Dissertations / Theses on the topic 'Comparative genomics'
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Loman, Nicholas James. "Comparative bacterial genomics." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/2839/.
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For the most part, diagnostic clinical microbiology still relies on 19th century ideas and techniques, particularly microscopy and laboratory culture. In this thesis I investigate the utility of a new approach, whole-genome sequencing (WGS), to tackle current issues in infectious disease. I present four studies. The first demonstrates the utility of WGS in a hospital outbreak of Acinetobacter baumannii. The second study uses WGS to examine the evolution of drug resistance following antibiotic treatment. I then explore the use of WGS prospectively during an international outbreak of food-borne Escherichia coli infection, which caused over 50 deaths. The final study compares the performance of benchtop sequencers applied to the genome of this outbreak strain and touches on the issue of whether WGS is ready for routine use by clinical and public health laboratories. In conclusion, through this programme of work, I provide ample evidence that whole-genome sequencing of bacterial pathogens has great potential in clinical and public health microbiology. However, a number of technical and logistical challenges have yet to be addressed before such approaches can become routine.
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Axelsson, Erik. "Comparative Genomics in Birds." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7432.
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Eriksen, Niklas. "Combinatorial methods in comparative genomics." Doctoral thesis, KTH, Mathematics, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3508.
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Manee, Manee. "Comparative genomics of noncoding DNA." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/comparative-genomics-of-noncoding-dna(d16aa46c-b8a2-4e6c-b825-d4246d3775fa).html.
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High levels of primary sequence conservation are observed in many noncoding regions of eukaryotic genomes. These conserved noncoding elements (CNEs) have shown to be robust indicators of functionally constrained elements. Nevertheless, the function of only a small fraction of such CNEs is known and their role in genome biology remains largely a mystery. Comparative genomics analysis in model organisms can shed light on CNE function and evolution of noncoding DNA in general. Recently, it has been reported that short CNEs in the Drosophila genome are typically very AT-rich but have unusually high levels of GC content in a much larger (~500 bp) window around them. To understand whether these "side effects" are dependent on their CNE definition or are a more general feature of the Drosophila genome, we analysed base composition of CNEs from two different CNE detection methods. We found side effects are real, but are restricted to a subset of CNEs in the genome. An alternative hypothesis to explain the existence of CNEs is the mutational cold spot hypothesis. Previous work using SNPs was shown evidence that CNEs are not mutational cold spots. Here, non-reference transposable elements (TEs) were used to test cold spot hypothesis. A significant reduction in levels of non-reference TEs was found in intronic and intergenic CNEs compared to the expected number of insertions. TEs in intergenic CNEs were also found at lower allele frequencies than TEs in intergenic spacers. Furthermore, we used simulation to explore the effects of insertion/deletion (indel) evolution on noncoding DNA sequences with and without constrained noncoding elements. We assessed several indel-capable simulators to test expected outcomes with no selectively constrained elements. Simulations with constrained elements show that sequences grow in length even when the deletion rate is exactly the same as the insertion rate. This result can be interpreted as being due to purifying selection on CNEs acting to remove an excess of deletion over insertions. Together, the results presented here provide insights into the evolution of noncoding DNA in one of the most important model organisms.
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Mikkelsen, Tarjei Sigurd 1978. "Mammalian comparative genomics and epigenomics." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/52808.
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Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student submitted PDF version of thesis.
Includes bibliographical references.
The human genome sequence can be thought of as an instruction manual for our species, written and rewritten over more than a billion of years of evolution. Taking a complete inventory of our genome, dissecting its genes and their functional components, and elucidating how these genes are selectively used to establish and maintain cell types with markedly different behaviors, are key challenges of modern biology. In this thesis we present contributions to our understanding of the structure, function and evolution of the human genome. We rely on two complementary approaches. First, we study signatures of evolutionary processes that have acted on the genome using comparative sequence analysis. We generate high quality draft genome sequences of the chimpanzee, the dog and the opossum. These species share a last common ancestor with humans approximately 6 million, 80 million and 140 million years ago, respectively, and therefore provide distinct perspectives on our evolutionary history. We apply computational methods to explore the functional organization of the genome and to identify genes that contribute to shared and species-specific traits. Second, we study how the genome is bound by proteins and packaged into chromatin in distinct cell types. We develop new methods to map protein-DNA interactions and DNA methylation using single-molecule based sequencing technology. We apply these methods to identify new functional sequence elements based on characteristic chromatin signatures, and to explore the relationship between DNA sequence, chromatin and cellular state.
by Tarjei Sigurd Mikkelsen.
Ph.D.
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Ryder, Carol D. "Comparative genomics of Brassica oleracea." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/51651/.
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The scientific case made by the AUTHOR’S comparative Brassica oleracea genomics work is presented through 5 peer reviewed research papers. In order to achieve a comprehensive understanding of the evolution of B. oleracea the identification of unique genome characteristics, established using comparative genomics, is required. The genome characteristics established within these papers deliver significant contributions to original knowledge. These include a detailed illustration of how macro scale synteny varies markedly between the B. oleracea and A. thaliana genomes; unambiguous integration of the B. oleracea cytogenetic and genetic linkage maps; a cross species characterisation of a large collinear inverted segmental duplication on a single B. oleracea chromosome establishing that the relative physical distances have stayed approximately the same; retrotransposon copy number estimations and characterisation of their genomic organisation and isolation, characterisation and cross species analysis of a C genome specific repeat. For each paper the AUTHOR’S individual scientific contribution to each aspect of the work is described in detail. Both individually and as a body of work these publications substantially advance the fields of comparative, Brassica and genomic research.
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Dong, Xin. "Comparative genomics of rickettsia species." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM5054/document.
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Le genre Rickettsia, sont des petites bactéries Gram-négatives et symbiotes intracellulaires obligatoires des eucaryotes. Les Rickettsia sont surtout connus pour leur pathogénicité et pour provoquer des maladies graves chez l'homme et les autres animaux. À ce jour, 26 espèces valides de Rickettsies ont été identifiées dans le monde entier, dont 20 sont des agents pathogènes éprouvées. Toutes les espèces de Rickettsies validées sont associées à des arthropodes. Les phylogénies basées sur divers marqueurs moléculaires ont présenté des topologies discordantes, avec seulement R. bellii et R. canadensis qui ne sont classées ni parmi la fièvre boutonneuse groupe rickettsies, ni parmi le typhus groupe rickettsies. En utilisant les méthodes avancées de séquençage de génomes entiers, nous avons obtenu et analysé quatre séquences génomiques de Rickettsies : R. helvetica, R. honei, R. australis et R. japonica. Via la phylogénomique qui constitue une nouvelle stratégie permettant de mieux comprendre leur évolution, l'on remarque que ces micro-organismes ont subi une évolution génomique réduite au cours de spécialisation en intracellulaire. Plusieurs caractéristiques évolutives, comme le réarrangement des gènes, la réduction génomique, le transfert horizontal de gènes et l'acquisition d'ADN égoïste, ont formé les génomes Rickettsia d'aujourd'hui. Ces processus peuvent jouer un rôle important pour équilibrer la taille du génome afin de l'adapter au mode de vie intracellulaire. En outre, la pathogénicité des rickettsies peut être associée à la réduction génomiqueThe Rickettsia genus is composed of small, Gram-negative, bacteria that are obligate intracellular eukaryotic symbionts. Members of the genus Rickettsia are best known for infecting and causing severe diseases in humans and other animals. To date, 26 valid Rickettsia species have been identified worldwide, including 20 that are proven pathogens. All validated Rickettsia species are associated to arthropods that act as vectors and/or reservoirs. The phylogenies based on various molecular markers have resulted in discrepant topologies, with R. bellii and R. canadensis being classified neither among spotted fever nor typhus group rickettsiae. In this thesis, using the advanced whole genomic sequencing methods, we have and analyzed the genomic sequences from four Rickettsia species, including R. helvetica, R. honei, R. australis and R. japonica. Phylogenomics constitute a new strategy to better understand their evolution. These microorganisms underwent a reductive genomic evolution during their specialization to their intracellular lifestyle. Several evolutive characteristics, such as gene rearrangement, reduction, horizontal gene transfer and aquisition of selfish DNA, have shaped Rickettsia genomes. These processes may play an important role in free-living bacteria for balancing the size of genome in order to adapt the intracellular life style. In addition, in contrast with the concept of bacteria becoming pathogens by acquisition of virulence factors, rickettsial pathogenecity may be linked to genomic reduction of metabolism and regulation pathways
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Sentausa, Erwin. "Intraspecies comparative genomics of Rickettsia." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5082/document.
