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Schwartz, Marín Ernesto. "Genomic sovereignty and "the Mexican genome"." Thesis, University of Exeter, 2011. http://hdl.handle.net/10036/3500.
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This PhD seeks to explore the development of a bio-molecular (i.e., genomic) map as a sovereign resource in Mexico. The basic analytical thread of the dissertation is related to the circulation of genomic variability through the policy/legal and scientific social worlds that compose the Mexican medical-population genomics arena. It follows the construction of the Mexican Institute of Genomic Medicine (INMEGEN), the notion of genomic sovereignty, and the Mexican Genome Diversity Project (MGDP).The key argument for the construction of the INMEGEN relied in a nationalist policy framing, which considered the Mexican genome as a sovereign resource, coupling Mexican “uniqueness” to the very nature of genomic science. Nevertheless, the notion of genomic sovereignty was nothing similar to a paradigm, and was not based on shared visions of causality, since the very “nature” of the policy object —Mexican Genome— was, and still is, a disputed reality. It was through the rhetoric upon independence, emancipation and biopiracy: i.e. experiences of dispossession “in archaeology, botany or zoology” (IFS 2001: 25) that the novelty of population genomics became amenable to be understood as a sovereign matter. Therefore, the strategic reification of Mexicanhood fuelled the whole policy and the legal agenda of the INMEGEN as well, which permitted cooperation without consensus and opened the process of policy innovation. Conversely, scientists considered genomic sovereignty an unfounded exaggeration, but anyhow they cooperated and even created a new policy and scientific enterprise. Genomic sovereignty exemplifies the process of cooperation without consensus on its most extreme version .So, as the notion circulated and gradually became a law to protect Mexican genomic patrimony, the initial coalition of scientists, lawyers and policy makers disaggregated. Many of the original members of the coalition now think of genomic sovereignty as a strategy of the INMEGEN to monopolise genomic research in the country. This dissertation additionally explores the way in which the MGDP is constructed in mass media, in INMEGEN´s communication and in the laboratory practices. These different dimensions of the MGDP depict the difficulties that emerge between the probabilistic, relative and multiple constructions of population genomics and the rhetorical strategies to continually assert the existence of the unique “Mexican Genome”. I argue that the Mexican case study provides an entry point to what I and others (Benjamin 2009; Schwartz-Marin 2011) have identified as a postcolonial biopolitics in which the nation state is reasserted rather than diluted. However the relation between sovereignty, race and nation is not mediated by the biological purification of the nation (Agamben 1998; Foucault 2007), or the active participation of citizens looking to increase their vitality (Rose 2008, Rose & Rabinow 2006), but on an awareness of subalternity in the genomic arena and a collective desire to compete in the biomedical global economy.
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Pfeifer, Bastian [Verfasser]. "Whole-genome population genomic analyses / Bastian Pfeifer." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2015. http://d-nb.info/1065803222/34.
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Davenport, Colin. "Genomic and metagenomic application of microbial genome signatures." Hannover Bibliothek der Medizinischen Hochschule Hannover, 2010. http://d-nb.info/100117173X/34.
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Ozato, Junior Tadaiti. "Complementação do seqüenciamento do genoma do Southern bean mosaic virus, isolado São Paulo, expressão da porção C-terminal da polimerase e produção de anti-soro policlonal /." São José do Rio Preto : [s.n.], 2007. http://hdl.handle.net/11449/92490.
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Orientador: José Osmar GasparBanca: Claudia Regina Bonini Domingos
Banca: Eliezer Rodrigues de Souto
Resumo: O presente trabalho consistiu no seqüenciamento e caracterização molecular das Cadeias Abertas de Leitura (Open Reading Frames - ORFs) 2 e 3 do genoma do isolado São Paulo do Southern bean mosaic virus (SBMV-SP), completando-se o seqüenciamento de todo o genoma desse isolado. A ORF 2 codifica uma poliproteína (serino protease - VPg - RNA polimerase RNA-dependente) e a ORF 3 um produto com função desconhecida. O seqüenciamento da ORF 2 apresentou 2889 nucleotídeos, incluindo-se o códon de terminação UGA, com 962 aminoácidos deduzidos e massa molecular estimada de aproximadamente 105 kDa. Dentro da ORF 2, localiza-se a ORF 3 contendo 398 nucleotídeos, incluindo-se o códon de terminação UAA, com 132 aminoácidos e massa molecular estimada de aproximadamente 15 KDa. A análise feita a partir das seqüências das ORFS 2 e 3 do genoma do SBMV-SP, quando comparadas com outras espécies do mesmo gênero e isolados do SBMV, depositadas no GenBank, mostrou que a ORF 2 apresenta maior identidade (91,4% na seqüência de nucleotídeos e 95,0% na seqüência de aminoácidos deduzidos) com o isolado de Arkansas. Resultado similar foi obtido em relação à ORF 3 com valores de identidade de 97,0% tanto para as seqüências de nucleotídeos e aminoácidos deduzidos. Dados de filogenia corroboram os dados de identidade. Regiões conservadas do gênero Sobemovirus também foram identificadas, tais como Sítio de Ligação à Capa Protéica (CBPS), a tríade catalítica da serino protease (H-D-S) e a seqüência de heptanucleotídeos (TTTAAAC). A expressão em Escherichia coli da porção C-terminal da RNA Polimerase RNA Dependente (RpRd) produziu uma proteína de fusão de aproximadamente 67 kDa no sistema pMAL c2-x e de 30 kDa no sistema pET 28a. Quando a proteína de fusão foi injetada em coelhos houve a produção de anti-soro específico para a proteína recombinante.
Abstract: The present work consisted of the sequencing and molecular characterization of the Open Reading Frames (ORFs) 2 and 3 from the São Paulo isolate genome of Southern bean mosaic virus (SBMV-SP), completing the sequencing of all the genome of this isolate. The ORF 2 encodes a polyprotein (serine protease - VPg - RNA dependent RNA polimarase) and the ORF 3 one product with unknown function. The sequencing of the ORF 2 reveals 2889 nucleotides, including the stop codon (UGA), with 962 deduced amino acids e and estimated molecular weight of approximately 105 kDa. Nested in the ORF 2 were found the ORF 3 with 398 nucleotides, including the stop codon (UAA), with 132 deduced amino acids and estimated molecular weight of approximately 15 kDa. The analysis made from the sequences of the ORFs 2 and 3 from the SBMV-SP genome, when compared with other species of the same gender and isolates of SBMV, deposited in the GenBank, showed that the ORF 2 presents higher identity (91,4% in the nucleotide sequence and 95,0% in the deduced amino acids sequence) with Arkansas isolate. Similar result was obtained in relation to the ORF 3 with identity values of 97,0% for the nucleotides and deduced amino acids sequences. Phylogeny data corroborate the identity data. Conserved regions of the Sobemovirus gender had also been identified such as Coat Protein Binding Site (CPBS), serine protease catalytic triad (H-D-S) and heptanucleotide sequence (TTTAAAC). The Expression in Escherichia coli of the C-terminal region of the RNA dependent RNA polimerase produced a fusion protein of approximately 67 kDa in pMAL c2-x system and a 30 kDa protein in pET 28a system. When the fusion protein ...(Complete abstract click electronic access below)
Mestre
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Groet, Jurgen. "Physical mapping and identification of novel genes in human chromosome 21q11." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312003.
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Merkel, Angelika. "Microsatellite Evolution in The Yeast Genome - A Genomic Approach." Thesis, University of Canterbury. School of Biological Sciences, 2008. http://hdl.handle.net/10092/3327.
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Microsatellites are short (1-6bp long) highly polymorphic tandem repeats, found in all genomes analyzed so far. Popular genetic markers for many applications including population genetics, pedigree analysis, genetic mapping and linkage analysis, some microsatellites also can cause a variety of human neurodegenerative diseases and may act as agents of adaptive evolution through the regulation of gene expression. As a consequence of these diverse uses and functions, the mutational and evolutionary dynamics of microsatellite sequences have gained much attention in recent years. Mostly, the focus of studies investigating microsatellite evolution has been to develop more refined evolutionary models for estimating parameters such as genetic distance or linkage disequilibrium. However, there is an incentive in using our understanding of the evolutionary processes that affect these sequences to examine the functional implications of microsatellite evolution. What has emerged from nearly two decades of study are highly complex mutational dynamics, with mutation rates varying across species, loci and alleles, and a multitude of potential influences on these rates, most of which are not yet fully understood. The increasing availability of whole genome sequences has immensely extended the scope for studying microsatellite evolution. For example, where once it was common to examine single loci, it is now possible to examine microsatellites using genome wide approaches. In the first part of my dissertation I discuss approaches and issues associated with detecting microsatellites in genomic data. In Chapter 2 I undertook a meta-analysis of studies investigating the distribution of microsatellites in yeast and showed that studies comparing the distribution of microsatellites in genomic data can be fraught due to the application of different definitions for microsatellites by different investigators. In particular, I found that variation in how investigators choose the repeat unit size of a microsatellite, handle imperfections in the array and especially the choice of minimum array length used, leads to a large divergence in results and can distort the conclusions drawn from such studies, particularly where inter-specific comparisons are being made. In a review of the currently available suite of bioinformatics tools (Chapter 3), I further showed that this bias extends beyond a solely theoretical controversy into a methodological issue because most software tools not only incorporate different definitions for the key parameters used to define microsatellites, but also employ different strategies to search and filter for microsatellites in genomic data. In this chapter I provide an overview of the available tools and a practical guide to help other researchers choose the appropriate tool for their research purpose. In the second part of my thesis, I use the analytical framework developed from the previous chapters to explore the biological significance of microsatellites exploiting the well annotated genome of the model organism Saccharomyces cerevisiae (baker’s yeast). Several studies in different organisms have indicated spatial associations between microsatellites and individual genomic features, such as transposable elements, recombinational hotspots, GC-content or local substitution rate. In Chapter 4, I summarized these studies and tested some of the underlying hypotheses on microsatellite distribution in the yeast genome using Generalized Linear Models (GLM) and wavelet transformation. I found that microsatellite type and distribution within the genome is strongly governed by local sequence composition and negative selection in coding regions, and that microsatellite frequency is inversely correlated with SNP density reflecting the stabilizing effect point mutations have on microsatellites. Microsatellites may also be markers for recent genome modifications, due to their depletion in regions nearby LTR transposons, and elements of potential structural importance, since I found associations with features such as meiotic double strand breaks, regulatory sites and nucleosomes. Microsatellites are subject to local genomic influences, particularly on small (1-2kb) scales. Although, these local scale influences might not be as dominant as other factors on a genome-wide scale they are certainly of importance with respect to individual loci. Analysis of locus conservation across 40 related yeast strains (Chapter 5) showed no bias in the type of microsatellites conserved, only a negative influence of coding sequences, which supports again the idea that microsatellites evolve neutrally. Polymorphism was rare, and despite a positive correlation with array length, there was no relationship with either genomic fraction or repeat size. However, the analysis also revealed a non-random distribution of microsatellites in genes of functionally distinct groups. For example, conserved microsatellites (similar to general microsatellites in yeast) are mostly found in genes associated with the regulation of biological and cellular processes. Polymorphic loci show further an association with the organization and biogenesis of cellular components, morphogenesis, development of anatomical structures and pheromone response, which, is absent for monomorphic loci. Whether this distribution is an indication of functionality or simply neutral mutation (e.g. genetic hitch-hiking) is debatable since most conserved microsatellites, particularly variable loci, are located within genes that show low selective constraints. Overall, microsatellites appear as neutrally evolving sequences, but owing to the sheer number of loci within a single genome, individual loci may well acquire some functionality. More work is definitely needed in this area, particularly experimental studies, such as reporter-gene expression assays, to confirm phenotypic effects.
