges in the Field of Metagenomics. [Internet] [Thesis]. Wilfrid Laurier University; 2009. [cited 2020 Feb 18]. Available from: https://scholars.wlu.ca/etd/954.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vey GDA. Inference, Orthology, and Inundation: Addressing Current Challenges in the Field of Metagenomics. [Thesis]. Wilfrid Laurier University; 2009. Available from: https://scholars.wlu.ca/etd/954

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Wilfrid Laurier University

17. Masella, Andre. Insights into Genome Functional Organisation through the Analysis of Interaction Networks.

Degree: 2010, Wilfrid Laurier University

URL: https://scholars.wlu.ca/etd/1024

► Using computational techniques to identify orthology and operon structure, it is possible to find functional interactions between genes, which, together, define the genetic interactome. These… (more)

Subjects/Keywords: Genomics

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APA (6^th Edition):

Masella, A. (2010). Insights into Genome Functional Organisation through the Analysis of Interaction Networks. (Thesis). Wilfrid Laurier University. Retrieved from https://scholars.wlu.ca/etd/1024

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Masella, Andre. “Insights into Genome Functional Organisation through the Analysis of Interaction Networks.” 2010. Thesis, Wilfrid Laurier University. Accessed February 18, 2020. https://scholars.wlu.ca/etd/1024.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Masella, Andre. “Insights into Genome Functional Organisation through the Analysis of Interaction Networks.” 2010. Web. 18 Feb 2020.

Vancouver:

Masella A. Insights into Genome Functional Organisation through the Analysis of Interaction Networks. [Internet] [Thesis]. Wilfrid Laurier University; 2010. [cited 2020 Feb 18]. Available from: https://scholars.wlu.ca/etd/1024.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Masella A. Insights into Genome Functional Organisation through the Analysis of Interaction Networks. [Thesis]. Wilfrid Laurier University; 2010. Available from: https://scholars.wlu.ca/etd/1024

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

18. DALY, KEVIN. Ancient Goat Genomics: Structure, Selection, and Admixture.

Degree: School of Genetics & Microbiology. Discipline of Genetics, 2019, Trinity College Dublin

URL: http://hdl.handle.net/2262/86163

► The wild bezoar Capra aegagrus was brought under human control c. 8,000 BC, leading to the domestic goat Capra hircus. This livestock species remains in… (more)

▼ The wild bezoar Capra aegagrus was brought under human control c. 8,000 BC, leading to the domestic goat Capra hircus. This livestock species remains in use 10,000 years later, and is of particular importance to communities in marginal and developing regions. Despite this long and significant shared history, our knowledge of the process of goat domestication is poor and reliant on modern populations. Using genomic data derived from over 80 ancient Capra remains from southwest Asia and Europe, the patterns of genetic diversity which characterize domestic goat through time are described. Neolithic goat populations appear to share a common ancestor, supporting a single domestication process. However, strong regional differentiation and direct tests of admixture indicate localized gene flow from the wild, contributing to goat genetic diversity in both ancient and modern populations and suggesting a domestication process featuring substantial interaction with diverse wild groups. A significant genetic turnover following the Neolithic time period is observed, most strikingly in the mitochondrial gene pool but also with nuclear genome evidence, supporting a homogenization of southwest Asian goat populations. A FST outlier scan identified several regions strongly differentiated in Neolithic goat populations, including regions close or overlapping the pigmentation genes KIT and KITLG and providing evidence for the early selection by farmers for prefered phenotypes. Genomic data from 14 historic Capra samples provides context to the genus, and suggests gene flow between domestic goat other Capra species. In addition, an Epipaleolithic genome from Direkli Cave, southern Turkey, is shown to have high affinity with the Caucasian Tur, suggesting divergent populations of Capra exist in the wild that have yet to be described. Finally, genomic data from a further 26 samples are suggestive of additional complexity in early goat herding, but indicate the geographic regions which must be studied to address unresolved questions regarding the history of domestic goat. Advisors/Committee Members: Bradley, Daniel.