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Le genre Rickettsia est composé de bactéries Gram-négatives, intracellulaires obligatoires qui causent un éventail de maladies humaines à travers le monde. Des nouvelles techniques ont permis de progresser dans l'identification et la classification des Rickettsia, y compris l'introduction de méthodes moléculaires comme la comparaison de séquences de gènes (ARNr 16S, ompA, ompB, gltA, sca4 …) et la création du statut de sous-espèce. La génomique et les techniques de séquençage de nouvelle génération ont permis d’accéder à une nouvelle façon d’en apprendre davantage sur la pathogenèse et l'évolution de Rickettsia. La première partie de cette thèse est une revue sur les avantages et les limites de la génomique en taxonomie des procaryotes, tandis que la seconde partie est constituée des analyses génomiques de cinq sous-espèces de Rickettsia et une nouvelle espèce de Rickettsia. En utilisant des méthodes de séquençage à haut débit, nous avons obtenu les génomes de R. sibirica sibirica, R. sibirica mongolitimonae, R. conorii indica, R. conorii caspia, R. conorii israelensis et R. gravesii. Ce travail constitue la base d’autres études qui permettront de mieux comprendre les mécanismes physiopathologiques, l’évolution, et la taxonomie des rickettsiesThe Rickettsia genus is composed of Gram-negative, obligate intracellular bacteria that cause a range of human diseases around the world. New techniques have led to progress in the identification and classification of Rickettsia, including the introduction of molecular methods like sequence comparison (16S rRNA, ompA, ompB, gltA, sca4 …) and the creation of the subspecies status. Genomics and next-generation sequencing have opened a new way to learn more about the pathogenesis and evolution of Rickettsia. The first part of this thesis is a review on the advantages and limitations of genomics in prokaryotic taxonomy, while the second part consists of the genomic analyses of five Rickettsia subspecies and a new Rickettsia species. Using high-throughput sequencing methods, we obtained the draft genomes of R. sibirica sibirica, R. sibirica mongolitimonae, R. conorii indica, R. conorii caspia, R. conorii israelensis, and R. gravesii. This work can be a basis of further studies to increase the understanding on the disease-causing mechanisms, evolutionary relationships, and taxonomy of rickettsiae
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Benevides, Leandro. "Comparative Genomics of Faecalibacterium spp." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS129.
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Dans le côlon humain, le genre Faecalibacterium est le membre principal du groupe Clostridium leptum et comprend le deuxième genre représentatif le plus commun dans les échantillons fécaux, après Clostridium coccoides. Il a été reconnu comme une bactérie importante favorisant la santé intestinale et est aujourd'hui considéré comme un probiotique de prochaine génération. Jusqu'à récemment, on croyait qu'il n'y avait qu'une seule espèce dans ce genre, mais depuis 2012, certaines études ont commencé à suggérer l'existence de deux phylogroupes dans le genre. Cette nouvelle proposition de reclassification dans ce genre augmente l'importance de nouvelles études, toutes souches confondues, pour mieux comprendre la diversité, les interactions avec l'hôte et les aspects sécuritaires dans son utilisation comme probiotique. Brièvement, dans ce travail, nous introduisons les analyses de génomique comparative au genre Faecalibacterium en effectuant une étude phylogénétique profonde et en évaluant les aspects de sécurité pour son utilisation comme probiotique. Les analyses phylogénétiques comprenaient non seulement l'utilisation classique du gène de l'ARNr 16S, mais aussi l'utilisation de 17 génomes et techniques complets comme le typage de séquence multi-locus (wgMLST), l'identité nucléotidique moyenne (ANI), le synténie génique et le pangénome. C'est aussi le premier travail à combiner une analyse du développement du pangénome avec l'analyse ANI afin de corroborer l'attribution de souches à de nouvelles espèces. Les analyses phylogénétiques ont confirmé l'existence de plus d'une espèce dans le genre Faecalibacterium. De plus, l'évaluation de la sécurité impliquait (1) la prédiction des régions acquises horizontalement (îlots de résistance aux antibiotiques, îlots métaboliques et régions phagiques), (2) la prédiction des voies métaboliques, (3) la recherche de gènes liés à la résistance aux antibiotiques et des bactériocines. Ces analyses ont identifié des îlots génomiques dans tous les génomes, mais aucun d'entre eux n'est exclusif à une souche ou à une génospécie. En outre, ont été identifiés 8 gènes liés aux mécanismes de résistance aux antibiotiques répartis entre les génomes. 126 voies métaboliques ont été prédites et parmi certaines ont été mises en évidence: la dégradation du bisphénol A, le métabolisme du butanoate et la biosynthèse de la streptomycine. En outre, nous avons étudié le contexte génomique d'une protéine (molécule anti-inflammatoire microbienne - MAM) décrite pour la première fois par notre groupe. Cette recherche montre que la MAM apparaît proche des gènes liés au processus de sporulation et, dans certaines souches, proche d'un transporteur ABCWithin the human colon, the genus Faecalibacterium is the main member of the Clostridium leptum cluster and comprises the second-most common representative genus in fecal samples, after Clostridium coccoides. It has been recognized as an important bacterium promoting the intestinal health and today is considered as a potential next generation probiotic. Until recently, it was believed that there was only one species in this genus, but since 2012, some studies have begun to suggest the existence of two phylogroups into the genus. This new proposition of reclassification into this genus increases the importance of new studies, with all strains, to better understand the diversity, the interactions with the host and the safety aspects in its use as probiotic. Briefly, in this work we introduce the comparative genomics analyzes to the genus Faecalibacterium performing a deep phylogenetic study and evaluating the safety aspects for its use as a probiotic. The phylogenetic analyzes included not only the classical use of 16S rRNA gene, but also the utilization of 17 complete genomes and techniques like whole genome Multi-Locus Sequence Typing (wgMLST), Average Nucleotide Identity (ANI), gene synteny, and pangenome. Also, this is the first work to combine an analysis of pangenome development with ANI analysis in order to corroborate the assignment of strains to new species. The phylogenetic analyzes confirmed the existence of more than one species into the genus Faecalibacterium. Moreover, the safety assessment involved the (1) prediction of horizontally acquired regions (Antibiotic resistance islands, Metabolic islands and phage regions), (2) prediction of metabolic pathways, (3) search of genes related to antibiotic resistance and (4) search of bacteriocins. These analyzes identified genomic islands in all genomes, but none of than are exclusive to one strain or genospecies. Also, were identified 8 genes related to antibiotic resistance mechanisms distributed among the genomes. 126 metabolic pathways were predicted and among than some were highlighted: Bisphenol A degradation, Butanoate metabolism and Streptomycin biosynthesis. In addition, we studied the genomic context of one protein (Microbial Anti-inflammatory Molecule - MAM) first described by our group. This investigation shows that MAM appears close to genes related to sporulation process and, in some strains, close to an ABC-transporter
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St, Jean Andrew Louis. "Haloarchaeal comparative genomics and the local context model of genomic evolution." Thesis, University of Ottawa (Canada), 1996. http://hdl.handle.net/10393/10308.