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Bradwell, Katie. "Genomic comparisons and genome architecture of divergent Trypanosoma species." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4598.
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Virulent Trypanosoma cruzi, and the non-pathogenic Trypanosoma conorhini and Trypanosoma rangeli are protozoan parasites with divergent lifestyles. T. cruzi and T. rangeli are endemic to Latin America, whereas T. conorhini is tropicopolitan. Reduviid bug vectors spread these parasites to mammalian hosts, within which T. rangeli and T. conorhini replicate extracellularly, while T. cruzi has intracellular stages. Firstly, this work compares the genomes of these parasites to understand their differing phenotypes. Secondly, genome architecture of T. cruzi is examined to address the effect of a complex hybridization history, polycistronic transcription, and genome plasticity on this organism, and study its highly repetitive nature and cryptic genome organization. Whole genome sequencing, assembly and comparison, as well as chromosome-scale genome mapping were employed. This study presents the first comprehensive whole-genome maps of Trypanosoma, and the first T. conorhini strain ever sequenced. Original contributions vii to knowledge include the ~21-25 Mbp assembled genomes of the less virulent T. cruzi G, T. rangeli AM80, and T. conorhini 025E, containing ~10,000 to 13,000 genes, and the ~36 Mbp genome assembly of highly virulent T. cruzi CL with ~24,000 genes. The T. cruzi strains exhibited ~74% identity to proteins of T. rangeli or T. conorhini. T. rangeli and T. conorhini displayed greater complex carbohydrate metabolic capabilities, and contained fewer retrotransposons and multigene family copies, e.g. mucins, DGF-1, and MASP, compared to T. cruzi. Although all four genomes appear highly syntenic, T. rangeli and T. conorhini exhibited greater karyotype conservation. T. cruzi genome architecture studies revealed 66 maps varying from 0.13 to 2.4 Mbp. At least 2.6% of the genome comprises highly repetitive repeat regions, and 7.4% exhibits repetitive regions barren of labels. The 66 putative chromosomes identified are likely diploid. However, 20 of these maps contained regions of up to 1.25 Mbp of homology to at least one other map, suggestive of widespread segmental duplication or an ancient hybridization event that resulted in a genome with significant redundancy. Assembled genomes of these parasites closely reflect their phylogenetic relationships and give a greater context for understanding their divergent lifestyles. Genome mapping provides insight on the genomic evolution of these parasites.
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Rumrill, Deborah. "Initiating international collaboration : a study of the human genome organization /." Thesis, This resource online, 1993. http://scholar.lib.vt.edu/theses/available/etd-09122009-040530/.
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Boardman, Anelda Philine. "Assessment of genome visualization tools relevant to HIV genome research: development of a genome browser prototype." Thesis, University of the Western Cape, 2004. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_3632_1185446929.
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Over the past two decades of HIV research, effective vaccine candidates have been elusive. Traditionally viral research has been characterized by a gene -by-gene approach, but in the light of the availability of complete genome sequences and the tractable size of the HIV genome, a genomic approach may improve insight into the biology and epidemiology of this virus. A genomic approach to finding HIV vaccine candidates can be facilitated by the use of genome sequence visualization. Genome browsers have been used extensively by various groups to shed light on the biology and evolution of several organisms including human, mouse, rat, Drosophila and C.elegans. Application of a genome browser to HIV genomes and related annotations can yield insight into forces that drive evolution, identify highly conserved regions as well as regions that yields a strong immune response in patients, and track mutations that appear over the course of infection. Access to graphical representations of such information is bound to support the search for effective HIV vaccine candidates. This study aimed to answer the question of whether a tool or application exists that can be modified to be used as a platform for development of an HIV visualization application and to assess the viability of such an implementation. Existing applications can only be assessed for their suitability as a basis for development of an HIV genome browser once a well-defined set of assessment criteria has been compiled.
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Shaw, Daniel 1993. "Streamlining minimal bacterial genomes : Analysis of the pan bacterial essential genome, and a novel strategy for random genome deletions in Mycoplasma pneumoniae." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/668244.
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Understanding what constitutes a true Minimal Cell is a key challenge in synthetic biology. In this work, we present two new tools to aid in this endeavour. i) A novel methodology for minimising the Mycoplasma pneumoniae genome via random deletions of genetic material. This protocol utilises the Cre Lox system coupled with random transposon mutagenesis to create a population with random lox sites dispersed around the genome. This allows for a population of cells containing a high variability of large and small-scale deletions ranging from 50bp to 25Kb within M. pneumoniae. ii) The first large scale analysis of the essentiality of genes from multiple bacterial species, and how the composition and function of the essential genome of a bacterium changes based on the genome’s complexity.Discernir cuales son los componentes que podrían constituir una célula mínima es un desafío clave para la Biología Sintética. En esta tesis, se presentan dos nuevas herramientas para facilitar esta tarea. (i) Una nueva metodología para minimizar el genoma de Mycoplasma pneumoniae mediante la deleción aleatoria de material genético. Esta técnica combina el sistema Cre/lox con la mutagénesis aleatoria mediada por transposones para generar poblaciones bacterianas en las que los sitios lox están distribuidos de manera aleatoria a lo largo de su genoma. Esto permite la generación de poblaciones bacterianas en las que el tamaño de las deleciones efectuadas varia desde 50 pb hasta 25 kb. (ii) El primer análisis a gran escala de la esencialidad genética en múltiples especies bacterianas, y cómo la composición y función del grupo de genes esenciales de una bacteria cambia en función de la complejidad de su genoma.
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Wong, Chi-fat, and 黃志發. "Genome sequencing and comparative genomic analysis of Pseudomonas mendocina DLHK." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/197162.
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Nitrogen oxides are targeted as important gas pollutants to be eliminated. Biological removal of nitrogen oxides, like the use of bio-trickling reactor, is gaining popularity over conventional methods. A bacterium isolated from a bio-trickling reactor showing high performance in removing nitrogen oxides was identified to be Pseudomonas mendocina. The genome of this isolate was sequenced using 454 pyrosequencing technology to a high level of completeness with 33 contigs and N50 contig length of 273 kbp. The genome was annotated by Prokaryotic Genome Automatic Annotaion Pipeline (PGAAP)and the strain was named P. mendocina DLHK. Examination of P. mendocina DLHK genome annotation found nitrate reductase but not nitrite reductase, nitric oxide reductase and nitrous oxide reductase. Novel genes or pathways might be available in P. mendocina DLHK contributingits denitrification function in the bio-trickling reactor.
To better understand the evolution of Pseudomonas, a comprehensive comparative study was performed. Genomes of the Pseudomonasgenus were reannotated. Core genes were extracted to construct a phylogenomic tree using supermatrix approach. Effectiveness of using single phylogenetic marker in constructing phylogeny of Pseudomonas was evaluated using rpoB gene marker. Both methods generated phylogenetic trees of very similar topology, suggesting that rpoB gene can be a very effective marker in the rapid construction of Pseudomonas phylogeny.It is surprising to note that Azotobacter vinelandii DJ was included in the large clade of Pseudomonas and have the closest relationship with P. stutzeri in both phylogenetic trees, providing evidence that this species should be reclassified into the genus Pseudomonas.
Cluster of Orthologous Groups (COG)category distribution of all pseudomonads were analysed for physiological significance. The large amount of gene categorised into the COG for amino acid metabolism and transcription may imply the importance for these 2 functions on the survival of pseudomonads. It is again surprising to note the COG distribution pattern of A. vinelandii DJ is different from other pseudomonads, especially to its closest phylogenetic neighbour P. stutzeri.
Horizontal gene transfer events inpseudomonads were investigated because of its importance in prokaryotic evolution. The high congruence of the phylogemonic tree to most core genes suggests that the phylogenomic tree is a good piece of evidence describing the evolution of pseudomonads. It is a bit surprising to observe that quite a number of core genes may have exhibited horizontal gene transfer which show incongruence of the gene tree to the core genes. The impact of horizontal gene transfer events on the functionality and evolution of pseudomonads remains to be investigated.published_or_final_version
Biological Sciences
Master
Master of Philosophy
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Chan, Yujia Alina. "DNA:RNA hybrid genome-wide profiling and links to genomic instability." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/46327.
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De, Subhajyoti. "Human genome evolution : investigating protein divergence, polymorphisms and genomic neighbourhood." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612500.
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Feijão, Pedro Cipriano 1975. "On genome rearrangement models = Sobre modelos de rearranjo de genomas." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/275689.
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Orientador: João MeidanisTese (doutorado) - Universidade Estadual de Campinas, Instituto de Computação
Made available in DSpace on 2018-08-21T17:01:05Z (GMT). No. of bitstreams: 1 Feijao_PedroCipriano_D.pdf: 1943126 bytes, checksum: 4c547e8c568bbd0f2eb8235dfde05524 (MD5) Previous issue date: 2012
Resumo: Rearranjo de genomas é o nome dado a eventos onde grandes blocos de DNA trocam de posição durante o processo evolutivo. Com a crescente disponibilidade de sequências completas de DNA, a análise desse tipo de eventos pode ser uma importante ferramenta para o entendimento da genômica evolutiva. Vários modelos matemáticos de rearranjo de genomas foram propostos ao longo dos últimos vinte anos. Nesta tese, desenvolvemos dois novos modelos. O primeiro foi proposto como uma definição alternativa ao conceito de distância de breakpoint. Essa distância é uma das mais simples medidas de rearranjo, mas ainda não há um consenso quanto à sua definição para o caso de genomas multi-cromossomais. Pevzner e Tesler deram uma definição em 2003 e Tannier et al. a definiram de forma diferente em 2008. Nesta tese, nós desenvolvemos uma outra alternativa, chamada de single-cut-or-join (SCJ). Nós mostramos que, no modelo SCJ, além da distância, vários problemas clássicos de rearranjo, como a mediana de rearranjo, genome halving e pequena parcimônia são fáceis, e apresentamos algoritmos polinomiais para eles. O segundo modelo que apresentamos é o formalismo algébrico por adjacências, uma extensão do formalismo algébrico proposto por Meidanis e Dias, que permite a modelagem de cromossomos lineares. Esta era a principal limitação do formalismo original, que só tratava de cromossomos circulares. Apresentamos algoritmos polinomiais para o cálculo da distância algébrica e também para encontrar cenários de rearranjo entre dois genomas. Também mostramos como calcular a distância algébrica através do grafo de adjacências, para facilitar a comparação com outras distâncias de rearranjo. Por fim, mostramos como modelar todas as operações clássicas de rearranjo de genomas utilizando o formalismo algébrico
Abstract: Genome rearrangements are events where large blocks of DNA exchange places during evolution. With the growing availability of whole genome data, the analysis of these events can be a very important and promising tool for understanding evolutionary genomics. Several mathematical models of genome rearrangement have been proposed in the last 20 years. In this thesis, we propose two new rearrangement models. The first was introduced as an alternative definition of the breakpoint distance. The breakpoint distance is one of the most straightforward genome comparison measures, but when it comes to defining it precisely for multichromosomal genomes, there is more than one way to go about it. Pevzner and Tesler gave a definition in a 2003 paper, and Tannier et al. defined it differently in 2008. In this thesis we provide yet another alternative, calling it single-cut-or-join (SCJ). We show that several genome rearrangement problems, such as genome median, genome halving and small parsimony, become easy for SCJ, and provide polynomial time algorithms for them. The second model we introduce is the Adjacency Algebraic Theory, an extension of the Algebraic Formalism proposed by Meidanis and Dias that allows the modeling of linear chromosomes, the main limitation of the original formalism, which could deal with circular chromosomes only. We believe that the algebraic formalism is an interesting alternative for solving rearrangement problems, with a different perspective that could complement the more commonly used combinatorial graph-theoretic approach. We present polynomial time algorithms to compute the algebraic distance and find rearrangement scenarios between two genomes. We show how to compute the rearrangement distance from the adjacency graph, for an easier comparison with other rearrangement distances. Finally, we show how all classic rearrangement operations can be modeled using the algebraic theory
Doutorado
Ciência da Computação
Doutor em Ciência da Computação
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Jordan, Barbara M. (Barbara Marie) 1975. "Genome complexity reduction for genome-wide single nucleotide polymorphism analysis." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/8319.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2002.Vita.