Subjects/Keywords: Genomics; Goat

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

DALY, K. (2019). Ancient Goat Genomics: Structure, Selection, and Admixture. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/86163

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

DALY, KEVIN. “Ancient Goat Genomics: Structure, Selection, and Admixture.” 2019. Thesis, Trinity College Dublin. Accessed February 18, 2020. http://hdl.handle.net/2262/86163.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

DALY, KEVIN. “Ancient Goat Genomics: Structure, Selection, and Admixture.” 2019. Web. 18 Feb 2020.

Vancouver:

DALY K. Ancient Goat Genomics: Structure, Selection, and Admixture. [Internet] [Thesis]. Trinity College Dublin; 2019. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/2262/86163.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

DALY K. Ancient Goat Genomics: Structure, Selection, and Admixture. [Thesis]. Trinity College Dublin; 2019. Available from: http://hdl.handle.net/2262/86163

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Tech

19. Dang, Ha Xuan. Mold Allergomics: Comparative and Machine Learning Approaches.

Degree: PhD, Animal and Poultry Sciences, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/64205

► Fungi are one of the major organisms that cause allergic disease in human. A number of proteins from fungi have been found to be allergenic… (more)

▼ Fungi are one of the major organisms that cause allergic disease in human. A number of proteins from fungi have been found to be allergenic or possess immunostimulatory properties. Identifying and characterizing allergens from fungal genomes will help facilitate our understanding of the mechanism underlying host-pathogen interactions in allergic diseases. Currently, there is a lack of tools that allow us to rapidly and accurately predict allergens from whole genomes. In the context of whole genome annotation, allergens are rare compared to non-allergens and thus the data is considered highly skewed. In order to achieve a confident set of predicted allergens from a genome, false positive rates must be lowered. Current allergen prediction tools often produce many false positives when applied to large-scale data set such as whole genomes, and thus lower the precision. Moreover, the most accurate tools are relatively slow because they use sequence alignment to construct feature vectors for allergen classifiers. This dissertation presents computational approaches in characterizing the allergen repertoire in fungal genomes as part of the whole genome studies of Alternaria, an important allergenic/opportunistic human pathogenic fungus and necrotrophic plant parasite. In these studies, the genomes of multiple Alternaria species were characterized for the first time. Functional elements (e.g. genes, proteins) were first identified and annotated from these genomes using computational tools. Protein annotation and comparative genomics approaches revealed the link between Alternaria genotypes and its prolific saprophytic lifestyle that provides at least a partial explanation for the development of pathological relationships between Alternaria and humans. A machine learning based tool (Allerdictor) was developed to address the neglected problem of allergen prediction in highly skewed large-scale data sets. Allerdictor exhibited high precision over high recall at fast speed and thus it is a more practical tool for large-scale allergen annotation compared with existing tools. Allerdictor was then used together with a comparative genomics approach to survey the allergen repertoire of known allergenic fungi. We predicted a number of mold allergens that have not been experimentally characterized. These predicted allergens are potential candidates for further experimental and clinical validation. Our approaches will not only facilitate the study of allergens in the increasing number of sequenced fungal genomes but also will be useful for allergen annotation in other species and rapid prescreening of synthesized sequences for potential allergens. Advisors/Committee Members: Lawrence, Christopher B. (committeechair), Tyler, Brett M. (committee member), Heath, Lenwood S. (committee member), Murali, T M. (committee member).

Subjects/Keywords: Fungal genomics; comparative genomics; allergy; allergen prediction

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APA (6^th Edition):

Dang, H. X. (2014). Mold Allergomics: Comparative and Machine Learning Approaches. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/64205

Chicago Manual of Style (16^th Edition):

Dang, Ha Xuan. “Mold Allergomics: Comparative and Machine Learning Approaches.” 2014. Doctoral Dissertation, Virginia Tech. Accessed February 18, 2020. http://hdl.handle.net/10919/64205.

MLA Handbook (7^th Edition):

Dang, Ha Xuan. “Mold Allergomics: Comparative and Machine Learning Approaches.” 2014. Web. 18 Feb 2020.

Vancouver:

Dang HX. Mold Allergomics: Comparative and Machine Learning Approaches. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/10919/64205.