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Genomics is a rapidly expanding field of research that seeks to study the structure, function and evolution of an organism's genome. Genomic investigations were conducted on three species of haloarchaea, a monophyletic group of prokaryotes belonging to the kingdom Euryarchaeota of the domain Archaea that are adapted to high-salt environments. A physical and genetic map of the genome of Halobacterium salinarum GRB is described. This map and the previously published map of the genome of Haloferax volcanii DS2 were compared with the object of detecting any conservation in the order or spacing of homologous loci between the two genomes. A computer program--COMPAGEN--was developed to aid in the analysis of the data generated by this comparison. No map order conservation could be detected at the 15 kbp average resolution of this comparison between genomes estimated to have diverged 600 million years ago. A second comparison was performed between the chromosomes of Haloferax volcanii DS2 and Haloferax mediterranei ATCC 33500 (R-4). Extensive conservation was found between these two genomes which diverged approximately 80 million years ago showing only three rearrangements: two inversions and a transposition. Conclusions drawn from an analysis of the comparisons include: (1) that higher resolution is required to deal with distantly related genomes, likely making use of sequence data, and (2) that it is important to compare genomes that have diverged at different times if one wishes to investigate the dynamics of genomic evolution within a phylogenetic group. The local context model was developed in an effort to explain the pattern of conservation and divergence seen in these and other prokaryotic genome comparisons. This model states that since the expression of genes is affected by flanking genetic elements, genes will resist changing their position relative to one another so long as this change is likely to alter gene expression in a way deleterious to the cell. The local context model thus provides a force promoting the conservation of genomic map order. The implications of this model for the evolution of the haloarchaea is discussed and future directions of prokaryotic genomics in general is explored.
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Prakash, Amol. "Algorithms for comparative sequence analysis and comparative proteomics /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/6904.
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Gaiarsa, S. "EVOLUTION, COMPARATIVE GENOMICS AND GENOMIC EPIDEMIOLOGY OF BACTERIA OF PUBLIC HEALTH IMPORTANCE." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/525881.
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La presente tesi è incentrata sull'epidemiologia genomica delle infezioni batteriche ospedaliere. L'ambiente ospedaliero è peculiare, in quanto al suo interno si concentrano un elevato numero di agenti batterici, pazienti con un sistema immunitario debole e un uso massiccio di sostanze antimicrobiche. Questa combinazione favorisce lo sviluppo e la selezione di ceppi resistenti agli antibiotici e la diffusione di infezioni opportunistiche: in generale il prosperare dei patogeni nosocomiali. Alcune tecniche all'avanguardia per lo studio di questo tipo di infezioni sono basate sull’uso della genomica e di approcci evoluzionistici: esse permettono di conoscere le caratteristiche genomiche dei ceppi batterici e di ricostruire la loro storia evolutiva. Grazie alla possibilità di sequenziare il DNA ad un prezzo sempre più economico, i progetti di ricerca sono supportati da un numero sempre crescente di genomi e i dati genomici depositati nelle banche dati sono in crescita esponenziale: questo rende possibile eseguire una varietà sempre maggiore di analisi.
Il primo lavoro qui riportato descrive l'evoluzione del Clonal Complex 258 (CC258) di Klebsiella pneumoniae. Le mutazioni puntiformi (single nucleotide polymorphism, SNP) hanno permesso di ricostruire la filogenesi globale di tutta la specie e di collocare il CC258 nel suo contesto evolutivo. Successivamente, è stato possibile rilevare la presenza di una ricombinazione di 1,3 Mb nei genomi del clade in analisi. Un’analisi del molecular clock ha poi consentito di datare sia questo che gli altri eventi di ricombinazione scoperti in lavori precedenti. Questi risultati sono stati usati per completare il quadro della storia evolutiva del CC258, caratterizzata da frequenti eventi di macro-ricombinazione. Un’evoluzione rapida e caratterizzata da scambi di elevate quantità di informazioni genomiche è una caratteristica comune ad altri patogeni nosocomiali che sviluppano fenotipi da "superbatteri".
Sebbene frequente, il modello di evoluzione per macro-ricombinazioni non è comune a tutti i batteri responsabili di infezioni nosocomiali. Un’eccezione è il ceppo SMAL di Acinetobacter baumannii, presentato in un altro sottoprogetto di questa tesi. In questo lavoro sono stati analizzati i genomi del sequence type (ST) 78 di A. baumannii. La filogenesi e la genomica comparativa hanno rivelato la presenza di due differenti cladi all'interno del ST che presentano differenti "stili" evolutivi. Un gruppo (contenente i genomi SMAL) è caratterizzato da una minore variabilità del contenuto genico e dalla presenza di un numero più elevato di copie di insertion sequence (IS). Una IS interrompe il gene comEC/rec2 in tutti i genomi SMAL. Questo gene codifica per una proteina coinvolta nell’acquisizione del DNA esogeno, quindi la sua inattivazione limita lo scambio di geni. Questo suggerisce una spiegazione per la bassa plasticità genomica.
In un altro lavoro presentato in questa tesi, l'epidemiologia genomica è stata applicata per ricostruire la diffusione di un focolaio epidemico di K. pneumoniae in un’unità di terapia intensiva ospedaliera. In un primo momento, è stato utilizzato un approccio filogenetico per separare gli isolati appartenenti all'epidemia da quelli sporadici. Poi le date di isolamento e gli SNP genomici hanno permesso di costruire una rete genomica che modellasse la propagazione delle infezioni nel reparto. La ricostruzione ha indicato una diffusione radiale del patogeno dal paziente zero a tutti gli altri infetti, rivelando così un errore sistematico nelle procedure di biosicurezza dell'ospedale.
Questa applicazione quasi forense dell'epidemiologia genomica è stata utilizzata anche in altri due lavori qui presentati, entrambi riguardanti la ricostruzione di infezioni alimentari. In uno degli articoli, incentrato su Salmonella enterica, l’analisi filogenetica è stata eseguita solamente con gli SNP sinonimi al fine di filtrare le mutazioni patoadattative. Nell'altro lavoro sono stati utilizzati dati epidemiologici, tipizzazione molecolare e filogenesi basata sugli SNP per studiare l'infezione di nove isolati di Listeria monocytogenes, che si ritenevano essere parte dello stesso focolaio e alla fine sono risultati genomicamente non correlati.
Infine, viene qui presentato anche un articolo di review riguardante l'epidemiologia genomica. L'articolo è focalizzato sulle ultime pubblicazioni ad alto impatto che analizzano l'evoluzione genomica degli agenti patogeni batterici e le dinamiche di propagazione delle epidemie in brevi periodi di tempo. L'articolo descrive, infine, le ultime ricostruzioni epidemiologiche a livello storico, che sono possibili grazie alle moderne tecnologie di isolamento e sequenza del DNA.The present thesis is focused on genomic epidemiology of bacterial hospital infections. The hospital environment is unique, as it concentrates a high number of bacterial agents, frequent antibiotic use, and patients with weak immune systems. This combination favours the development and selection of antibiotic resistant strains and the spread of opportunistic infections: in general the thriving of nosocomial pathogens. Genomics and evolutionary approaches have emerged as the cutting edge tools for studying this kind of infections, allowing to study the genomic features of bacterial strains and their evolution. Thanks to the possibility to sequence DNA at a constantly cheaper price, research projects are supported by a growing number of genomes and a considerable amount of genomic data is available in the databases, expanding the amount of possible investigations that can be performed. The first work presented here describes the evolution of the Clonal Complex 258 (CC258) of Klebsiella pneumoniae. Single nucleotide polymorphisms (SNPs) allowed to reconstruct the global phylogeny of the entire species and to collocate the CC258 in its evolutionary context. Furthermore, it was possible to detect the presence of a 1.3 Mb recombination in the genomes of the clade in analysis. A molecular clock approach allowed to date this and other previously discovered recombination events. These findings were used to complete the picture of the evolutionary history of CC258, which is characterized by frequent macro-recombination events. A quick evolutive strategy characterized by exchange of high amount of information is a common feature to other nosocomial pathogens, which develop “superbug” phenotypes. Although common, the macro-recombination evolution model is not shared by all nosocomial infection bacteria. One exception is the SMAL strain of Acinetobacter baumannii, presented in another subproject of this thesis. In this work, the genomes of Sequence Type (ST) 78 of A. baumannii were analyzed. Phylogeny and comparative genomics revealed the presence of two different clades within the ST, presenting different evolutive “lifestyles”. One group (containing the SMAL genomes) was characterized by a lower gene content variability and by the presence of a higher copy number of insertion sequences (ISs). One IS interrupts the comEC/rec2 gene in all the SMAL genomes. This gene codes for a protein involved in the exogenous DNA importation, thus its inactivation limits the gene exchange, suggesting an explanation for the low genomic plasticity. In another work presented in this document, genomic epidemiology was applied to reconstruct the spreading routes of a K. pneumoniae epidemic event in an hospital intensive care unit. At first, a phylogenetic approach was used to separate the isolates that belonged to the outbreak from the sporadic ones. Then the isolation dates and genomic SNPs allowed to build a genomic network, which modelled the chain of infection events in the ward. The reconstruction suggested a star-like diffusion of the pathogen from patient zero to the other infected ones, thus revealing a systematic error in the biosafety procedures of the hospital. This almost-forensic application of genomic epidemiology was also used in two other works presented, both of them concerning the reconstruction of food-borne infections. In one of the works, focused on Salmonella enterica, only synonymous SNPs were used as input to a phylogenetic based investigation, in order to filter out pathoadaptative mutations. In the other article, epidemiological data, molecular typing and SNP-based phylogeny were used to investigate the infection of nine Listeria monocytogenes isolates, which were believed to be part of the same outbreak and in the end proved to be genomically unrelated. Lastly, a review paper on genomic epidemiology is also presented. The article is focused on the latest high impact publications analyzing the genome evolution of bacterial pathogens as well as the propagation dynamics of epidemic outbreaks in very short periods of time. The article also describes the latest historical epidemiological studies, which are possible thanks to modern DNA isolation and sequencing technologies.