Includes bibliographical references.
Millions of single nucleotide polymorphisms (SNPs) have been identified in the human genome, and more are cataloged every day. The challenge now is to use these SNPs to discover the genetic risk factors underlying common and complex diseases. Efficient, large-scale genotyping methods are one necessary component of this endeavor. Current SNP genotyping techniques all rely on an initial PCR amplification of each SNP locus. Individual or low-level multiplexed PCR reactions are sufficient for genotyping a few to a few hundred different SNPs, but genome-wide linkage and association studies in humans will require thousands to tens of thousands of different SNPs, each typed on a few thousand individuals. To efficiently reach this goal, PCR techniques capable of amplifying a few hundred loci per reaction are needed. To meet this need we investigated the use of PCR-based genome complexity reduction methods for SNP genotyping. We discovered that degenerate oligonucleotide primed PCR (DOP-PCR) is capable of amplifying a specific fraction of a genome in a highly reproducible manner. The genomic sequences amplified are determined by the oligonucleotide primer's nondegenerate, 8-12 nucleotide, 3' end sequence. The amplified complexity can be varied from one to over 10,000 loci by changing the DOP-PCR primer's length and specific sequence. We collected SNPs from a human DOP-PCR that amplifies roughly 600 loci, and demonstrated that about half of the SNPs tested could be genotyped directly from the DOP-PCR product mixture, using the allele specific oligonucleotide hybridization genotyping technique.
(cont.) We investigated using the human genome sequence to electronically predict, based on DOP-PCR primer 3' end sequence, the products of DOP-PCRs. We successfully demonstrated that approximately 80% of such predicted products were in fact amplified in DOP-PCRs done with human genomic DNA. Electronic prediction of DOP-PCR products, and the SNPs contained in them from SNP databases, could provide a method to compile a set of DOP-PCRs that amplify tens of thousands of SNP loci for genome-wide scans. We also tested SNP genotyping from a mouse DOP-PCR amplifying about 200 loci, and from several Arabidopsis thaliana DOP-PCRs that amplify about 100 loci each. Half of the SNPs collected in these DOP-PCRs were also amenable to genotyping, directly from the DOP-PCR product mixtures. We identified SNPs in these DOP-PCRs by resequencing, but as more species' genomes are sequenced and more SNPs are contributed to public databases, DOP-PCR will become easier to implement in these and other model organisms. Currently, we are developing a genome-wide set of SNPs amplified in 32 DOP-PCRs for the mouse.
by Barbara M. Jordan.
Ph.D.
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Goupil, Alix. "Genome instability : from genome content variations to gene expression plasticity." Electronic Thesis or Diss., Université Paris sciences et lettres, 2021. http://www.theses.fr/2021UPSLS053.
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La plupart de nos cellules sont diploïdes possédant deux copies de chaque chromosome. Lors de la mitose, la formation d’un fuseau bipolaire avec un centrosome à chaque pôle permet la ségrégation correcte des chromosomes, essentiel au maintien de la stabilité génétique. Il existe néanmoins des variations du contenu chromosomique comme la polyploïdie, définit comme le doublement de l’ensemble des chromosomes et l’aneuploïdie, définie comme la perte ou le gain de chromosome entier. Bien qu’observées, la fréquence des cellules aneuploïdies dans les tissus d’un organisme sain reste controversée.De façon importante, la duplication du génome et l’aneuploïdie sont associées à des pathologies et sont considérées comme une caractéristique du cancer. En effet, un nombre anormal de chromosomes est souvent associé à une instabilité chromosomique. Toutefois le rôle et les implications de ces variations dans l’initiation et la progression de tumeur restent peu compris.J’ai d’abord étudié les conséquences de la polyploïdie sur la division des cellules. J’ai utilisé des approches in vivo et in vitro en induisant la polyploidisation par défaut de cytocinèse dans des cellules souches neurales de drosophile et des cellules cancéreuses humaines. L’analyse de leur mitose m’a permis de découvrir que la présence de chromosomes et de centrosomes en excès conduisait invariablement à la formation de fuseaux multipolaires. En modélisant les cellules polyploïdes, j’ai découvert qu’au-delà de la quantité, la conformation spatiale de l’ADN contribue à cette multipolarité. Des perturbations expérimentales au niveau de l’ADN et du fuseau m’ont permis de démontrer que la présence d’ADN en excès agit comme une barrière physique bloquant la coalescence des multiples pôles et par conséquent empêchant la bipolarité. De façon intéressante, j’ai réussi à restaurer la bipolarité en supprimant la « barrière d’ADN » par ablation avec laser ou en augmentant la longueur des microtubules pour contourner celle-ci. Alors que l’amplification centrosomale était considérée comme unique acteur, mes résultats identifient l’excès d’ADN comme contributeur clef de la multipolarité et de l’instabilité chromosomique typique des cellules polyploïdes.Puis, je me suis ensuite intéressée à l’aneuploïdie, dont la fréquence en contexte sain reste un sujet de débat intense. De plus, les outils développés jusqu’à présent pour évaluer le taux d’aneuploïdie manque d’une dimension temporelle. J’ai donc généré un outil génétique innovant de visualisation et de suivi des cellules aneuploïdes in vivo chez la drosophile. J’ai utilisé l’expression de la GFP comme gène rapporteur, contrôlée par le système GAL4/UAS et son inhibition par GAL80. Ainsi, la perte aléatoire du chromosome contenant la séquence du GAL80 entraine l’apparition d’un signal GFP dans les cellules aneuploïdes. Celles-ci peuvent donc être facilement détectées et suivies en temps-réel dans les tissus. Utilisant ce système, j’ai découvert que la perte de chromosome était un évènement très rare dans les tissus de la mouche. Cet outil combiné à d’autres marqueurs fluorescents et/ou utilisé dans divers contextes génétiques pourrait aider à la compréhension de la genèse et du devenir des cellules aneuploïdes in vivo.De plus, j’ai constaté que le cerveau de la larve présentait un nombre important de cellules GFP. De manière surprenante, ces cellules ne résultaient pas de la perte de chromosomes mais de la perte d’expression du gène GAL80. Ces résultats inattendus ont de fortes implications pour la communauté des drosophilistes car cela peut mener à des faux positifs dans les expériences de génération de clones. J’ai aussi découvert que les cellules souches neurales présentaient un mosaïsme dans l’expression des gènes, qui diffèrent d’autres organes et s’adaptent à des stimuli environnementaux. Ceci représente possiblement un niveau de plasticité dans le cerveau nécessaire à la diversité neuronale, l’adaptation et la survieMost animal cells are diploid, containing two copies of each chromosome. Establishment of proper bipolar mitotic spindle containing two centrosomes, one at each pole contributes to accurate chromosome segregation. This is essential for the maintenance of genome stability, tissue and organism homeostasis. However, numerical deviations to the diploid set are observed in healthy tissues. Polyploidy is the doubling of the whole chromosome set and aneuploidy concerns the gain or loss of whole chromosomes. Importantly, whole genome duplications and aneuploidy have also been associated to pathological conditions. For example, variations to genome content are associated with chromosome instability and cancer development, however their exact contribution to cancer genome remains poorly understood.In the first part of my PhD project, I investigated the consequences of polyploidy during cell division. I found that the presence of extra DNA and extra centrosomes generated invariably multipolar spindles. Then I identified contributors to the multipolar status using in vivo approaches in Drosophila neural stem cells and in vitro culture of cancer cells. Further I combined DNA and spindle perturbations with computer modelling and found that in polyploid cells, the presence of excessive DNA acts as a physical barrier blocking spindle pole coalescence and bipolarity. Indeed, laser ablation to disrupt and increase in microtubule stability and length to bypass the DNA-barrier could rescue bipolar spindle formation. This discovery challenges the current view that suggested extra-centrosomes as only contributor to spindle multipolarity and provides a rational to understand chromosome instability typical of polyploid cells.The aim of the second part of my PhD project was to generate a novel tool to quantitively probe chromosome loss in vivo in Drosophila tissues. Aneuploidy has been observed in various physiological tissues, however the frequency of this error remained highly debatable. In addition, tools developed so far to assess aneuploidy lack a temporal dimension. To circumvent this, I used the expression of a GFP report gene driven by the GAL4/UAS system and its inhibition by GAL80. In principle, the random loss of the chromosome carrying the GAL80 sequence leads to GFP appearance in aneuploid cells that can therefore be followed in live tissues. I found that chromosome loss was extremely infrequent in most tissues of the wild type fly. This tool combined with fluorescent marker and/or tested in various genetic background, might help understanding mechanisms behind aneuploidy genesis and outcome in vivo.While developing this tool, I discovered that in the larval brain, GFP cells where not a by-product of chromosome loss but rather an unexpected mis-regulation in the expression of the GAL80 gene. These results have strong implications for the Drosophila community as it can result in false positive in clonal experiments. Further, I discovered a mosaicism and plasticity of the Drosophila brain in neural stem cells for gene expression which differs from other organs and that is influenced by environmental stimuli. This possibly reflects a certain level of plasticity in the brain necessary for neuronal diversity, adaptation and survival
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Greig, Duncan. "Sex, species and Saccharomyces cerevisiae." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301401.
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Julca, Chávez Irene Consuelo. "Analysis of the Olive genome." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/459083.