Council of Science Editors:

Dang HX. Mold Allergomics: Comparative and Machine Learning Approaches. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/64205

Virginia Tech

20. Kang, Lin. Comparative Genomics Insights into Speciation and Evolution of Hawaiian Drosophila.

Degree: PhD, Animal and Poultry Sciences, 2017, Virginia Tech

URL: http://hdl.handle.net/10919/85467

► Speciation and adaptation have always been of great interest to biologists. The Hawaiian archipelago provides a natural arena for understanding adaptive radiation and speciation, and… (more)

Subjects/Keywords: Genomics; Comparative genomics; Drosophila; Evolution; Adaptation

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APA (6^th Edition):

Kang, L. (2017). Comparative Genomics Insights into Speciation and Evolution of Hawaiian Drosophila. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/85467

Chicago Manual of Style (16^th Edition):

Kang, Lin. “Comparative Genomics Insights into Speciation and Evolution of Hawaiian Drosophila.” 2017. Doctoral Dissertation, Virginia Tech. Accessed February 18, 2020. http://hdl.handle.net/10919/85467.

MLA Handbook (7^th Edition):

Kang, Lin. “Comparative Genomics Insights into Speciation and Evolution of Hawaiian Drosophila.” 2017. Web. 18 Feb 2020.

Vancouver:

Kang L. Comparative Genomics Insights into Speciation and Evolution of Hawaiian Drosophila. [Internet] [Doctoral dissertation]. Virginia Tech; 2017. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/10919/85467.

Council of Science Editors:

Kang L. Comparative Genomics Insights into Speciation and Evolution of Hawaiian Drosophila. [Doctoral Dissertation]. Virginia Tech; 2017. Available from: http://hdl.handle.net/10919/85467

University of Utah

21. Seipp, Michael Todd. Genotyping by High-Resolution Amplicon Melting.

Degree: MS;, Pathology;, 2010, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1243/rec/527

► Genotyping by high-resolution amplicon melting is a simple method using only PCR primers and double-stranded DNA binding dyes. Heterozygous genotypes are easily assigned based on… (more)

Subjects/Keywords: Genomics; Gene Amplification

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APA (6^th Edition):

Seipp, M. T. (2010). Genotyping by High-Resolution Amplicon Melting. (Masters Thesis). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1243/rec/527

Chicago Manual of Style (16^th Edition):

Seipp, Michael Todd. “Genotyping by High-Resolution Amplicon Melting.” 2010. Masters Thesis, University of Utah. Accessed February 18, 2020. http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1243/rec/527.

MLA Handbook (7^th Edition):

Seipp, Michael Todd. “Genotyping by High-Resolution Amplicon Melting.” 2010. Web. 18 Feb 2020.

Vancouver:

Seipp MT. Genotyping by High-Resolution Amplicon Melting. [Internet] [Masters thesis]. University of Utah; 2010. [cited 2020 Feb 18]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1243/rec/527.

Council of Science Editors:

Seipp MT. Genotyping by High-Resolution Amplicon Melting. [Masters Thesis]. University of Utah; 2010. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1243/rec/527

Texas A&M University

22. Fisher, Colleen 1988-. Diversity and Evolution of the Bovine and Equine Toll-Like Receptor Gene Family: Applications to Animal Disease.

Degree: 2012, Texas A&M University

URL: http://hdl.handle.net/1969.1/148065

► Genes modulating innate immunity in mammals are generally considered the first line of defense with respect to invading pathogens and therefore it has become important… (more)