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Dessimoz, Christophe. "Comparative genomics using pairwise evolutionary distances /." Zürich : ETH, 2009. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=18177.
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Ulrich, Luke. "Comparative Genomics of Microbial Signal Transduction." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/7632.
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High-throughput genome processing, sophisticated protein sequence analysis, programming, and information management were used to achieve two major advances in the comparative genomics of microbial signal transduction. First, an integrated and flexible bioinformatics platform and the Microbial Signal Transduction database (MiST) were developed, which facilitated the genome-wide analysis of bacterial signal transduction. This platform was used successfully for the high-throughput identification and classification of signal transduction proteins in more than 300 archaeal and bacterial organisms. Second, analysis of information encoded in prokaryotic genomes revealed that the majority of signal transduction systems consist of one-component systems a single protein containing both input and output domains but lacking phosphotransfer domains typical of two-component systems. The prevalence of one-component systems is a paradigm-shifting discovery because two-component systems are currently viewed as the primary mode of signal transduction in prokaryotes. One-component systems are more widely distributed among bacteria and archaea and display a greater diversity of domains than two-component systems. Additionally, in-depth bioinformatic analyses were performed that further characterized the function of two, input, signaling domains. In summary, this systematic, high-throughput delineation of microbial signal transduction is another step forward in our understanding of the genomic basis of life.
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Golenetskaya, Natalia. "Adressing scaling challenges in comparative genomics." Phd thesis, Université Sciences et Technologies - Bordeaux I, 2013. http://tel.archives-ouvertes.fr/tel-00865840.
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La génomique comparée est essentiellement une forme de fouille de données dans des grandes collections de relations n-aires. La croissance du nombre de génomes sequencés créé un stress sur la génomique comparée qui croit, au pire géométriquement, avec la croissance en données de séquence. Aujourd'hui même des laboratoires de taille modeste obtient, de façon routine, plusieurs génomes à la fois - et comme des grands consortia attend de pouvoir réaliser des analyses tout-contre-tout dans le cadre de ses stratégies multi-génomes. Afin d'adresser les besoins à tous niveaux il est nécessaire de repenser les cadres algorithmiques et les technologies de stockage de données utilisés pour la génomique comparée. Pour répondre à ces défis de mise à l'échelle, dans cette thèse nous développons des méthodes originales basées sur les technologies NoSQL et MapReduce. À partir d'une caractérisation des sorts de données utilisés en génomique comparée et d'une étude des utilisations typiques, nous définissons un formalisme pour le Big Data en génomique, l'implémentons dans la plateforme NoSQL Cassandra, et évaluons sa performance. Ensuite, à partir de deux analyses globales très différentes en génomique comparée, nous définissons deux stratégies pour adapter ces applications au paradigme MapReduce et dérivons de nouveaux algorithmes. Pour le premier, l'identification d'événements de fusion et de fission de gènes au sein d'une phylogénie, nous reformulons le problème sous forme d'un parcours en parallèle borné qui évite la latence d'algorithmes de graphe. Pour le second, le clustering consensus utilisé pour identifier des familles de protéines, nous définissons une procédure d'échantillonnage itérative qui converge rapidement vers le résultat global voulu. Pour chacun de ces deux algorithmes, nous l'implémentons dans la plateforme MapReduce Hadoop, et évaluons leurs performances. Cette performance est compétitive et passe à l'échelle beaucoup mieux que les algorithmes existants, mais exige un effort particulier (et futur) pour inventer les algorithmes spécifiques.
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Buchan, Daniel William Alexander. "Protein domain evolution by comparative genomics." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407753.
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Kamvysselis, Manolis 1977. "Computational comparative genomics : genes, regulation, evolution." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/7999.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references (p. 95-99).
Understanding the biological signals encoded in a genome is a key challenge of computational biology. These signals are encoded in the four-nucleotide alphabet of DNA and are responsible for all molecular processes in the cell. In particular, the genome contains the blueprint of all protein-coding genes and the regulatory motifs used to coordinate the expression of these genes. Comparative genome analysis of related species provides a general approach for identifying these functional elements, by virtue of their stronger conservation across evolutionary time. In this thesis we address key issues in the comparative analysis of multiple species. We present novel computational methods in four areas (1) the automatic comparative annotation of multiple species and the determination of orthologous genes and intergenic regions (2) the validation of computationally predicted protein-coding genes (3) the systematic de-novo identification of regulatory motifs (4) the determination of combinatorial interactions between regulatory motifs. We applied these methods to the comparative analysis of four yeast genomes, including the best-studied eukaryote, Saccharomyces cerevisiae or baker's yeast. Our results show that nearly a tenth of currently annotated yeast genes are not real, and have refined the structure of hundreds of genes. Additionally, we have automatically discovered a dictionary of regulatory motifs without any previous biological knowledge. These include most previously known regulatory motifs, and a number of novel motifs. We have automatically assigned candidate functions to the majority of motifs discovered, and defined biologically meaningful combinatorial interactions between them. Finally, we defined the regions and mechanisms of rapid evolution, with important biological implications.
(cont.) Our results demonstrate the central role of computational tools in modem biology. The analyses presented in this thesis have revealed biological findings that could not have been discovered by traditional genetic methods, regardless of the time or effort spent. The methods presented are general and may present a new paradigm for understanding the genome of any single species. They are currently being applied to a kingdom-wide exploration of fungal genomes, and the comparative analysis of the human genome with that of the mouse and other mammals.
by Manolis (Kellis) Kamvysselis.
Ph.D.
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Coates-Brown, Rosanna. "Comparative genomics of the skin staphylococci." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2046659/.
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The human skin is a complex ecosystem which supports a diverse population of bacteria. Comparative genomic analyses are increasingly being used to explore the functional potential of this bacterial population . The ubiquity of Staphylococcus on human skin means this genus represents the most well-studied of the microbial skin residents, however most analysis has focussed on the significant clinical pathogenic species S. epidermidis and S. aureus. To investigate the biology of S. hominis, the second most frequent Staphylococcus species isolated from human skin after S. epidermidis, seven isolates were sequenced using Illumina and PacBio technologies. An intraspecies comparative genomic analysis was performed with these and several publically available S. hominis genomes to identify core and accessory genes. The complement of encoded cell wall-anchored proteins was studied using bioinformatics to describe the range of surface-attached proteins and revealed a unique species set. Investigation also revealed the presence of S. hominis genes described as virulence factors in S. aureus and S. epidermidis. This further highlights non-pathogenic staphylococci as a reservoir of genes, which can be exchanged with pathogenic S. aureus, and the potential for recruitment of these genes into virulence pathways. Interspecies comparative analysis of twenty Staphylococcus species, based on clusters of orthologous genes, confirmed the designation of staphylococcal species groups previously established by DNA-DNA hybridisation and single gene analysis methods. The bioinformatic algorithm randomForest was used to identify drivers forming species groups based on the orthologous gene cluster analysis leading to a subset of orthologous clusters defined as being contributory. This interspecies analysis also revealed diversity between the staphylococcal species groups with respect to their response mechanisms for antimicrobial peptide (AMP) resistance. Specifically, the presence or absence of the BraRS two-component system (TCS) was identified to be one of the important drivers differentiating a nine species member group that included S. aureus, S. hominis and S. epidermidis. Experimental evolution in the presence of the lantibiotic nisin was used to dissect differences in the global response of the BraRS-positive species S. hominis and S. aureus, from the BraRS-negative species S. saprophyticus, . Identified SNPs from the resistance evolution revealed complex relationships between the regulons of staphylococcal TCSs and identified that YurK should be investigated for a potential role in AMP resistance of S. aureus and S. hominis.