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El olivo (Olea europaea, Oleaceae) es una planta icónica en el Mediterráneo por razones culturales, históricas y biológicas. El olivo como especie está formado por seis subespecies (europaea, maroccana, cerasiformis, laperrinei, guanchica, y cuspidata) que juntas forman el llamado complejo O. europaea. Del mismo modo, la subsp. europaea se divide en dos variedades: var. europaea, que comprende las formas cultivadas, y var. sylvestris (también llamado oleaster), que incluye las formas silvestres del Mediterráneo. El olivo ha sido cultivado intensivamente desde hace aproximadamente 6,000 años, coincidiendo con la emergencia de civilizaciones tempranas en el Mediterráneo. Debido al gran interés en sus frutos, como aceitunas de mesa y como material para aceite de oliva, el olivo es considerado un cultivo esencial en la cuenca Mediterránea. Esta tesis doctoral tiene como objetivo aportar conocimientos sobre la biologııa y la evolución de los olivos cultivados y linajes cercanos. Con este fin, secuenciamos, ensamblamos y anotamos un genoma de referencia correspondiente a un único individuo (O. europaea L. var. europaea). Análisis filogenómicos y evaluaciones del coverage relativo de alelos sugieren que en la historia evolutiva del olivo ocurrieron un mıınimo de cuatro poliploidizaciones. Dos alopoliploidizaciones localizadas en la base de la familia Oleaceae (Eoceno - Cretácico tardııo) y en la base de la tribu Oleeae; seguidas de dos poliploidizaciones en el ancestro de O. europaea (Mioceno-Plioceno) luego de su divergencia de Phillyrea angustifolia. Con el objetivo de estudiar la diversidad y las relaciones filogenéticas en el complejo O. europaea, secuenciamos adicionalmente el genoma de al menos un individuo por cada subespecie. Nuestros resultados muestran que los olivos cultivados tienen menos diversidad nucleotııdica cuando son comparados con los linajes silvestres. Diferentes genes están bajo selección positiva en cada cultivariedad incluida en este estudio (‘Arbequina’, ‘Beladi’, ‘Farga’, ‘Picual’, ‘Sorani’). Además de hibridación que involucra poliploidización, los análisis filogenómicos revelaron extensivos procesos de hibridazación homoploide entre los lineajes del complejo O. europaea, que resulta en un continuo flujo genético desde olivos silvestres hacia olivos domesticados. En particular, el cv. ‘Farga’ tiene un origen diferente a las otras cultivariedades incluidas en este estudio y aporta evidencia de domesticación secundaria en la penıınsula Ibérica. En resumen, este estudio permite entender la historia evolutiva de O. europaea, y descubre un complejo escenario de poliploidizaciones e hibridaciones que han resultado en duplicaciones génicas recurrentes.The olive tree (Olea europaea, Oleaceae) is an iconic plant of Mediterranean countries for cultural, historical and biological reasons. The olive species comprises six subspecies (europaea, maroccana, cerasiformis, laperrinei, guanchica, and cuspidata) that together form the so-called O. europaea complex. Likewise, the subsp. europaea is divided into two taxonomic varieties: var. europaea, that comprises all the cultivated forms, and var. sylvestris (also called oleaster), that includes the wild forms. The olive tree has been intensively cultivated since 6,000 years ago, coinciding with the emergence of early Mediterranean civilizations. Because of the interest of the drupes both as table olives and as raw material to produce olive oil, the olive tree is an essential crop across the Mediterranean basin. This doctoral thesis aims to provide insights into the biology and the evolution of the cultivated olive and relatives. To this end, we sequenced, assembled, and annotated a reference genome obtained from a single individual (O. europaea L. var. europaea). Phylogenomic analysis and assessment of allelic relative coverage suggest up to four polyploidization events in the evolutionary history of the olive. Two ancient allopolyploidization events at the base of the family Oleaceae (Eocene-Late Cretaceous), and the tribe Oleeae (Oligocene-Miocene), followed by two polyploidizations in the ancestor of O. europaea (Miocene-Pliocene) since its divergence from Phillyrea angustifolia. In order to study the diversity and phylogenetic relationships in the O. europaea complex, we additionally sequenced the genome of at least one individual per subspecies. Our results show that cultivated olive trees exhibit less nucleotide diversity when compared with wild relatives. Different sets of genes were found to be under positive selection in each cultivar included in this study (‘Arbequina’, ‘Beladi’, ‘Farga’, ‘Picual’, ‘Sorani’). In addition to hybridization involving polyploidization (allopolyploidization), phylogenomic analysis revealed extensive homoploid hybridization among lineages of the O. europaea complex, which results in a continuous gene flow from wild to domesticated olive trees. In particular, cv. ‘Farga’ has a different origin than the other cultivars included in this study, and shows evidence for secondary domestication events in the Iberian Peninsula. In summary, this study helps unravel the evolutionary history of O. europaea, and uncover a complex scenario of polyploidization and hybridization that resulted in recurrent gene duplications.
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Ustun, Cevat. "Improving genome assembly." College Park, Md. : University of Maryland, 2005. http://hdl.handle.net/1903/2957.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2005.Thesis research directed by: Physics. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Christie, David Alan. "Genome rearrangement problems." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284780.
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Griffin, Craig David. "Genome recombination studies." Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/30354.
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In the Saccharomyces cerevisiae genome the regions adjacent to the 32 chromosome ends, the subtelomeres, are tethered at the nuclear periphery during vegetative / somatic growth and during sporulation / gametogenesis. This is in contrast to the rest of the genome, the interstitial regions, which are located throughout the nucleus. There is evidence that recombination between different subtelomeres is the exceptionally frequent, but that subtelomeres and interstitial regions do not recombine. These features of recombination involving subtelomeres may result from a structure that interacts with the subtelomeres, partitioning them from interstitial regions. Our aim was to characterise which part of the subtelomeres this recombination barrier interacts with. As a tool for estimating the rate and efficiency of recombination between different regions, a set of insertions into the S. cerevisiae genome was engineered. This set included 11 insertions at regular intervals along the terminal 10% of one chromosome arm, marking an interstitial region and the subtelomere. In addition, insertions were also made into a sample of other subtelomeres and interstitial regions. Both recombination during vegetative growth (mitotic recombination) and during sporulation (meiotic recombination) were assayed, between numerous combinations of these insertions. In agreement with previous studies, our results indicate that recombination between interstitial regions and subtelomeres is less efficient than recombination between different interstitial regions. Moreover, this is true of both mitotic and meiotic recombination. However, our efficiency data indicate this may result from tethering of subtelomeres at the nuclear periphery, rather than a partition in the nucleus. Tethering may suppress recombination between subtelomeres and most interstitial regions, simply by maintaining a large relative distance between these two regions. In contrast, the efficiency of mitotic and meiotic recombination between subtelomeres appear to be very different. Mitotic recombination between different subtelomeres appears to be exceptionally efficient, while meiotic recombination between different subtelomeres appears to be inefficient.
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Simonaitis, Pijus. "Weighted Genome Rearrangements." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTS041.
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Un réarrangement génomique est une mutation qui modifie la structure des chromosomes voir même leur nombre dans un génome. Outre des fusions et des fissions de chromosomes, ces réarrangements comprennent des délétions, des insertions et des inversions de segments chromosomiques. Deux extrémités de chromosomes différents peuvent également être échangées au cours d'une translocation. L'ensemble de ces mutations constitue un scénario évolutif de réarrangements entre les espèces. Nous nous sommes intéressés à la reconstruction des scénarios de réarrangements entre espèces animales.Notre projet associe des outils mathématiques et algorithmiques avec la compréhension biologique actuelle des réarrangements génomiques. D'un point de vue biologique, notre objectif est de lier génétique et épigénétique aux réarrangements dans les deux sens:1) nous développons une méthodologie pour étudier des caractéristiques génétiques et épigénétiques associées aux réarrangements,2) et inversement pour trouver des scénarios de réarrangements guidés par de telles caractéristiques génétiques et épigénétiques.La principale contribution de cette thèse est la suivante. Nous présentons un cadre sur le modèle de réarrangements double cut and join avec des poids arbitraires. Dans ce cadre un scénario de poids minimum peut être trouvé en temps polynomial parmi les scénarios de longueur minimale pour deux génomes à contenu génétique identique et sans doublons.En plus de cela, nous établissons un certain nombre de nouvelles correspondances entre les divers problèmes de tri. Ces problèmes incluent le tri des génomes avec des réarrangements dits Double Cut and Join, le tri des graphes avec 2-breaks ou edge swaps, le tri des permutations avec des transpositions, le tri des chaînes avec des échanges et l'échange de jetons sur les graphesRecent advances in sequencing technologies revealed the ubiquity of genome rearrangements between each and every one of us. These large scale mutationsrearrange segments of chromosomes and have a profound impact on genetic variation, disease, and evolution. The study of the consequences of rearrangements along with their molecular mechanisms, however, is still in its infancy.Given extant genomes, we are interested in tracing back the evolutionary rearrangement scenarios that transformed their least common ancestor into the genomes that we observe today. This helps not only to reveal evolutionary relationships between organisms, but also provides a window for the study of genome rearrangements themselves.The central computational problem in this subfield of comparative genomicsis that of finding optimal rearrangement scenarios transforming one genome into another. Historically all rearrangements were treated as being equally possible, and optimal scenarios were those that contained the minimum number of rearrangements. Recent advances in biology, however, allow us to devise much more sophisticated models. We present a short survey of the existingwork on using biological constraints for genome rearrangements, and argue that a much more flexible approach is necessary to accompany the influx of newly available biological data.In this work we propose an extremely general framework for genome rearrangements with biological constraints. Our main contribution is a polynomial time algorithm that, for an arbitrary cost function, finds a minimum cost scenario among those of minimum length. Along the way we establish a number of novel links between sorting genomes with double cut and join rearrangements, sorting graphs with 2-breaks or edge swaps, sorting permutations with mathematical transpositions, sorting strings with interchanges, and token swapping on graphs
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Liu, Iris. "Comparative genome hybridization reveals widespread genome variation in pathogenic cryptococcus species." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/5646.
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Genome variability can influence the virulence of pathogenic microbes. The availability of
genome sequences for strains of the AIDS-associated fungal pathogens Cryptococcus
neoformans and C. gattii presented an opportunity to use Comparative Genome Hybridization
(CGH) to examine genome variability between strains of different molecular subtypes and
ploidy. CGH analysis of 15 strains revealed extensive genomic variation including regions of
difference (deletions and amplifications) and chromosome copy number variability. Although no
common genomic change was observed for these 15 strains, three key observations came out of
these studies. First, CGH identified putative recombination sites and the origins of specific
segments of the genome for the common laboratory strain, JEC21. Second, CGH and
subsequent PCR-RFLP (PCR-Restriction Fragment Length Polymorphism) analysis on 33
clinical, environmental and laboratory-generated AD hybrid strains revealed that chromosome 1
from the serotype A genome is preferentially retained in clinical strains. Third, CGH and
subsequent qRT-PCR (quantitative real-time PCR) analysis revealed disomy for chromosome 13
in two clinical strains: CBS7779 and WM626. Further qRT-PCR and phenotypic studies on
CBS7779 revealed a correlation between variable melanin production and disomy. Specifically,
highly melanized strains were monosomic for chromosome 13 and less melanized strains were
disomic for this chromosome. This correlation, however, only held for the initial CBS7779
isolates. That is, subsequent screens of highly-melanized and less-melanized isolates derived
from the initial CBS7779 strain no longer followed this pattern. These subsequent screens,
however, did reveal that 1) disomy, once established, was a relatively stable trait and 2) having
disomy at chromosome 13 seemed to increase the probability of developing disomy at
chromosome 4. Finally, qRT-PCR of 13 additional strains from AIDS patients revealed that
disomy of both chromosome 13 and chromosome 4 is common in freshly isolated, clinical
strains. Overall, the data presented in this thesis reveal novel aspects of genome variability and
lay the foundation for future studies on the relevance of variation in the virulence of C.
neoformans.
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Dewhurst, S. M. "Whole genome doubling propagates chromosomal instability and accelerates cancer genome evolution." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1473166/.