▼ Genes modulating innate immunity in mammals are generally considered the first line of defense with respect to invading pathogens and therefore it has become important to characterize naturally occurring genetic variation, and subsequently determine whether this variation is likely to be benign, beneficial, or detrimental to the host. Relevant to this study, the mammalian Toll-like receptor proteins (TLR), encoded by members of the TLR gene family, have the capacity to recognize a wide variety of pathogen ligands, and mutations within these genes have been shown to influence disease susceptibility or resistance within mammalian species. Two studies which sought to determine the frequency and distribution of naturally occurring genetic variation within the bovine and equine TLR genes revealed a large number of discrete point mutations, which were subsequently used to reconstruct haplotypes for each investigated gene across a large number of samples. Detailed analyses of haplotypes provided evidence for extensive haplotype sharing among specialized breeds, subspecies, and even divergent species. Classical and new tests of selection provided evidence for significant deviations from a strictly neutral model of molecular evolution for both cattle as well as equids, with some of the same TLR genes deviating from a strictly neutral model among divergent species. As a first step toward determining whether naturally occurring bovine TLR variation is likely to be benign, beneficial, or detrimental, we tested validated variation from bovine TLR genes capable of recognizing components of Mycobacteria for associations with Mycobacterium avium subspecies paratuberculosis (MAP) infection in dairy cattle, and found several SNPs that were nominally associated with disease status, thereby providing evidence for small-effect loci potentially influencing risk for differential susceptibility to Johne's disease. Advisors/Committee Members: Seabury, Christopher M (advisor), Criscitiello, Michael (committee member), Murphy, William (committee member).

Subjects/Keywords: Johne's Disease; Toll-like receptor; TLR; Horse Genomics; Cattle Genomics; Equine Genomics; Bovine Genomics

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APA (6^th Edition):

Fisher, C. 1. (2012). Diversity and Evolution of the Bovine and Equine Toll-Like Receptor Gene Family: Applications to Animal Disease. (Thesis). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/148065

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fisher, Colleen 1988-. “Diversity and Evolution of the Bovine and Equine Toll-Like Receptor Gene Family: Applications to Animal Disease.” 2012. Thesis, Texas A&M University. Accessed February 18, 2020. http://hdl.handle.net/1969.1/148065.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fisher, Colleen 1988-. “Diversity and Evolution of the Bovine and Equine Toll-Like Receptor Gene Family: Applications to Animal Disease.” 2012. Web. 18 Feb 2020.

Vancouver:

Fisher C1. Diversity and Evolution of the Bovine and Equine Toll-Like Receptor Gene Family: Applications to Animal Disease. [Internet] [Thesis]. Texas A&M University; 2012. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/1969.1/148065.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fisher C1. Diversity and Evolution of the Bovine and Equine Toll-Like Receptor Gene Family: Applications to Animal Disease. [Thesis]. Texas A&M University; 2012. Available from: http://hdl.handle.net/1969.1/148065

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Oregon State University

23. Bellinger, M. Renee. Genomics of migration : from marine distributions of salmonids to mechanisms of olfactory and magnetic cue perception for natal homing.

Degree: PhD, Fisheries Science, 2014, Oregon State University

URL: http://hdl.handle.net/1957/54640

► Substantial scientific investment has been directed towards understanding factors that influence distribution patterns and animals' remarkable ability for precise orientation and navigation, yet fundamental gaps… (more)

▼ Substantial scientific investment has been directed towards understanding factors that influence distribution patterns and animals' remarkable ability for precise orientation and navigation, yet fundamental gaps in our knowledge remain. In my dissertation, I applied emerging genetic technologies to conduct a top-down and bottom-up investigation of animal movement and cue perception. First, in partnership with Project CROOS and the California Salmon Genetic Stock Identification project, stock-specific, marine migratory distributions of Chinook salmon (Oncorhynchus tshawytscha) were characterized for five consecutive months (2010) over 1000 km of coastline. A statistical model was developed to provide measures of relative stockspecific abundance, insights into broad factors that influence migratory distribution, and for fisheries management applications. For the second component of my dissertation, I studied specialized olfactory cells of salmonids that are proposed to contain nanometer-sized magnetite crystals that interact with earth strength magnetic fields to transduce them into neural signals. The transcriptome profiles of candidate magnetoreceptor and non-magnetic cells isolated from olfactory rosette tissue, whole olfactory rosettes, and blood and muscle tissue were characterized from ~661 million Illumina RNA-seq reads. A total of 1,006 differentially expressed genes were identified in the magnetic cell sample type. Results, consistent with having identified genes involved in magnetite crystal formation in fish, were used to develop a genetic model of magnetic sensory perception. Finally, to provide insights into olfaction-based homing that takes place in freshwater, the olfactory repertoire of salmonids was inferred from the Rainbow trout (O. mykiss) genome and compared to that of 15 other teleosts and the jawless fish, sea lamprey (Petromyzon marinus), an ancient species. The abundance and diversity of trace amine-associated and V2R-like genes suggests that these classes of chemoreceptors have biological importance. These findings have relevance for resolving if salmon and other marine organisms imprint on magnetic fields, and contribute to our understanding of how magnetic sense, olfaction, and genetic programming are involved in migratory distributions. Advisors/Committee Members: Banks, Michael A. (advisor), Epps, Clint (committee member).