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Moore, Matthew Phillip. "Comparative genomics of Pseudomonas aeruginosa populations." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3021281/.
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Pseudomonas aeruginosa causes a wide range of infections, is often associated with antimicrobial resistance and is the primary cause of chronic lung infection in cystic fibrosis (CF) and the overall morbidity and mortality associated with the disease. As P. aeruginosa is an environmental bacterium that opportunistically infects CF patients most infecting lineages are distinct. The determination of common adaptive routes during infection is further complicated by within-lineage heterogeneity, multi-lineage infections and the emergence of transmissible strains. In order to better understand the genetic basis of varying pathogenicity, a diverse dataset of 1,407 P. aeruginosa genomes from the environment, non-CF bronchiectasis and from CF samples was analysed. Detailed analysis of mutations potentially associated with the CF lung environment was conducted by comparison of the genomes from CF and environmental isolates and by including a geographically and historically diverse panel of a transmissible lineage, the Liverpool Epidemic Strain (LES). Sequencing of isolates from non-CF bronchiectasis showed for the first time the commonality in adaptive routes in non-CF chronic lung diseases and the utility of genome sequencing to infer within and between host diversity and population structure. Many antibiotic resistance genes (ARGs) in all samples were observed to be adaptive and a sample of genomes from hospital isolates from Thailand was used to assess international multi-drug resistance lineages with mobile genetic element associated ARGs. This study has shown, by analysis of diverse datasets, how genome sequencing can reveal the genetic basis of phenotypic heterogeneity and subsequent varying patient outcomes with this diverse infection.
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Mularoni, Loris. "Comparative genomics of amino acid tandem repeats." Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7187.
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Tandem amino acid repeats, also known as homopolimeric tract or homopeptides, are very common features of eukaryotic genomes and are present in nearly one-fifth of human encoded proteins. These structures have attracted much interest in the early 1990s when a number of neurological diseases associated with repeat expansion mutations were discovered in humans. Despite their abundance in coding proteins, little is known about their functional consequences. Two scenarios have been proposed. In one, tandem amino acid repeat is considered a neutral structure generated by slippage event and eventually tolerated in protein as long as it does not disrupt the protein function. However, an increasing number of studies proposed that tandem amino acid repeats may be involved in important functional or structural roles. For instance, tandem amino acid repeats had been found to be especially abundant in transcription factors and developmental proteins, where they can potentially modulate protein-protein interaction, exert an effect on gene transcriptional activity, or act as spacer between different protein domains. In addition, several studies have linked changes in repeat size to modification in developmental processes. Despite the advancement made in the last decade, little is known about the selective forces that shape their evolution. The aim of this thesis has been to gain further insight onto the evolutionary dynamics of tandem amino acid repeats by studying the different types of mutations that occur in the amino acid component of the human proteome, by studying the relationship between variability and abundance of amino acid tandem with the evolutionary constraints operating on the proteins, and by studying their conservation and distribution across various vertebrate genomes in both coding and non-coding sequences. The integration of these approaches enabled us to outline an evolutionary model of these structures.
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Wuichet, Kristin. "Comparative Genomics of the Microbial Chemotaxis System." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/16193.
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This research project presents a comprehensive functional analysis of a complex prokaryotic signal transduction system and the mechanisms underlying its evolution. The chemotaxis system regulates motility in prokaryotes and is their most complex signal transduction system. The system has been extensively characterized experimentally, but recent studies have created new questions about the function and origin of this system. Comparative genomics analyses are well-suited for studying the chemotaxis system since it is present in taxonomically diverse organisms. The first aim of this project is to understand the evolutionary history of the chemotaxis system that has resulted in the diversity of chemotaxis systems that have been experimentally. The results reveal three functional families of chemotaxis systems that regulate flagellar motility, type IV pili motility, and non-motility outputs. The flagellar family shows extensive diversity with 10 conserved classes that have variable accessory proteins, and these classes show a co-evolutionary relationship with flagella. The second aim of this project is to analyze the molecular evolution of chemotaxis system components and utilize that information to predict the contact sites involved in protein-protein interactions. The analysis supports that there is evolutionary pressure at the amino acid sequence level to maintain protein-protein interactions. From this observation, a method to predict the contact sites of protein-protein interactions from sequence information alone was developed and validated by experimental and structural information.
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Fuxelius, Hans-Henrik. "Methods and Applications in Comparative Bacterial Genomics." Doctoral thesis, Uppsala universitet, Molekylär evolution, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8398.
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Comparative studies of bacterial genomes, now counting in the hundreds, generate massive amounts of information. In order to support a systematic and efficient approach to genomic analyses, a database driven system with graphic visualization of genomic properties was developed - GenComp. The software was applied to studies of obligate intracellular bacteria. In all studies, ORFs were extracted and grouped into ORF-families. Based on gene order synteny, orthologous clusters of core genes and variable spacer ORFs were identified and extracted for alignments and computation of substitution frequencies. The software was applied to the genomes of six Chlamydia trachomatis strains to identify the most rapidly evolving genes. Five genes were chosen for genotyping, and close to a 3-fold higher discrimination capacity was achieved than that of serotypes. With GenComp as the backbone, a massive comparative analysis were performed on the variable gene set in the Rickettsiaceae, which includes Rickettsia prowazekii and Orientia tsutsugamushi, the agents of epidemic and scrub typhus, respectively. O. tsutsugamushi has the most exceptional bacterial genome identified to date; the 2.2 Mb genome is 200-fold more repeated than the 1.1 Mb R. prowazekii genome due to an extensive proliferation of conjugative type IV secretion systems and associated genes. GenComp identified 688 core genes that are conserved across 7 closely related Rickettsia genomes along with a set of 469 variably present genes with homologs in other species. The analysis indicates that up to 70% of the extensively degraded and variably present genes represent mobile genetic elements and genes putatively acquired by horizontal gene transfer. This explains the paradox of the high pseudogene load in the small Rickettsia genomes. This study demonstrates that GenComp provides an efficient system for pseudogene identification and may help distinguish genes from spurious ORFs in the many pan-genome sequencing projects going on worldwide.
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Garikipati, Dilip Kumar. "The comparative genomics and physiology of myostatin." Online access for everyone, 2007. http://www.dissertations.wsu.edu/Dissertations/Summer2007/D_Garikipati_070807.pdf.
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Mostowy, Serge. "Comparative genomics of the Mycobacterium tuberculosis complex." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111834.
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The study of microbial evolution has been recently accelerated by the advent of comparative genomics, an approach enabling investigation of organisms at the whole-genome level. Tools of comparative genomics, including the DNA microarray, have been applied in bacterial genomes towards studying heterogeneity in DNA content, and to monitor global gene expression. When focused upon the study of microbial pathogens, genome analysis has provided unprecedented insight into their evolution, virulence, and host adaptation. Contributing towards this, I herein explore the evolutionary change affecting genomes of the Mycobacterium tuberculosis complex (MTC), a group of closely related bacterial organisms responsible for causing tuberculosis (TB) across a diverse range of mammals. Despite the introduction nearly a century ago of BCG, a family of live attenuated vaccines intentioned on preventing human TB, the uncertainty surrounding its usefulness is punctuated by the reality that TB continues to be responsible for claiming over 2 million lives per year. As pursued throughout this thesis, a precise understanding of the differences in genomic content among the MTC, and its impact on gene expression and biological function, promises to expose underlying mechanisms of TB pathogenesis, and suggest rational approaches towards the design of improved diagnostics and vaccines to prevent disease.With the availability of whole-genome sequence data and tools of comparative genomics, our publications have advanced the recognition that large sequence polymorphisms (LSPs) deleted from Mycobacterium tuberculosis, the causative agent of TB in humans, serve as accurate markers for molecular epidemiologic assessment and phylogenetic analysis. These LSPs have proven informative both for the types of genes that vary between strains, and for the molecular signatures that characterize different MTC members. Genomic analysis of atypical MTC has revealed their diversity and adaptability, illuminating previously unexpected directions of MTC evolution. As demonstrated from parallel analysis of BCG vaccines, a phylogenetic stratification of genotypes offers a predictive framework upon which to base future genetic and phenotypic studies of the MTC. Overall, the work presented in this thesis has provided unique insights and lessons having direct clinical relevance towards understanding TB pathogenesis and BCG vaccination.