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Tetraploidy has long been proposed as an intermediate cellular stage en route to the aneuploidy and chromosomal instability that is observed in many cancer types. Although tetraploidy has been shown to be an unstable cellular state, an in depth analysis of the effect of a spontaneous tetraploidisation event on the cancer genome has not been carried out. Using an isogenic system of naturally occurring tetraploid cells derived from a chromosomally stable colorectal cancer cell line, the effect of tetraploidisation on genome stability over time was assessed. Tetraploid cells were shown to have increased structural and numerical instability on a per cell but not per chromosome basis. Over time the tetraploid genome became increasingly genomically unstable, which is likely due to the increased ability of tetraploid clones to propagate segregation errors. The genomic landscape of tetraploid clones began to recapitulate the genomic architecture of chromosomally unstable colorectal cancer, and allowed for the selection of clinically high risk chromosomal losses over time. Genome doubling was further shown to be a predictive marker of poor prognosis in colorectal cancer. Exhaustive analysis of DNA and mRNA failed to reveal any common changes in tetraploid clones that are likely to explain their aneuploidy tolerance phenotype. Instead a focussed siRNA screen of genes commonly mutated in genome-doubled tumours of multiple cancer types was carried out. Given the high-risk clinical phenotypes associated with tetraploidy and chromosomal instability, it remains a priority to identify the mechanisms allowing tumour cells to undergo tetraploidisation and to sustain chromosome segregation errors.
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Clouse, Jared William. "The Amaranth (Amaranthus Hypochondriacus) Genome: Genome, Transcriptome and Physical Map Assembly." BYU ScholarsArchive, 2015. https://scholarsarchive.byu.edu/etd/5916.
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Amaranthus hypochondriacus is an emerging pseudo-cereal native to the New World which has garnered increased attention in recent years due to its nutritional quality, in particular its seed protein, and more specifically its high levels of the essential amino acid lysine. It belongs to the Amaranthaceae family, is an ancient paleotetraploid that shows amphidiploid inheritance (2n=32), and has an estimated genome size of 466 Mb. Here we present a high-quality draft genome sequence of the grain amaranth A. hypochondriacus. The genome assembly consisted of 377 Mb in 3,518 scaffolds with an N50 of 371 kb. Repetitive element analysis predicted that 48% of the genome is comprised of repeat sequences, of which Copia-like elements were the most common classified retrotransposon. A transcriptome, consisting of 66,370 contigs, was assembled from eight different tissue and abiotic stress libraries. Annotation of the genome identified 23,059 genes that were supported by our de novo transcriptome assembly, the RefBeet 1.1 gene index and the Uniprot_sprot database. To describe the genetic diversity within the grain amaranths (A. hypochondriacus, A. caudatus, and A. cruentus) and their putative progenitor (A. hybridus) we re-sequenced seven accessions in the genus Amaranthus (four A. hypochondriacus, and one of each A. caudatus, A. cruentus, and A. hybridus), which identified 7,184,636 and 1,760,433 interspecific and intraspecific single nucleotide polymorphisms, respectively. A phylogeny analysis of the re-sequenced accessions substantiated the classification of A. hybridus as the progenitor species of the grain amaranths. Lastly, we generated a physical map for A. hypochondriacus using the BioNano optical mapping platform. The physical map spanned 340 Mb and a hybrid assembly using the BioNano optical genome maps nearly doubled the N50 of the assembly to 697 kb. Moreover, we analyzed synteny between amaranth and Beta vulgaris (sugar beet) and estimated, using Ks analysis, the age of the most recent polyploidization event in amaranth.
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Svedberg, Jesper. "Catching the Spore killers : Genomic conflict and genome evolution in Neurospora." Doctoral thesis, Uppsala universitet, Systematisk biologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-329498.
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A genome is shaped by many different forces. Recombination can for instance both create and maintain genetic diversity, but the need to locally reduce recombination rates will also leave specific signatures. Genetic elements can act selfishly and spreading at the expense of the rest of the genome can leave marks of their activity, as can mechanisms that suppresses them, in a phenomenon known as genomic conflict. In this thesis, I have studied the forces driving genome evolution, using modern genome sequencing techniques and with a special focus on a class of selfish genetic elements known as Spore killers found in the fungus Neurospora. First, we show novel findings on large-scale suppression of recombination by non-structural means in the N. tetrasperma genomes. In contrary, in the genomic region harbouring the spore killer elements Sk-2 and Sk-3 of N. intermedia, a dense set of inversions that are interspersed with transposable elements have accumulated. The inversions are unique for each killer type, showing that they have a long separated evolutionary history and likely have established themselves independently. For the Sk-2 haplotype, where we have polymorphism data, we see signs of relaxed selection, which is consistent with the hypothesis that recombination suppression reduces the efficacy of selection in this region. These results show the strong effects the divergent selective forces of genomic conflicts can have on chromosome architecture. Furthermore, we investigate the hypothesis that spore killing can drive reproductive isolation, by comparing the fertility of crosses between N. metzenbergii and either killer or non-killer N. intermedia strains. We show that crosses with spore killer strains have lower fertility, which cannot be explained by the killing itself, but is potentially caused by an incompatibility gene captured in the non-recombining region. Finally, we identified the genetic element responsible for causing spore killing in the Sk-1 spore killer strains found in N. sitophila. Unlike the Sk-2 and Sk-3 elements, Sk-1 is not connected to a large, non-recombining region, but is caused by a single locus, and we also find indications that this locus was introgressed from N. hispaniola.
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Tarabichi, Maxime. "Integrative analyses of genome-wide transcriptomic and genomic thyroid cancer profiles." Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/225138.
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Cette thèse en bioinformatique a été réalisée entre 2010 et 2015 dans le groupe du Pr. Vincent Detours à l’Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire. Nous avons analysé des données génomiques et transcriptomiques provenant de carcinomes papillaires de la thyroïde (CPTs) et leurs tissus non-cancéreux adjacents. La première partie étudiait les différences transcriptomiques entre CPTs post-Tchernobyl et CPTs sporadiques, et leur tissus non-cancéreux adjacents. Dans notre cohorte, les cas sporadiques étaient en moyenne et significativement un an plus jeunes. Après un ajustement des données transcriptionnelles pour l'âge, près de 400 gènes étaient plus exprimés dans les tissus adjacents des patients exposés aux radiations. Cependant, nous n’avons pu détecter aucune surreprésentation de groupe de gènes participant à des fonctions biologiques connues. Il était possible de distinguer les cas sporadiques des cas post-Tchernobyl sur base des transcriptomes de leurs tissus adjacents, avec une précision de ~70%. Cette surexpression de gènes dans les tissus non-cancéreux adjacents pourrait être liée à une radiosensibilité accrue dans le groupe des patients exposés aux radiations de Tchernobyl. Dans la deuxième étude, nous avons intégré des données provenant des patients de la première partie, incluant les nombres de copies d'ADN des CPTs, le génotype de plus de 400.000 SNPs dans le sang et les données transcriptionnelles des CPTs et leurs tissus non-cancéreux adjacents. En reproduisant les résultats d'une étude précédente, nous avons retrouvé la région 7q11.23 dupliquée exclusivement dans un tiers des patients exposés aux radiations. Dans une étude indépendante, un autre groupe a montré que la duplication de cette région était plus fréquente dans une population de lignées cellulaires radiosensibles que dans la population humaine normale. Cependant, en analysant les transcriptomes des patients présentant cette duplication, nous n'avons pas détecté de différence d’expression des gènes codés dans cette région génomique. En outre, aucun génotype de SNP n'était significativement lié à l'exposition aux radiations. En conclusion, les résultats confirment qu'un tiers des CPTs post-Tchernobyl ont des traces d'un dégât radio-sensibilsant dans leur ADN. Dans une troisième étude, nous avons étudié les différences transcriptionnelles entre CPTs et leurs métastases ganglionnaires (MGs) associées, ainsi qu'entre des CPTs développant des MGs (N+) et des CPTs ne développant pas de MGs (N0). Des études précédentes comparant les MGs et leurs tumeurs associées impliquant d’autres organes ont montré une surexpression de gènes dans les MGs, liés aux cellules immunitaires. Ce signal provient du tissu contaminant environnant les MGs. Pour se défaire de ce signal contaminant, d’autres études ont microdisséqué au laser les parties tumorales des MGs. Cependant, la microdissection retire aussi le stroma associé à la tumeur, alors que celui-ci est justement impliqué dans la progression tumorale. Grâce à une méthode originale, nous avons corrigé nos données d’expression des MGs pour leur contenu en contaminant ganglionnaire non-cancéreux. Après cette correction, l’expression de gènes liés au stroma était plus élevée dans les MGs que dans leurs CPTs. Les différences d’expression entre N0 et N+ n’étaient pas reproductibles entre 4 jeux de données indépendants de CPTs. Ceci démontre l’absence d’un signal transcriptionnelle lié au statut nodal dans ces données. Cependant, en utilisant des données publiques comprenant des centaines de tumeurs, il est possible de prédire le statut nodal (N0 ou N+) des CPTs ainsi que des cancers du sein et du colon à partir de leurs transcriptomes. Des études précédentes montraient des taux de prédiction presque parfaits (>90%) du statut nodal à partir des données transcriptomiques. Nous avons décelés dans ces études le même biais technique de sélection des gènes, qui peut expliquer ces taux artificiellement élevés. Dans notre étude, ce biais n’était pas présent et la précision de nos prédictions était limitée (<70%), questionnant l’intérêt clinique de telles prédictions. La présence d’un signal permettant de prédire le statut nodal et l’irreproductibilité de ce signal dans des jeux de données indépendants peuvent s'expliquer par l’association entre le statut nodal et des caractéristiques d'agressivité des tumeurs, qui pourraient, elles, avoir une influence reproductible sur les transcriptomes. Dans notre dernière étude, nous avons analysé les différences entre CPTs, liées à la présence de BRAFV600E, une mutation commune à 60% des CPTs. En utilisant un jeu de données public, nous avons montré que les CPTs présentant la mutation étaient plus dédifférenciés, et plus infiltrés en stroma, probablement en lymphocytes et fibroblastes; et que ces CPTs présentaient plus de fibrose et proliféraient sans doute plus. Tout ceci suggère que les CPTs mutés pour BRAF constituent un groupe de CPTs plus agressif. Des caractéristiques d’agressivité pourraient être détectées au front invasif, c’est-à-dire la périphérie de la tumeur définissant son contact avec le stroma, notamment la présence de regroupement de cellules isolées du reste de la tumeur. Dans les CPTs, ces îlots cellulaires isolés sont observés sur des lames histologiques 2D et pourraient être expliqués soit par un détachement cellulaire, signe d’agressivité lié au processus métastatique, soit une conformation complexe compatible avec une tumeur connexe en 3D. Dans un CPT, nous avons analysé la conformation 3D du front invasif d'un CPT muté. Nous avons reconstruit son volume 3D grâce à une méthode originale. Les groupes de cellules cancéreuses qui semblaient isolées sur les images 2D d’histopathologie, étaient en fait connectés en 3D. L’hypothèse de la présence de détachement cellulaire suite à la transition épithélio-mésenchymateuse n’est donc pas requise pour expliquer la présence de ces îlots cellulaires en 2D. La forme 3D du front invasif impliquait une surface de contact entre tumeur et stroma bien plus importante qu'impliquée par la forme ellipsoïde habituellement décrite. Les fibroblastes participaient autant à la création de la masse tumorale que les cellules cancéreuses, puisque ces deux groupes de cellules proliféraient à la même vitesse. A l'avenir, le séquençage du matériel génétique de cellules individuelles facilitera notre interprétation des signaux génomiques et transcriptomiques, qui jusqu’alors provenaient de tissu complet, i.e. un mélange de populations de cellules tumorales, stromales et de contaminant. Une signature de radiation pourrait être extraite des profils mutationnels de cellules individuelles exposées aux radiations et à l’H2O2 in vitro et comparée à la signature des CTPs post-Tchernobyl. Les cellules tumorales et stromales individuelles des MGs pourraient être comparées aux cellules tumorales et stromales invividuelles des CPTs. De même les cellules individuelles mutées pour BRAFV600E pourraient être comparées aux cellules non mutées.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
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Axelsson, Tomas. "Evolution of polyploid Brassica genomes : genome structure and the evolution of duplicated genes /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 2000. http://epsilon.slu.se/avh/2000/91-576-5768-8.pdf.