Subjects/Keywords: Genomics; Salmonidae – Migration

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APA (6^th Edition):

Bellinger, M. R. (2014). Genomics of migration : from marine distributions of salmonids to mechanisms of olfactory and magnetic cue perception for natal homing. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/54640

Chicago Manual of Style (16^th Edition):

Bellinger, M Renee. “Genomics of migration : from marine distributions of salmonids to mechanisms of olfactory and magnetic cue perception for natal homing.” 2014. Doctoral Dissertation, Oregon State University. Accessed February 18, 2020. http://hdl.handle.net/1957/54640.

MLA Handbook (7^th Edition):

Bellinger, M Renee. “Genomics of migration : from marine distributions of salmonids to mechanisms of olfactory and magnetic cue perception for natal homing.” 2014. Web. 18 Feb 2020.

Vancouver:

Bellinger MR. Genomics of migration : from marine distributions of salmonids to mechanisms of olfactory and magnetic cue perception for natal homing. [Internet] [Doctoral dissertation]. Oregon State University; 2014. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/1957/54640.

Council of Science Editors:

Bellinger MR. Genomics of migration : from marine distributions of salmonids to mechanisms of olfactory and magnetic cue perception for natal homing. [Doctoral Dissertation]. Oregon State University; 2014. Available from: http://hdl.handle.net/1957/54640

24. Baur, Brittany. Identifying Regulators from Multiple Types of Biological Data in Cancer.

Degree: 2017, Marquette University

URL: https://epublications.marquette.edu/dissertations_mu/706

► Cancer genomes accumulate alterations that promote cancer cell proliferation and survival. Structural, genetic and epigenetic alterations that have a selective advantage for tumorigenesis affect key… (more)

▼ Cancer genomes accumulate alterations that promote cancer cell proliferation and survival. Structural, genetic and epigenetic alterations that have a selective advantage for tumorigenesis affect key regulatory genes and microRNAs that in turn regulate the expression of many target genes. The goal of this dissertation is to leverage the alteration-rich landscape of cancer genomes to detect key regulatory genes and microRNAs. To this end, we designed a feature selection algorithm to identify DNA methylation signals around a gene that would highly predict its expression. We found that genes whose expression could be predicted by DNA methylation accurately were enriched in Gene Ontology terms related to the regulation of various biological processes. This suggests that genes controlled by DNA methylation are regulatory genes. We also developed two tools that infer relationships between regulatory genes and target genes leveraging structural and epigenetic data. The first tool, ProcessDriver integrates copy number alteration and gene expression datasets to identify copy number cancer driver genes, target genes of these drivers and the disrupted biological processes. Our results showed that driver genes selected by ProcessDriver are enriched in known cancer genes. Using survival analysis, we showed that drivers are linked to new tumor events after initial treatment. The second tool was developed to leverage structural and epigenetic data to infer interactions between regulatory genes and targets on a network-level. Our canonical correlation analysis-based approach utilized the DNA methylation or copy number states of potential regulators and the expression states of potential targets to score regulatory interactions. We then incorporated these regulatory interaction scores as prior knowledge in a dynamic Bayesian framework utilizing time series gene expression data. Our results indicated that the canonical correlation analysis-based scores reflect the true interactions between genes with high accuracy, and the accuracy can be further increased by using the scores as a prior in the dynamic Bayesian framework. Finally, we are developing an algorithm to detect cancer-related microRNAs, associated targets and disrupted biological processes. Our preliminary results suggest that the modules of miRNAs and target genes identified in this approach are enriched in known microRNA-gene interactions. Advisors/Committee Members: Bozdag, Serdar, Merrill, Stephen, Maadooliat, Mehdi.