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Li, Yang. "Understanding lineage-specific biology through comparative genomics." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:23398cc7-8bbe-4f5a-8cd9-1104591400cc.
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A major challenge in biology is to identify how different species arose and acquired distinct phenotypic traits. High-throughput sequencing is transforming our understanding of biology by allowing us to study genomes and cellular processes at genome-wide levels. Only a decade subsequent to the publication of the first human genome draft, genome assemblies of hundreds of organisms have been produced. Yet, genome analysis remains challenging and advances have lagged far behind our sequencing abilities and other technological advances. The next generation of comparative genomicists must therefore understand, invent and apply a wide number of computational tools in order to study biology in the most efficient manner and in order to pose the most interesting questions. This thesis spans areas covering evolutionary genomics, gene regulation, and computational methods development. A major aim was to understand how genetic variation contributes to variation in phenotypic traits. This was approached using a large variety of evolutionary and comparative genomics tools. In particular, high-throughput sequencing datasets were analysed to study single-cell transcriptomics, gene duplications, gene architecture evolution, and alternative splicing. Additionally, in cases where off-the-shelf analysis tools were inexistent, novel pipelines and programs were designed and implemented to solve algorithmic problems such as scaffolding genome assemblies and short-read mapping onto small exons.
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Park, Gyoungju Nah. "Comparative Genomics in Two Dicot Model Systems." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/194279.
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Comparative sequence analyses were performed with members of the Solanaceae and the Brassicaceae. These studies investigated genomic organization, determined levels of microcolinearity, identified orthologous genes and investigated the molecular basis of trait differences. The first analysis was performed by comparison of tomato (Solanum lycopersicum) genomic sequence (119 kb) containing the JOINTLESS1 (J1) locus with orthologous sequences from two potato species, a diploid, Solanum bulbocastanum (800-900 Mb, 2N=2X=24), and a hexaploid, Solanum demissum (2,700 Mb, 2N=6X=72). Gene colinearity was well maintained across all three regions. Twelve orthologous open reading frames were identified in identical order and orientation and included three putative J1 orthologs with 93-96% amino acid sequence identity in both potato species. Although these regions were highly conserved, several local disruptions were detected and included small-scale expansion/contraction regions with intergenic sequences, non-colinear genes and transposable elements. Three putative Solanaceous-specific genes were also identified in this analysis. The second analysis was performed by comparison of a Thellungiella halophila (T. halophila) genomic sequence (193 kb) containing the SALT OVERLY SENSITIVE1 (SOS1) locus with the orthologous sequence (146 kb) in Arabidopsis thaliana (Arabidopsis). T. halophila is a halophytic relative of Arabidopsis thaliana that exhibits extreme salt tolerance. Twenty-five genes, including the putative T. halophila SOS1 (ThSOS1), showed a high degree of colinearity with Arabidopsis genes in the corresponding region. Although the two sequences were significantly colinear, several local rearrangements were detected which were caused by tandem duplications and inversions. Three major expansion/contraction regions in T. halophila contained five LTR retrotransposons which contributed to genomic size variation in this region. ThSOS1 shares similar gene structure and sequence with Arabidopsis SOS1 (AtSOS1), including 11 transmembrane domains and a cyclic nucleotide-binding domain. Three Simple Sequence Repeats (SSRs) were detected within a 540 bp region upstream of the putative translational start site in ThSOS1. The (CTT)n repeat is present in different copy numbers in ThSOS1 (18 repeats) and AtSOS1 (3 repeats). When present in the 5' UTRs of some Arabidopsis genes, (CTT)n serves as a putative salicylic acid responsive element. These SSRs may serve as cis-acting elements affecting differential mRNA accumulation of SOS1 in the two species.
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Syme, Robert Andrew. "Comparative Genomics of Parastagonospora and Pyrenophora species." Thesis, Curtin University, 2015. http://hdl.handle.net/20.500.11937/54044.
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The advancing technology and tools available for the important agricultural pathogens P. nodorum and P. avenaria pathosystems are leveraged here for intra-species comparison as well as comparisons to other related species. The comparisons have yielded insight into the evolutionary history of pathogen and host, insights into the mechanisms of genome evolution, and prediction of genes integral to fungal pathogenicity.
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Dang, Ha Xuan. "Mold Allergomics: Comparative and Machine Learning Approaches." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/64205.
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Fungi are one of the major organisms that cause allergic disease in human. A number of proteins from fungi have been found to be allergenic or possess immunostimulatory properties. Identifying and characterizing allergens from fungal genomes will help facilitate our understanding of the mechanism underlying host-pathogen interactions in allergic diseases. Currently, there is a lack of tools that allow us to rapidly and accurately predict allergens from whole genomes. In the context of whole genome annotation, allergens are rare compared to non-allergens and thus the data is considered highly skewed. In order to achieve a confident set of predicted allergens from a genome, false positive rates must be lowered. Current allergen prediction tools often produce many false positives when applied to large-scale data set such as whole genomes, and thus lower the precision. Moreover, the most accurate tools are relatively slow because they use sequence alignment to construct feature vectors for allergen classifiers. This dissertation presents computational approaches in characterizing the allergen repertoire in fungal genomes as part of the whole genome studies of Alternaria, an important allergenic/opportunistic human pathogenic fungus and necrotrophic plant parasite. In these studies, the genomes of multiple Alternaria species were characterized for the first time. Functional elements (e.g. genes, proteins) were first identified and annotated from these genomes using computational tools. Protein annotation and comparative genomics approaches revealed the link between Alternaria genotypes and its prolific saprophytic lifestyle that provides at least a partial explanation for the development of pathological relationships between Alternaria and humans. A machine learning based tool (Allerdictor) was developed to address the neglected problem of allergen prediction in highly skewed large-scale data sets. Allerdictor exhibited high precision over high recall at fast speed and thus it is a more practical tool for large-scale allergen annotation compared with existing tools. Allerdictor was then used together with a comparative genomics approach to survey the allergen repertoire of known allergenic fungi. We predicted a number of mold allergens that have not been experimentally characterized. These predicted allergens are potential candidates for further experimental and clinical validation. Our approaches will not only facilitate the study of allergens in the increasing number of sequenced fungal genomes but also will be useful for allergen annotation in other species and rapid prescreening of synthesized sequences for potential allergens.Ph. D.
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Seibert, Sara Rose. "Host-parasite interactions: comparative analyses of population genomics, disease-associated genomic regions, and host use." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1590585260282244.
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Kang, Lin. "Comparative Genomics Insights into Speciation and Evolution of Hawaiian Drosophila." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/85467.
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Speciation and adaptation have always been of great interest to biologists. The Hawaiian archipelago provides a natural arena for understanding adaptive radiation and speciation, and genomics and bioinformatics offer new approaches for studying these fundamental processes. The mode of speciation should have profound impacts on the genomic architecture and patterns of reproductive isolation of new species. The Hawaiian Drosophila are a spectacular example of sequential colonization, adaptive radiation, and speciation in the islands with nearly 1,000 estimated species, of which more than 500 have been described to date.