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Eldfjell, Yrin. "Identifying Mitochondrial Genomes in Draft Whole-Genome Shotgun Assemblies of Six Gymnosperm Species." Thesis, Stockholms universitet, Matematiska institutionen, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-175410.
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Sequencing efforts for gymnosperm genomes typically focus on nuclear and chloroplast DNA, with only three complete mitochondrial genomes published as of 2017. The availability of additional mitochondrial genomes would aid biological and evolutionary understanding of gymnosperms. Identifying mtDNA from existing whole genome sequencing (WGS) data (i.e. contigs) negates the need for additional experimental work but previous classification methods show limitations in sensitivity or accuracy, particularly in difficult cases. In this thesis I present a classification pipeline based on (1) kmer probability scoring and (2) SVM classification applied to the available contigs. Using this pipeline the mitochondrial genomes of six gymnosperm species were obtained: Abies sibirica, Gnetum gnemon, Juniperus communis, Picea abies, Pinus sylvestris and Taxus baccata. Cross-validation experiments showed a satisfying and forsome species excellent degree of accuracy.Vid sekvensering av gymnospermers arvsmassa har fokus oftast lagts på kärn- och kloroplast-DNA. Bara tre fullständiga mitokondriegenom har publicerats hittills (2017). Fler mitokondriegenom skulle kunna leda till nya kunskaper om gymnospermers biologi och evolution. Då mitokondriernas arvsmassa identifieras från tillgängliga sekvenser för hela organismen (så kallade “contiger”) behövs inget ytterligare laboratoriearbete, men detta förfarande har visat sig leda till bristfällig känslighet och korrekthet, särskilt i svåra fall. I denna avhandling presenterar jag en metod baserad på (1) kmer-sannolikheter och (2) SVM-klassificering applicerad på de tillgängliga contigerna. Med denna metod togs arvsmassan för mitokondrien hos sex gymnospermer fram: Abies sibirica, Gnetum gnemon, Juniperus communis, Picea abies, Pinus sylvestris och Taxus baccata. Korsvalideringsexperiment visade en tillfredställande och för vissa arter utmärkt precision.
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Tiwari, Jitesh. "Assembly and Automated Annotation of the Clostridium scatologenes Genome." TopSCHOLAR®, 2012. http://digitalcommons.wku.edu/theses/1175.
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Clostridium scatologenes is an anaerobic bacterium that demonstrates some unusual metabolic traits such as the production of 3-methyl indole. The availability of genome level sequencing has lent itself to the exploration and elucidation of unique metabolic pathways in other organisms such as Clostridium botulinum. The Clostridium scatologenes genome, with an estimated length 4.2 million bp, was sequenced by the Applied Biosystems Solid method and the Roche 454 pyrosequencing method. The resulting DNA sequences were combined and assembled into 8267 contigs with an average length of 1250 bp with the Newbler Assembler program. Comparision of published subunits of csd gene and assembled contigs identified that one contig contained all three subunits. In addition a gene with similarity to clostridium carboxidivorans butyrate kinase was found lined next to csd gene. An alignment of the contig and csdgene sequences identified three deletions in the contig within the 4066 bases of the alignment. This implies that there is about 0.07% error rate in the sequencing itself requiring more finishing.
Even without finishing the genome assembly into single contig, contigs were annotated in RAST pipeline predicting 2521 protein encoding genes (PEGs). The PEGs were classified by their metabolic function and compared to classified PEGs found in the closely related clostridium species, Clostridium carboxidivorans and Clostridium. ljungdahlii, which have similarly sized genomes. According to the RAST analysis, Clostridium scatologenes had 35% subsystem coverage of all known metabolic processes with its 2521 PEGs. This compares to 41% for Clostridium carboxidivorans with 4174 PEGs (29) and 42% for Clostridium ljungdahlii with 4184 PEGs (30), indicating that Clostridium scatologenesmay still have more genes to be identified. Comparison of the percent genes found in the metabolic subsystems was similar except in motility and chemotaxis.
The contigs, on which the csd gene and tryptophan metabolizing genes lay, were examined to see if additional genes might support these metabolic pathways. Butyrate kinase was associated with the csd genes but no other associations were found for the two tryptophan metabolizing genes. The tryptophan biosynthesis operon genes were all found on one contig (contig 6771) and were syntenic with other bacterial species.
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Paudel, Rajan. "An Investigation into the Evolution of Nucleotide Composition in the Human Genome." University of Toledo Health Science Campus / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=mco1564404055416097.
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Pacheco, Túlio Gomes. "The complete plastid genome sequence of Passiflora cincinnata: genome rearrangements, massive plastid gene losses and implications to genome-plastome incompatibility." Universidade Federal de Viçosa, 2016. http://www.locus.ufv.br/handle/123456789/11539.
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A organização, ordem e conteúdo gênico de genomas plastidiais (plastomas) são bastante conservados em angiospermas, porém há exceções a esta regra. Este parece ser o caso do gênero Passiflora, pois há evidências de perdas não usuais de genes plastidiais para espécies deste gênero. Porém, nenhum plastoma de Passiflora foi publicado até o momento, o que dificulta estudos a respeito da evolução do plastoma deste grupo. Da mesma forma, o estudo das causas da incompatibilidade entre o genoma nuclear e plastoma, apresentada por alguns híbridos interespecíficos de Passiflora, tem se mantido obscuro devido à falta de sequências plastidiais disponíveis no banco de dados. Assim, visando começar a preencher estas lacunas e ainda permitir a caracterização de marcadores genéticos plastidiais e a construção de vetores para transformação plastidial em Passiflora, o presente trabalho teve como objetivo o sequenciamento, montagem, análise e caracterização do plastoma de Passiflora cincinnata. Os dados indicam uma massiva perda de genes plastidiais essenciais para a viabilidade celular (infA, rps7, rps16, rpl20, rpl22, ycf1 e ycf2), os quais, muito provavelmente, foram transferidos para o núcleo e seus produtos são importados pelos plastídios. Este genoma mostrou alta taxa de substituição de nucleotídeos para os genes accD e clpP. Apesar da alta divergência, a sequência traduzida destes genes mantém a maioria dos domínios funcionais previstos para as proteínas que codificam e com isso a funcionalidade dos mesmos não pode ser descartada. Além disso, múltiplas inversões também foram detectadas no plastoma de P. cincinnata, mudando a ordem de vários genes. Em conjunto, os dados sugerem uma incomum evolução do plastoma de P. cincinnata, caracterizada por perdas gênicas, inversões no genoma e presença de genes com aceleradas taxas de substituição de nucleotídeos. Assim, é possível sugerir que esta instabilidade do genoma e perda de genes essenciais possa estar relacionada com a incompatibilidade entre núcleo e plastoma observada em híbridos de Passiflora. Por fim, a sequência completa do plastoma de P. cincinnata, obtida neste trabalho torna viável a transformação plastidial nesta espécie, visando aplicações biotecnológicas, além de estudos evolutivos e de genética funcional.
The plastid genome (plastome) organization, gene content and order is well conserved in most angiosperms, but there are some exceptions. The Passiflora genus is one of those exceptions, because there are evidences of some unusual plastid gene losses to species of this genus. However, none plastome of Passiflora has been published to date, making studies related to the evolution and putative high instability of plastome in this group difficult. In parallel, the study of the causes of nucleus-plastome incompatibility, observed in interspecific hybrids of Passiflora, has remained obscure due to the lack of plastid sequences in the database. In the context, starting to fill these gaps and to enable the characterization of plastid genetic markers and the construction of vectors for plastid transformation in Passiflora, the aim of the present study was the sequencing, assembly, analysis and characterization of complete P. cincinnata plastome. The data indicate a massive loss of plastid genes that are essential for cell viability (infA, rps7, rps16, rpl20, rpl22, ycf1 and ycf2), which very likely were functionally transferred to the nucleus and its products are imported into plastid. This genome also showed a high rate of nucleotide substitution in several genes, such as accD and clpP. Despite this high divergence, the translated amino acid sequences of these genes retain most of functional domains predicted indicating that they can still encode functional proteins. In addition, multiple inversions were detected in the P. cincinnata plastome, changing the order of several genes. Taken together, the data suggest a markedly uncommon evolution of P. cincinnata plastome, characterized for gene losses, multiple inversions and genes with accelerated nucleotide substitution rates. Thus, it is possible to suggest that the genomic instability and essential genes losses, observed here, may be related to the genome- plastome incompatibility observed in Passiflora hybrids. This relation can be established and investigated of an accurate manner with the sequencing of other Passiflora plastomes. Finally, the complete plastome sequence of P. cincinnata obtained in this work enables the plastid transformation to this species, aiming biotechnology applications and studies of evolution and functional genetics.
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th, pwanch@msu ac, and Phatthanaphong Wanchanthuek. "Comparative genomics to investigate genome function and adaptations in the newly sequenced Brachyspira hyodysenteriae and Brachyspira pilosicoli." Murdoch University, 2009. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20091023.115612.
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Brachyspira hyodysenteriae and Brachyspira pilosicoli are anaerobic intestinal spirochaetes that are the aetiological agents of swine dysentery and intestinal spirochaetosis, respectively. As part of this PhD study the genome sequence of B. hyodysenteriae strain WA1 and a near complete sequence of B. pilosicoli strain 95/1000 were obtained, and subjected to comparative genomic analysis. The B. hyodysenteriae genome consisted of a circular 3.0 Mb chromosome, and a 35,940 bp circular plasmid that has not previously been described. The incomplete genome of B. pilosicoli contained 4 scaffolds. There were 2,652 and 2,297 predicted ORFs in the B. hyodysenteriae and B. pilosicoli strains, respectively. Of the predicted ORFs, more had similarities to proteins of the enteric Clostridium species than they did to proteins of other spirochaetes. Many of these genes were associated with transport and metabolism, and they may have been gradually acquired through horizontal gene transfer in the environment of the large intestine.
A reconstruction of central metabolic pathways of the Brachyspira species identified a complete set of coding sequences for glycolysis, gluconeogenesis, a non-oxidative pentose phosphate pathway, nucleotide metabolism and a respiratory electron transport chain. A notable finding was the presence of rfb genes on the B. hyodysenteriae plasmid, and their apparent absence from B. pilosicoli. As these genes are involved in rhamnose biosynthesis it is likely that the composition of the B. hyodysenteriae lipooligosaccharide O-sugars is different from that of B. pilosicoli. O-antigen differences in these related species could be associated with differences in their specific niches, and/or with their disease specificity. Overall, comparison of B. hyodysenteriae and B. pilosicoli protein content and analysis of their central metabolic pathways showed that they have diverged markedly from other spirochaetes in the process of adapting to their habitat in the large intestine.
The presence of overlapping genes in the two spirochaetes and in other spirochaete species also was investigated. The number of overlapping genes in the 12 spirochaete genomes examined ranged from 11-45%. Of these, 80% were unidirectional. Overlapping genes were found irregularly distributed within the Brachyspira genomes such that 70-80% of them occurred on the same strand (unidirectional, ->->/<-<-), with 16-28% occurring on opposite DNA strands (divergent, <-->). The remaining 4-6% of overlapping genes were convergent (-><-). The majority of the unidirectional overlap regions were relatively short, with >50% of the total observations overlapping by >4 bp. A small number of overlapping gene-pairs were duplicated within each genome and there were some triplet overlapping genes. Unique orthologous overlapping genes were identified within the various spirochaete genera. Over 75% of the overlapping genes in the Brachyspira species were in the same or related metabolic pathway. This finding suggests that overlapping genes are not only likely to be the result of functional constraints but also are constrained from a metabolomic context. Of the remaining 25% overlapping genes, 50% contained one hypothetical gene with unknown function. In addition, in one of the orthologous overlapping genes in the Brachyspira species, a promoter was shared, indicating the presence of a novel class of overlapping gene operon in these intestinal spirochaetes.