Subjects/Keywords: Cancer Biology; Genomics

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APA (6^th Edition):

Baur, B. (2017). Identifying Regulators from Multiple Types of Biological Data in Cancer. (Thesis). Marquette University. Retrieved from https://epublications.marquette.edu/dissertations_mu/706

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Baur, Brittany. “Identifying Regulators from Multiple Types of Biological Data in Cancer.” 2017. Thesis, Marquette University. Accessed February 18, 2020. https://epublications.marquette.edu/dissertations_mu/706.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Baur, Brittany. “Identifying Regulators from Multiple Types of Biological Data in Cancer.” 2017. Web. 18 Feb 2020.

Vancouver:

Baur B. Identifying Regulators from Multiple Types of Biological Data in Cancer. [Internet] [Thesis]. Marquette University; 2017. [cited 2020 Feb 18]. Available from: https://epublications.marquette.edu/dissertations_mu/706.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Baur B. Identifying Regulators from Multiple Types of Biological Data in Cancer. [Thesis]. Marquette University; 2017. Available from: https://epublications.marquette.edu/dissertations_mu/706

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

25. Ghosh, Tanay. Study of the transcriptional basis of neuronal function and dysfunction.

Degree: 2008, University of Pune

URL: http://shodhganga.inflibnet.ac.in/handle/10603/2506

►

Expansion of tandem cytosine-adenine-guanine (CAG) trinucleotide repeat encoding an elongated stretch of polyglutamine (polyQ) in the protein has been implicated in a group of neurodegenerative… (more)

Subjects/Keywords: Genomics; Integrative Biology

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APA (6^th Edition):

Ghosh, T. (2008). Study of the transcriptional basis of neuronal function and dysfunction. (Thesis). University of Pune. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/2506

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ghosh, Tanay. “Study of the transcriptional basis of neuronal function and dysfunction.” 2008. Thesis, University of Pune. Accessed February 18, 2020. http://shodhganga.inflibnet.ac.in/handle/10603/2506.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ghosh, Tanay. “Study of the transcriptional basis of neuronal function and dysfunction.” 2008. Web. 18 Feb 2020.

Vancouver:

Ghosh T. Study of the transcriptional basis of neuronal function and dysfunction. [Internet] [Thesis]. University of Pune; 2008. [cited 2020 Feb 18]. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/2506.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ghosh T. Study of the transcriptional basis of neuronal function and dysfunction. [Thesis]. University of Pune; 2008. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/2506

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

26. Chaudhury, Indrajit. Studies on inhibition of gene expression by DNAzymes.

Degree: 2008, University of Pune

URL: http://shodhganga.inflibnet.ac.in/handle/10603/2560

►

DNAzymes are single‐stranded 2‐deoxyoligonucleotides with catalytic activity. 10‐23 DNAzyme being the most efficient RNA‐phosphodiesterase has been extensively utilized in gene silencing. This study demonstrates the… (more)

▼

DNAzymes are single‐stranded 2‐deoxyoligonucleotides with catalytic activity. 10‐23 DNAzyme being the most efficient RNA‐phosphodiesterase has been extensively utilized in gene silencing. This study demonstrates the effectiveness of 10‐23 DNAzyme in silencing several genes of therapeutic interest like inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α) and its receptors TNF‐R1 and TNF‐R2, hepatitis C virus (HCV) RNA. The designed DNAzymes Dz I, II and III cleaved murine iNOS mRNA both in vitro and in vivo. DNAzyme target site I or translation initiation site and site II have computer predicted (MFOLD) secondary structures but site III has no secondary structure. All the three DNAzymes cleaved the short transcripts generated from cloned DNA almost with equal efficiency while cleavage efficiency is higher at site III than the other two sites on isolated iNOS mRNA. Interestingly, at intracellular level, DNAzyme targeted at translation initiation codon (site I) having secondary structure cleaved iNOS mRNA, and suppressed its enzymatic activity and protein expression more efficiently than that targeted at sites II and III. Due to the efficient cleavage activity of the DNAzymes as observed in murine macrophage J774 cells, the DzI and DzIII that target site I and III were further tested in in vivo LPS induced BALB/c mice. Consistent with the previous results in J774 cells, DzI suppressed iNOS expression much more efficiently than DzIII. TNF‐α is a pro‐inflammatory cytokine secreted primarily by activated macrophages. Signaling through the TNF‐α receptors, TNF‐R1 and TNF‐R2 have been implicated in various acute and chronic inflammatory disorders. TNFreceptor mediated activation of NF‐kB is the key step that results in the transcriptional activation of a number of genes which contribute to the succession of inflammatory cascade. We have designed DNAzymes targeting mRNAs of TNF‐α and its receptors.