This dissertation gives an overview of the Hawaiian Drosophila system (Chapter 1), new insights into genomes of three recently diverged species of Hawaiian picture-winged Drosophila (Chapter 2), as well as estimated gene flow patterns (Chapter 3). Additionally, I present a new approach of mapping genomic scaffolds onto chromosomes, based on NextGen sequencing from chromosomal microdissections (Chapter 4), and gene expression profiles of backcross hybrids and their parental forms (Chapter 5). Overall, obtained results were used to address such fundamental questions as the role of adaptive changes, founder effects (small effective population size in isolation), and genetic admixture during speciation.Ph. D.
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Epamino, George Willian Condomitti. "Alinhamento múltiplo de genomas de eucariotos com montagens altamente fragmentadas." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/95/95131/tde-31102017-102826/.
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O advento do sequenciamento de nova geração (NGS - Next Generation Sequencing) nos últimos anos proporcionou um aumento expressivo no número de projetos genômicos. De maneira simplificada, as máquinas sequenciadoras geram como resultado fragmentos de DNA que são utilizados por programas montadores de genoma. Esses programas tentam juntar os fragmentos de DNA de modo a obter a representação completa da sequência genômica (por exemplo um cromossomo) da espécie sendo sequenciada. Em alguns casos o processo de montagem pode ser executado com maior facilidade para organismos com genomas de tamanhos pequenos (por exemplo bactérias com genoma em torno de 5Mpb), através de pipelines que automatizam a maior parte da tarefa. Um cenário mais complicado surge quando a espécie possui genoma com grande comprimento (acima de 1Gpb) e elementos repetidos, como no caso de alguns eucariotos. Nesses casos o resultado da montagem é geralmente composto por milhares de fragmentos (chamados de contigs), uma ordem de magnitude muito superior ao número de cromossomos estimado para um organismo (comumente da ordem de dois dígitos), dando origem a uma montagem altamente fragmentada. Uma atividade comum nesses projetos é a comparação da montagem com a de outro genoma como forma de validação e também para identificação de regiões conservadas entre os organismos. Embora o problema de alinhamento par-a-par de genomas grandes seja bem contornado por abordagens existentes, o alinhamento múltiplo (AM) de genomas grandes em estado fragmentado ainda é uma tarefa de difícil resolução, por demandar alto custo computacional e grande quantidade de tempo. Este trabalho consiste em uma metologia para fazer alinhamento múltiplo de genomas grandes de eucariotos com montagens altamente fragmentadas. Nossa implementação, baseada em alinhamento estrela, se mostrou capaz de fazer AM de grupos de montagens com diversos níveis de fragmentação. O maior deles, um conjunto de 5 genomas de répteis, levou 14 horas de processamento para fornecer um mapa de regiões conservadas entre as espécies. O algoritmo foi implementado em um software que batizamos de FROG (FRagment Overlap multiple Genome alignment), de código aberto e disponível sob licença GPLv3.The advent of Next Generation Sequencing (NGS) in recent years has led to an expressive increase in the number of genomic projects. In a simplified way, sequencing machines generate DNA fragments that are used by genome assembler software. These programs try to merge the DNA fragments to obtain the complete representation of the genomic sequence (for example a chromosome) of the species being sequenced. In some cases the assembling process can be performed more easily for organisms with small-sized genomes (e.g. bacteria with a genome length of approximately 5Mpb) through pipelines that automate most of the task. A trickier scenario arises when the species has a very large genome (above 1Gbp) and complex elements, as in the case of some eukaryotes. In those cases the result of the assembly is usually composed of thousands of fragments (called contigs), an order of magnitude much higher than the number of chromosomes estimated for an organism (usually in the order two digits), giving rise to a highly fragmented assembly. A common activity in these projects is the comparison of the assembly with that of another genome as a form of validation and also to identify common elements between organisms. Although the problem of pairwise alignment of large genomes is well circumvented by existing approaches, multiple alignment of large genomes with highly fragmented assemblies remains a difficult task due to its time and computational requirements. This work consists of a methodology for doing multiple alignment of large eukaryotic genomes with highly fragmented assemblies, a problem that few solutions are able to cope with. Our star alignment-based implementation, was able to accomplish a MSA of groups of assemblies with different levels of fragmentation. The largest of them, a set of 5 reptilian genomes where the B. jararaca assembly (800,000 contigs, N50 of 3.1Kbp) was used as anchor, took 14 hours of execution time to provide a map of conserved regions among the participating species. The algorithm was implemented in a software named FROG (FRagment Overlap multiple Genome alignment), available under the General Public License v3 (GPLv3) terms.
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Steward, Karen Frances. "Comparative genomics of Streptococcus equi and Streptococcus zooepidemicus." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708551.
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Migeon, Pierre. "Comparative genomics of repetitive elements between maize inbred lines B73 and Mo17." Thesis, Kansas State University, 2017. http://hdl.handle.net/2097/35377.
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Master of ScienceGenetics Interdepartmental Program
Sanzhen Liu
The major component of complex genomes is repetitive elements, which remain recalcitrant to characterization. Using maize as a model system, we analyzed whole genome shotgun (WGS) sequences for the two maize inbred lines B73 and Mo17 using k-mer analysis to quantify the differences between the two genomes. Significant differences were identified in highly repetitive sequences, including centromere, 45S ribosomal DNA (rDNA), knob, and telomere repeats. Genotype specific 45S rDNA sequences were discovered. The B73 and Mo17 polymorphic k-mers were used to examine allele-specific expression of 45S rDNA in the hybrids. Although Mo17 contains higher copy number than B73, equivalent levels of overall 45S rDNA expression indicates that transcriptional or post-transcriptional regulation mechanisms operate for the 45S rDNA in the hybrids. Using WGS sequences of B73xMo17 doubled haploids, genomic locations showing differential repetitive contents were genetically mapped, revealing differences in organization of highly repetitive sequences between the two genomes. In an analysis of WGS sequences of HapMap2 lines, including maize wild progenitor, landraces, and improved lines, decreases and increases in abundance of additional sets of k-mers associated with centromere, 45S rDNA, knob, and retrotransposons were found among groups, revealing global evolutionary trends of genomic repeats during maize domestication and improvement.
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Åkerborg, Örjan. "Taking advantage of phylogenetic trees in comparative genomics." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4757.
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Phylogenomics can be regarded as evolution and genomics in co-operation. Various kinds of evolutionary studies, gene family analysis among them, demand access to genome-scale datasets. But it is also clear that many genomics studies, such as assignment of gene function, are much improved by evolutionary analysis. The work leading to this thesis is a contribution to the phylogenomics field. We have used phylogenetic relationships between species in genome-scale searches for two intriguing genomic features, namely and A-to-I RNA editing. In the first case we used pairwise species comparisons, specifically human-mouse and human-chimpanzee, to infer existence of functional mammalian pseudogenes. In the second case we profited upon later years' rapid growth of the number of sequenced genomes, and used 17-species multiple sequence alignments. In both these studies we have used non-genomic data, gene expression data and synteny relations among these, to verify predictions. In the A-to-I editing project we used 454 sequencing for experimental verification. We have further contributed a maximum a posteriori (MAP) method for fast and accurate dating analysis of speciations and other evolutionary events. This work follows recent years' trend of leaving the strict molecular clock when performing phylogenetic inference. We discretised the time interval from the leaves to the root in the tree, and used a dynamic programming (DP) algorithm to optimally factorise branch lengths into substitution rates and divergence times. We analysed two biological datasets and compared our results with recent MCMC-based methodologies. The dating point estimates that our method delivers were found to be of high quality while the gain in speed was dramatic. Finally we applied the DP strategy in a new setting. This time we used a grid laid out on a species tree instead of on an interval. The discretisation gives together with speciation times a common timeframe for a gene tree and the corresponding species tree. This is the key to integration of the sequence evolution process and the gene evolution process. Out of several potential application areas we chose gene tree reconstruction. We performed genome-wide analysis of yeast gene families and found that our methodology performs very well.QC 20100923
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Åkerborg, Örjan. "Taking advantage of phylogenetic trees in comparative genomics /." Stockholm : School of Computer Science and Communication, Kungliga tekniska högskolan, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4757.
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Abbas, Ali Hadi. "Comparative structural genomics and phylogenomics of African trypanosomes." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3022845/.