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Mok, Kwai-lung. "Computational discovery of cis-regulatory modules in human genome by genome comparison." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/b40203621.
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Mok, Kwai-lung, and 莫貴龍. "Computational discovery of cis-regulatory modules in human genome by genome comparison." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40203621.
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Rand, Vikki. "Genome evolution : a study of MHC paralogous genes in the human genome." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615641.
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Mollon, Jennifer. "Statistical analysis of genome-genome interaction with reference to kidney transplant outcome." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/statistical-analysis-of-genomegenome-interaction-with-reference-to-kidney-transplant-outcome(581ae9b3-83b5-4d13-985f-2c57a248bc07).html.
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Though widely believed to exist, few convincing examples of genetic interactions have been detected through statistical approaches in genome-wide association studies. The first piece of work in this thesis attempts to determine if there is evidence for the existence of such interactions within genes identified through protein-protein interactions. A software package is developed and applied to data from a recent publically available genetic study. No evidence was found for an enrichment of such interactions in the available data. The second study applies three current methods for interaction detection to a real data set with compelling evidence of an interaction. Sparse Partitioning, SNPHarvester and Random Jungle were selected, with the later two being followed by the HyperLasso as a post-processing step. Only one method, SNPHarvester, was able to detect the interaction. The third study outlines a local pilot project in renal transplant dysfunction. Genetic variants from donors and recipients are examined using survival analysis. Interactions between the two genomes are tested for an effect on the survival time of the kidney. Secondary renal phenotypes of acute rejection and progression to end-stage renal failure are also considered. There were no strongly significant associations discovered in this data. The final study is a multi-centre renal transplant study analysing over 2000 donor recipient pairs throughout the UK and Ireland. Although much larger than the pilot, this study also failed to detect any associations with graft survival time or the secondary phenotypes. SNPHarvester was applied to the data and there are some indications of potential interactions, but replication is essential before the results can be trusted. An outline of an extension to SNPHarvester to better handle survival data is presented. Results from all of these studies were largely negative. Detecting interactions in genome-wide data remains a difficult task. Narrowing the search space by filtering may be a better approach than attempting a genome-wide search, though SNPHarvester has proven to be useful and is a good choice if a true genome-wide search is required.
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Santana, Inês Manuela do Vale. "Proteotoxic stress in human genome stability." Master's thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12606.
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Mestrado em Biologia Molecular e CelularIncorporation of errors during protein synthesis is denominated mistranslation. This compromises the acquisition of a correct final three dimensional structure and consequently the accumulation in the cell of proteins with abnormal conformations. Cells have protein quality control (PQC) mechanisms to counteract the accumulation of aberrant proteins, but when these systems are overloaded proteins aggregate, generating proteotoxic stress. Mistranslation is associated with several diseases and with genomic alterations in yeast that increase adaptation potential. In this work, HEK293 cells were transfected with mutated tRNAs that misincorporate serine at various non-cognate codon sites. For this, a serine tRNAAGA was mutated in the anticodon and transfected into the HEK293 cells, creating five different cell lines that incorporate serine at Ala, Leu, Val, and His codons; one line was transfected with an empty plasmid (Mock). These cell lines were studied by flow cytometry and flourescence microscopy in order to evaluate their viability, proliferation, DNA content and micronuclei accumulation. The results show that mistranslation induced by these tRNAs does not affect the cellular viability but may promote minor DNA alterations. Also, cellular proliferation was compromised in some cell lines, namely in the cell line that misincorporates serine at leucine codons. In this cell line, the cell cycle was arrested in S or G2/M phases. Regarding micronuclei formation, a slight increase was seen in alanine and leucine cell lines. This cellular model allowed us to investigate the effect of low level of mistranslation on the genome of human cells and showed that human cells are highly resistant to the accumulation of aberrant proteins.
A introdução de erros durante a síntese proteica é um processo denominado mistranslation, do qual resulta a incorporação errónea de aminoácidos na proteína. Este processo compromete a aquisição da estrutura final correcta das proteínas e consequentemente a sua acumulação. As células apresentam mecanismos de controlo de qualidade de proteínas (PQC) que contrariam esta acumulação mas, se sobrecarregados, as proteínas podem agregar umas com as outras provocando danos nas células. A mistranslation está associada com vários efeitos tóxicos e diversas doenças. Recentemente, a mistranslation foi associada com alterações no genoma da levedura, que aumentam a sua capacidade adaptativa. Neste trabalho, células HEK293 foram transfectadas com tRNAs mutados para demonstrar como o processo de mistranslation afecta o genoma das células. Para tal, um tRNAAGA de serina foi mutado no anticodão e transfectado nas células, criando cinco linhas celulares diferentes que incorporam serina em codões de Ala, Leu, Val, e His. Foi também construída uma linha contendo um plasmídeo vazio (Mock). As linhas celulares criadas foram estudadas por citometria de fluxo e microscopia de flourescência, de modo a avaliar a viabilidade e proliferação celular, o conteúdo em DNA e a acumulação de micronúcleos. Os resultados mostram que o nível de mistranslation provocado nas células não afecta a viabilidade celular mas pode provocar algumas alterações no DNA. A proliferação celular foi afectada na linha celular que incorpora serina em codões de leucina, se observou uma paragem do ciclo celular nas fases S ou G2/M. Em relação aos micronúcleos, verificou-se um ligeiro aumento nas linhas celulares que incorporam serina em codões de alanina e leucina. Este modelo de estudo permitiu entender os efeitos dos níveis de mistranslation no genoma de células humanas e mostrar que estas células são bastante resistentes à acumulação de proteínas aberrantes.
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Alekseyev, Max. "Duplications and genome rearrangements." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3275933.
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Thesis (Ph. D.)--University of California, San Diego, 2007.Title from first page of PDF file (viewed October 3, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 81-87).
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Song, Weining. "Genome studies of cereals /." Title page, contents and summary only, 1992. http://web4.library.adelaide.edu.au/theses/09PH/09phs6984.pdf.
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Will, Jacqueline Ann Kennedy. "Genome analysis in Lolium." Thesis, Aberystwyth University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.344086.
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Costantini, Maria. "Genome organization in sponges." Thesis, Open University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397996.
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Brown, Charles Titus Sternberg Paul W. Davidson Eric H. "Tackling the regulatory genome /." Diss., Pasadena, Calif. : California Institute of Technology, 2007. http://resolver.caltech.edu/CaltechETD:etd-12192006-100331.
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Gretzinger, Harold Alex. "Christ, the final genome." Online full text .pdf document, available to Fuller patrons only, 2002. http://www.tren.com.
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Hannoush, Khodor. "Dynamic Pan-genome graphs." Electronic Thesis or Diss., Université de Rennes (2023-....), 2024. https://ged.univ-rennes1.fr/nuxeo/site/esupversions/046f12e6-165c-4827-8722-1639b95ea781.
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Les progrès rapides des technologies de séquençage ont révolutionné la génomique, conduisant à des bases de données génomiques massives et à des milliers de génomes assemblés. Cette croissance exponentielle des données a mis en évidence les limites des modèles traditionnels basés sur des références et a motivé le développement de représentations pan-génomiques qui reflètent la diversité des espèces. Parmi ces représentations, les graphes de de Bruijn compactés (cDBG) constituent une approche de pointe pour le stockage et les requêtes sur les grands ensembles de données génomiques. En regroupant les séquences redondantes et en représentant efficacement les chevauchements des k-mères, les cDBG minimisent la mémoire et le coût de calcul. Cependant, l'ajout de nouveaux génomes sur le cDBG pose des problèmes en raison de la nature statique de la plupart structures de données basées sur des cDBG, qui nécessitent souvent une reconstruction complète, ce qui les rend coûteux et inefficaces. Pour relever le défi de l'ajout de séquences, des méthodes permettant des mises à jour dynamiques des cDBG sans reconstruction complète sont nécessaires. Cette thèse présente, Cdbgtricks, une méthode de mise à jour d'un cDBG et de son index en ciblant les régions du graphe qui doivent être modifiées. En utilisant l'index mis à jour, Cdbgtricks permet de requêter une séquence et de rapporter les positions de ses k-mères dans le graphe, avec la possibilité de requêter des millions de séquencesThe rapid advancements in sequencing technologies have revolutionized genomics, leading to massive genomic databases and thousands of assembled genomes. This exponential growth of data exposed the limitations of traditional reference-based models and motivated the development of pan-genomic representations that reflect species diversity. Among these, compacted de Bruijn graphs (cDBGs) are a cutting-edge approach for storing and querying large genomic datasets. By collapsing redundant sequences and efficiently representing k-mer overlaps, cDBGs minimize memory and computational overhead. However, adding new genomes to a cDBG creates challenges due to the static nature of most cDBG data structures, which often require complete reconstruction, making them costly and inefficient. To address the challenge of adding sequences, methods that allow dynamic updates of cDBGs without full reconstruction are needed. This thesis presents, Cdbgtricks, a method for updating a cDBG and its index by targeting the regions in the graph that needs to be updated. Using the updated index, Cdbgtricks enables querying a sequence and reporting the positions of its k-mers in the graph, with the ability to query millions of sequences
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Ozato, Junior Tadaiti [UNESP]. "Complementação do seqüenciamento do genoma do Southern bean mosaic virus, isolado São Paulo, expressão da porção C-terminal da polimerase e produção de anti-soro policlonal." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/92490.
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O presente trabalho consistiu no seqüenciamento e caracterização molecular das Cadeias Abertas de Leitura (Open Reading Frames - ORFs) 2 e 3 do genoma do isolado São Paulo do Southern bean mosaic virus (SBMV-SP), completando-se o seqüenciamento de todo o genoma desse isolado. A ORF 2 codifica uma poliproteína (serino protease – VPg – RNA polimerase RNA-dependente) e a ORF 3 um produto com função desconhecida. O seqüenciamento da ORF 2 apresentou 2889 nucleotídeos, incluindo-se o códon de terminação UGA, com 962 aminoácidos deduzidos e massa molecular estimada de aproximadamente 105 kDa. Dentro da ORF 2, localiza-se a ORF 3 contendo 398 nucleotídeos, incluindo-se o códon de terminação UAA, com 132 aminoácidos e massa molecular estimada de aproximadamente 15 KDa. A análise feita a partir das seqüências das ORFS 2 e 3 do genoma do SBMV-SP, quando comparadas com outras espécies do mesmo gênero e isolados do SBMV, depositadas no GenBank, mostrou que a ORF 2 apresenta maior identidade (91,4% na seqüência de nucleotídeos e 95,0% na seqüência de aminoácidos deduzidos) com o isolado de Arkansas. Resultado similar foi obtido em relação à ORF 3 com valores de identidade de 97,0% tanto para as seqüências de nucleotídeos e aminoácidos deduzidos. Dados de filogenia corroboram os dados de identidade. Regiões conservadas do gênero Sobemovirus também foram identificadas, tais como Sítio de Ligação à Capa Protéica (CBPS), a tríade catalítica da serino protease (H-D-S) e a seqüência de heptanucleotídeos (TTTAAAC). A expressão em Escherichia coli da porção C-terminal da RNA Polimerase RNA Dependente (RpRd) produziu uma proteína de fusão de aproximadamente 67 kDa no sistema pMAL c2-x e de 30 kDa no sistema pET 28a. Quando a proteína de fusão foi injetada em coelhos houve a produção de anti-soro específico para a proteína recombinante.