References p. 81-90 , Appendix p. 91

Advisors/Committee Members: Hari Das, Rakha.

Subjects/Keywords: DNAzymes; Biology; Genomics

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APA (6^th Edition):

Chaudhury, I. (2008). Studies on inhibition of gene expression by DNAzymes. (Thesis). University of Pune. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/2560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chaudhury, Indrajit. “Studies on inhibition of gene expression by DNAzymes.” 2008. Thesis, University of Pune. Accessed February 18, 2020. http://shodhganga.inflibnet.ac.in/handle/10603/2560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chaudhury, Indrajit. “Studies on inhibition of gene expression by DNAzymes.” 2008. Web. 18 Feb 2020.

Vancouver:

Chaudhury I. Studies on inhibition of gene expression by DNAzymes. [Internet] [Thesis]. University of Pune; 2008. [cited 2020 Feb 18]. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/2560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chaudhury I. Studies on inhibition of gene expression by DNAzymes. [Thesis]. University of Pune; 2008. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/2560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign

27. Calla Zalles, Bernarda. Host and pathogen genomics: the molecular repertoire of soybean and Sclerotinia interactions.

Degree: PhD, 0030, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/31918

► Sclerotinia sclerotiorum (Lib.) de Bary is an economically important soybean pathogen in the U.S. and worldwide. Understanding the disease caused by this fungus can help… (more)

Subjects/Keywords: Sclerotinia; soybean; genomics

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APA (6^th Edition):

Calla Zalles, B. (2012). Host and pathogen genomics: the molecular repertoire of soybean and Sclerotinia interactions. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/31918

Chicago Manual of Style (16^th Edition):

Calla Zalles, Bernarda. “Host and pathogen genomics: the molecular repertoire of soybean and Sclerotinia interactions.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed February 18, 2020. http://hdl.handle.net/2142/31918.

MLA Handbook (7^th Edition):

Calla Zalles, Bernarda. “Host and pathogen genomics: the molecular repertoire of soybean and Sclerotinia interactions.” 2012. Web. 18 Feb 2020.

Vancouver:

Calla Zalles B. Host and pathogen genomics: the molecular repertoire of soybean and Sclerotinia interactions. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2020 Feb 18]. Available from: http://hdl.handle.net/2142/31918.

Council of Science Editors:

Calla Zalles B. Host and pathogen genomics: the molecular repertoire of soybean and Sclerotinia interactions. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/31918

University of Notre Dame

28. Dan Liu. Genomic exploration of bacterial habitat adaptation</h1>.

Degree: MS, Biological Sciences, 2013, University of Notre Dame

URL: https://curate.nd.edu/show/th83kw5507d

► In this study we adopted a cross-habitat, comparative genomic approach to identify genetic markers of habitat adaptation in bacterial populations from human gut, marine… (more)

Subjects/Keywords: bacteria; adaptation; genomics

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APA (6^th Edition):

Liu, D. (2013). Genomic exploration of bacterial habitat adaptation</h1>. (Masters Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/th83kw5507d

Chicago Manual of Style (16^th Edition):

Liu, Dan. “Genomic exploration of bacterial habitat adaptation</h1>.” 2013. Masters Thesis, University of Notre Dame. Accessed February 18, 2020. https://curate.nd.edu/show/th83kw5507d.