The present work consisted of the sequencing and molecular characterization of the Open Reading Frames (ORFs) 2 and 3 from the São Paulo isolate genome of Southern bean mosaic virus (SBMV-SP), completing the sequencing of all the genome of this isolate. The ORF 2 encodes a polyprotein (serine protease - VPg - RNA dependent RNA polimarase) and the ORF 3 one product with unknown function. The sequencing of the ORF 2 reveals 2889 nucleotides, including the stop codon (UGA), with 962 deduced amino acids e and estimated molecular weight of approximately 105 kDa. Nested in the ORF 2 were found the ORF 3 with 398 nucleotides, including the stop codon (UAA), with 132 deduced amino acids and estimated molecular weight of approximately 15 kDa. The analysis made from the sequences of the ORFs 2 and 3 from the SBMV-SP genome, when compared with other species of the same gender and isolates of SBMV, deposited in the GenBank, showed that the ORF 2 presents higher identity (91,4% in the nucleotide sequence and 95,0% in the deduced amino acids sequence) with Arkansas isolate. Similar result was obtained in relation to the ORF 3 with identity values of 97,0% for the nucleotides and deduced amino acids sequences. Phylogeny data corroborate the identity data. Conserved regions of the Sobemovirus gender had also been identified such as Coat Protein Binding Site (CPBS), serine protease catalytic triad (H-D-S) and heptanucleotide sequence (TTTAAAC). The Expression in Escherichia coli of the C-terminal region of the RNA dependent RNA polimerase produced a fusion protein of approximately 67 kDa in pMAL c2-x system and a 30 kDa protein in pET 28a system. When the fusion protein ...(Complete abstract click electronic access below)
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鄭啓航 and Kai-hong Cheng. "Further development of the visual genome explorer: a visual genomic comparative tool." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B3122412X.
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Oliveira, Matheus Brito de. "GATOOL - Genome Assembly Tool: uma ferramenta web para montagem de genomas bacterianos." Universidade Estadual de Feira de Santana, 2017. http://localhost:8080/tede/handle/tede/513.
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The assembly of bacterial genomes consists of a process of reordering fragments so that the original genome can be represented. However, to maximize the results of genome assembly, some steps are required, for instance, read quality analysis and preprocessing, repetition identification and quality check. The process of assembly of genomes is a complex step that involves the type of sequencing that was used, there are several types of sequencers which imply different characteristics for each one for example: fragments size, throughput, among others. Analyzing these characteristics requires the use of several computational tools, to assist in all the processes mentioned above, and since the range of software available is quite broad and distinct, it is necessary for the user to learn to work with this computational diversity, dominating often knowledge that is not of the biological area, implying in less time for a deepening in biological questions. Based on this context, we developed a pipeline to perform an automated fragment analysis, read preprocessing, genome assembly and orientation of contigs, having as the assembly the main objective of the pipeline and that it will be managed by a Web application called GATOOL (Genome Assembly Tool). Aiming to evaluate the performance of the application, tests were carried out with two samples of prokaryotic organisms, which are: Bacillus amyloliquefaciens and Serratia marcescens. Also perform a test with seven SRA samples. Both organisms are sequenced on the Ion PGMTM platform. The tools used to perform the assembly were SPAdes and Velvet, both assemblers use de Bruijn graph algorithm as a paradigm for the assembly of the genome, after this stage the resulting set of contigs was ordered through the CONTIGuator, which is a reference ordering. We observed that the interface GATOOL allowed a quick and easy execution of several steps and processes in the field of genome assembly, including the assembly of two prokaryotic species in an automated way, thus facilitating the use and accomplishment of such processes by any user.
A montagem de genomas bacterianos ? um processo de reordena??o de fragmentos, de forma que se possa representar o genoma original. Entretanto, para que a montagem de um genoma seja realizada visando maximizar os resultados, ? preciso que algumas etapas sejam cumpridas, por exemplo: a an?lise dos fragmentos, o pr?-processamento destes fragmentos e novamente uma repeti??o do processo de an?lise, para verificar a efic?cia do pr?-processamento realizado. O processo de montagem de genomas ? uma etapa complexa, que envolve o tipo de sequenciamento que foi utilizado. Existem diversos tipos de sequenciadores, o que implica caracter?sticas distintas em cada um, como por exemplo: tamanho dos fragmentos, quantidade de fragmentos gerados por corrida, dentre outros. Analisando essas caracter?sticas, faz-se necess?ria a utiliza??o de diversas ferramentas computacionais para auxiliar a todos os processos citados anteriormente e, como a gama de softwares dispon?veis ? bem ampla e distinta, ? importante que o usu?rio domine essa diversidade computacional, contendo muitas vezes conhecimentos que n?o s?o da ?rea biol?gica, implicando menos tempo para um aprofundamento das quest?es biol?gicas. Com base neste contexto, prop?em-se um pipeline para a realiza??o da an?lise de fragmentos, pr?-processamento dos fragmentos, montagem de genomas e orienta??o de contigs, tendo como a montagem o objetivo principal do pipeline e este ser? gerenciado por uma aplica??o web chamada GATOOL (Genome Assembly Tool). Visando avaliar o desempenho da aplica??o, foram feitos testes com duas amostras de organismos procariontes, que s?o: Bacillus amyloliquefaciens e Serratia marcescens. Tamb?m foram realizados testes com sete amostras SRA. Ambos os organismos est?o sequenciados na plataforma Ion PGMTM. Os montadores usados foram o SPAdes e o Velvet, ambos montadores, utilizam o algor?tmo grafo de Bruijn como paradigma para a montagem do genoma; ap?s esta etapa, o conjunto de contigs resultante foi ordenado atrav?s do CONTIGuator, que ? uma ordena??o por refer?ncia. Observamos que a interface GATOOL permitiu uma execu??o r?pida e f?cil de diversas etapas e processos no campo da montagem de genomas, inclusive realizando a montagem de duas esp?cies procariontes de maneira automatizada, facilitando assim a utiliza??o e realiza??o de tais processos por qualquer usu?rio.
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Sharman, Joanna Louise. "Visualising Plasmodium falciparum functional genomic data in MaGnET : malaria genome exploration tool." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/5936.
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Malaria affects the lives of 500 million people around the world each year. The disease is caused by protozoan parasites of the genus Plasmodium, whose ability to evade the immune system and quickly evolve resistance to drugs poses a major challenge for disease control. The results of several Plasmodium genome sequencing projects have revealed how little is known about the function of their genes (over half of the approximately 5400 genes in Plasmodium falciparum, the most deadly human parasite, are annotated as hypothetical ). Recently, several large-scale studies have attempted to shed light on the processes in which genes are involved; for example, the use of DNA microarrays to profile the parasite s gene expression. With the emergence of varied types of functional genomic data comes a need for effective tools that allow biologists (and bioinformaticians) to explore these data. The goal of exploration/browsing-style analyses will typically be to derive clues towards the function of thus far uncharacterised gene products, and to formulate experimentally testable hypotheses. Graphic interfaces to individual data sets are obviously beneficial in this endeavour. However, effective visual data exploration requires also that interfaces to different functional genomic data are integrated and that the user can carry forward a selected group of genes (not merely one at a time) across a variety of data sets. Non-expert users especially benefit from workbenchlike tools offering access to the data in this way. Still, only very few of the contemporary publicly available software have implemented such functionality. This work introduces a novel software tool for the integrated visualisation of functional genomic data relating to P. falciparum: the Malaria Genome Exploration Tool (MaGnET). MaGnET consists of a light-weight Java program for effective visualisation linked to a MySQL database for data storage. In order to maximise accessibility, the program is publicly available over the World Wide Web (http://www.malariagenomeexplorer.org/). MaGnET incorporates a Genome Viewer for visualising the location of genomic features, a Protein-Protein Interaction Viewer for visualising networks of experimentally determined interactions and an Expression Data Viewer for displaying mRNA and protein expression data. Complex database queries can easily be constructed in the Data Analysis Viewer. An advantage over most other tools is that all sections are fully integrated, allowing users to carry selected groups of genes across different datasets. Furthermore, MaGnET provides useful advanced visualisation features, including mapping of expression data onto genomic location or protein-protein interaction network. The inclusion of available third-party Java software has expanded the visualisation capability of MaGnET; for example, the Jmol viewer has been incorporated for viewing 3-D protein structures. An effort has been made to only include data in MaGnET that is at least of reasonable quality. The MaGnET database collates experimental data from various public Plasmodium resources (e.g. PlasmoDB) and from published functional genomic studies, such as DNA microarrays. In addition, through careful filtering and labelling we have been able to include some predicted annotation that has not been experimentally confirmed, such as Gene Ontology and InterPro functional assignments and modelled protein structures. The application of MaGnET to malaria biology is demonstrated through a series of small studies. Initial examples show how MaGnET can be used to effectively demonstrate results from previously published analyses. This is followed up by using MaGnET to make a set of predictions about the possible functions of selected uncharacterised genes and suggesting follow-up experiments.
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Dumitriu, Alexandra. "Genome-wide expression and genomic data integration analyses in sporadic Parkinson disease." Thesis, Boston University, 2012. https://hdl.handle.net/2144/31542.
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Thesis (Ph.D.)--Boston UniversityParkinson disease (PD) is the second most common neurodegenerative disorder, affecting an estimated 2% of the population above 65 years of age. Although familial forms of PD have been linked to specific mutations responsible for the onset of the disease, the majority of PD cases is still of unknown etiology. PD has been traditionally studied using individual genetic methods, such as linkage analysis, genome-wide association (GWAS), or microarray expression studies. Nevertheless, the intrinsic disease genetic variability, and the unilateral analysis approach of available datasets made the detection of robust gene or pathway signals difficult. Studies of PD that combine a range of systems genetics approaches, and integrate complementary disease-relevant genetic datasets, represent a promising approach for accommodating prior inconsistent, as well as diverse results. To investigate the genetics of idiopathic PD, I performed the largest genome-wide expression study in brain tissue to date. The study was carried out on the 1-color Agilent 60-mer Whole Human Genome Microarray, and included 26 neurologically healthy control and 27 PD samples from the frontal cortex Brodmann 9 area (BA9). The selected brain samples were of high quality (high pH and RNA integrity, no significant signs of Alzheimer disease pathology), and had rich documentation of neuropathological and clinical information available. I analyzed the microarray expression results in combination with genotyping data for PD-associated single nucleotide polymorphisms obtained for the microarray brain samples, and detected a pathway of interest for PD involving the FOXO1 (Forkhead box protein O1) gene. This result was verified in additional publically available expression datasets. I then performed a network-based canonical pathway analysis of PD, combining results from available GWAS, microarray expression, and animal model expression studies. The used analysis framework was a human functional-linkage network (FLN), consisting of genes as nodes, and weighted links indicating the confidence of gene-pair involvement in similar biological processes. I demonstrated the relevance of the used FLN for studying PD. Additionally, I ranked genes and pathways based on the available disease datasets. The frontal cortex BA9 study, and an additional non-PD microarray study were used as the positive and negative controls, respectively, for the obtained results.