MLA Handbook (7^th Edition):

Liu, Dan. “Genomic exploration of bacterial habitat adaptation</h1>.” 2013. Web. 18 Feb 2020.

Vancouver:

Liu D. Genomic exploration of bacterial habitat adaptation</h1>. [Internet] [Masters thesis]. University of Notre Dame; 2013. [cited 2020 Feb 18]. Available from: https://curate.nd.edu/show/th83kw5507d.

Council of Science Editors:

Liu D. Genomic exploration of bacterial habitat adaptation</h1>. [Masters Thesis]. University of Notre Dame; 2013. Available from: https://curate.nd.edu/show/th83kw5507d

University of Notre Dame

29. Ryan Edward Butler. The Design and Development of Vectorbase: A Bioinformatic Resource Center for Invertebrate Vectors of Human Pathogens</h1>.

Degree: MS, Biological Sciences, 2010, University of Notre Dame

URL: https://curate.nd.edu/show/gx41mg76x1z

► VectorBase is a Bioinformatics Resource Center for Invertebrate Vectors of Hu- man Pathogens funded by NIAID. It is a centralized relational database based on… (more)

Subjects/Keywords: BRC; Genomics; Annotation

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APA (6^th Edition):

Butler, R. E. (2010). The Design and Development of Vectorbase: A Bioinformatic Resource Center for Invertebrate Vectors of Human Pathogens</h1>. (Masters Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/gx41mg76x1z

Chicago Manual of Style (16^th Edition):

Butler, Ryan Edward. “The Design and Development of Vectorbase: A Bioinformatic Resource Center for Invertebrate Vectors of Human Pathogens</h1>.” 2010. Masters Thesis, University of Notre Dame. Accessed February 18, 2020. https://curate.nd.edu/show/gx41mg76x1z.

MLA Handbook (7^th Edition):

Butler, Ryan Edward. “The Design and Development of Vectorbase: A Bioinformatic Resource Center for Invertebrate Vectors of Human Pathogens</h1>.” 2010. Web. 18 Feb 2020.

Vancouver:

Butler RE. The Design and Development of Vectorbase: A Bioinformatic Resource Center for Invertebrate Vectors of Human Pathogens</h1>. [Internet] [Masters thesis]. University of Notre Dame; 2010. [cited 2020 Feb 18]. Available from: https://curate.nd.edu/show/gx41mg76x1z.

Council of Science Editors:

Butler RE. The Design and Development of Vectorbase: A Bioinformatic Resource Center for Invertebrate Vectors of Human Pathogens</h1>. [Masters Thesis]. University of Notre Dame; 2010. Available from: https://curate.nd.edu/show/gx41mg76x1z

University of Southern California

30. Hu, Tina T. Comparative genomics of arabidopsis thaliana.

Degree: PhD, Computational Biology & Bioinformatics, 2009, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/141933/rec/1495

► The highly selﬁng Arabidopsis thaliana differs from its closest relative, the obligate outcrosser A. lyrata, both in genome size and organization. During approximately 5 million… (more)

Subjects/Keywords: arabidopsis; comparative genomics

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APA (6^th Edition):

Hu, T. T. (2009). Comparative genomics of arabidopsis thaliana. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/141933/rec/1495

Chicago Manual of Style (16^th Edition):

Hu, Tina T. “Comparative genomics of arabidopsis thaliana.” 2009. Doctoral Dissertation, University of Southern California. Accessed February 18, 2020. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/141933/rec/1495.

MLA Handbook (7^th Edition):

Hu, Tina T. “Comparative genomics of arabidopsis thaliana.” 2009. Web. 18 Feb 2020.

Vancouver:

Hu TT. Comparative genomics of arabidopsis thaliana. [Internet] [Doctoral dissertation]. University of Southern California; 2009. [cited 2020 Feb 18]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/141933/rec/1495.

Council of Science Editors:

Hu TT. Comparative genomics of arabidopsis thaliana. [Doctoral Dissertation]. University of Southern California; 2009. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/141933/rec/1495

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