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The pathogens responsible of the majority of African Animal trypanosomiasis (AAT) are Trypanosoma brucei, T. congolense and T. vivax. These three trypanosomes have very different biology both in the mammalian host and the insect vector. These differences are encoded in their genomes and whole genome sequence comparison of high quality genomic data should allow such comparisons to be performed. Whilst the T.b. brucei strain TREU927 genome assembly is currently aviable as a good quality draft, the current versions of T. congolense and T. vivax are highly fragmented and include large gaps that interrupt genes and physical integrity of genome assembly. Therefore, there is a need to produce high quality de novo genome assemblies of both T. congolense strain IL3000 and T. vivax IL1392. The most appropriate technology for this currently are the third generation sequencing such as PacBio SMRT long reads sequencing. This technology's long reads permit assembly to a high standard with good contig lengths, and more completed gene models. Comparative genomic analysis carried out on T. brucei large chromosomes and the new PacBio de novo assemblies in this thesis T. congolense and T. vivax uncovered putative large structural chromosomal rearrangements between the African trypanosomes. The most extensive examples were noticed between T. vivax and T. brucei, which might reflect the early divergence of former to the most recent divergence of the latter in the phylogenetic tree of African trypanosomes. Remarkably, analysis of T. congolense genome assembly facilitated the full description of (minichromosomes) devoted to harbouring genes utilized mainly in mammalian host immune evasion mechanism. Subsequently, a new gene family consisting of about 30 genes/pseudogenes encode for putative surface proteins (ESAG3- like proteins) was assigned to this trypanosome most likely only found on these chromosomes. The phylogenomic analysis of free living and parasitic kinetoplastids uncovered possible core kinetoplastids, parasitic and African trypanosome specific gene sets. Likewise, the genomic repertoire of some stage specific proteins like Haptoglobin-Hemoglobin receptor, PAG, BARP, ESAG6/7- transferrin like proteins were also present among analysed African trypanosomes. In conclusion, this project has provided genomes that give access to new genomic regions especially, the minichromosomes in two strains T. congolense and other interesting sequences of repeated nature in MBCs like centromeres, moreover, it shows unprecedented chromosomal rearrangements across the three African trypanosomes. Finally, phylogenomic analysis revealed for the first time the genomic repertoire of Haptoglobin- Hemoglobin receptor in the African trypanosomes.
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Xia, Ai. "Comparative genomics of chromosomal rearrangements in malaria mosquitoes." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/37335.
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To better understand the evolutionary dynamics of chromosomal inversions, a physical map for an Asian malaria vector, Anopheles stephensi, was created and compared with the maps of the major African malaria vectors A. gambiae and A. funestus No interchromosomal transposition was observed between A. gambiae and A. stephensi. Several cases of euchromatin and heterochromatin transitions weridentified between A. gambiae and A. stephensi. The study of paracentric inversions between lineages in Anopheles mosquitoes demonstrated that X chromosome has the fastest rate of inversion fixations and highest density of repetitive elements. Among the autosomes, 2R evolved faster than other autosomes. The slowly evolved autosomes have more M/SARs than rapidly evolving arms. Breakpoint regions are enriched with repetitive elements. The study revealed that fixed inversions are distributed nonrandomly and breakpoint clustering is common in lineages of A. gambiae and A. stephensi. The parallel association between the density of inversion fixations and polymorphisms suggests that polymorphic inversions can be fixed during evolution.
To understand the direction of evolution in A. gambiae complex, the ancestral status of fixed inversions for this complex was identified. The presence of the 2La inversion in outgroups, A. stephensi and A. nili, confirmed the ancestral status of the 2La inversion. The presences of breakpoint structure of the 2Ro inversion in outgroup species, A. stephensi, indicated that the 2Ro is ancestral arrangement. The presence of SINE elements at the breakpoints of the 2R+p in A. gambiae PEST strain suggested that the 2R+p is a derived arrangement. Therefore, the carrier of 2Rop inversions, A. merus, was considered closest to the ancestral species.
We have developed a new protocol for laser microdissection and whole genome amplification of polytene chromosomal fragments to obtain DNA for sequencing and assembly. The chromosomal regions spanning both breakpoints of the 2La in A. arabiensis and A. merus were laser microdissected from the polytene chromosomes. Subsequently, DNA samples were amplified using Illustra GenomePhi V2 DNA and Whole-pool amplification methods for obtaining amplicons. Successful amplification of our target DNA was confirmed by PCR with specific primers followed by Sanger sequencing.Ph. D.
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Lyman, Cole Andrew. "Comparative Genomics Using the Colored de Bruijn Graph." BYU ScholarsArchive, 2020. https://scholarsarchive.byu.edu/etd/8441.
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Comparing genomes in a computationally efficient manner is a difficult problem. Methods that provide the highest resolution are too inefficient and methods that are efficient are too low resolution. In this thesis, we show that the Colored de Bruijn Graph (CdBG) is a suitable method for comparing genomes because it is efficient while maintaining a useful amount of resolution. To illustrate the usefulness of the CdBG, the phylogenetic tree for 12 species in the Drosophila genus is reconstructed using pseudo-homologous regions of the genome contained in the CdBG.
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Pryszcz, Leszek Piotr 1985. "Comparative genomics to unravel virulence mechanisms in fungal human pathogens." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/301437.
Full textAbstract:
Las Candidas forman uno de los grupos con mayor n´umero de hongos
pat´ogenos en humanos. La relaci ´on que tienen desde un punto de vista
filogen´etico demuestra que la capacidad de infectar humanos ha surgido
varias veces de forma independiente en este clado. El complejo de Candida
parapsilosis es ideal para investigar la aparici´on de virulencia puesto que
contiene tres especies cercanas que muestran diferentes grados de virulencia
y de importancia: C. parapsilosis, C. orthopsilosis y C. metapsilosis.
En esta tesis presento la secuenciaci´on y posterior an´alisis de quince cepas
de origen cl´ınico y medioambiental que forman parte de este clado. Cabe
remarcar que los genomas de C. orthopsilosis tipo 1 y de C. metapsilosis no se
hab´ıan secuenciado previamente. Nuestros resultados muestran evidencia
gen´omica de la existencia de recombinaci´on, apareamiento e hibridaci´on en
este clado, que previamente se habia considerado asexual. Proponemos que
las cepas cl´ınicas emergieron de forma independiente en linajes de cepas
encontradas en el medioambiente y una posible relaci ´on entre la hibridaci´on
y la adquisici´on de caracter´ısticas relevantes para la virulencia. Finalmente,
para estudiar la aparici´on de virulencia en este clado, hemos comparado,
por primera vez, los genomas de las tres especies que se encuentran dentro
del complejo de Candida parapsilosis. Hemos encontrado expansiones de
familias g´enicas previamente implicadas en virulencia, como es el caso de las
adhesinas, transportadores de membrana y enzimas extracelulares. Tambi´en
hemos observado expansiones de familias de genes que hasta el momento
no han estado relacionadas con virulencia. En resumen, nuestros resultados
aportan una base para poder elaborar numerosas hip´ otesis sobre la aparici´on
de virulencia en las especies de Candida y para que estas hip´ otesis puedan
ser comprobadas posteriormente en el laboratorio.Candida species constitute one of the most prevalent groups of fungal pathogens. From their phylogenetic relationships it is clear that virulence to humans has emerged in this clade several, independent times. The Candida parapsilosis complex is particularly suitable to investigate the emergence of virulence, with three closely-related species of varying degree of pathogenicity and of growing relevance: C. parapsilosis, C. orthopsilosis and C. metapsilosis. In this thesis I present the genome sequencing and analysis of fifteen strains from this clade, sampled from clinical and environmental sources. Notably, genomes of C. orthopsilosis Type 1 and C. metapsilosis were sequenced for the first time. Our results show for the first time the genomic evidence for the existence of recombination, mating and hybridization in this clade, previously considered asexual. We propose the independent emergence of clinical isolates from environmental lineages and a possible role of hybridization in the acquisition of relevant traits for pathogenesis. Finally, in order to gain insight into the emergence of virulence in this clade, we have compared the genomes of all three species of C. parapsilosis complex. We have found expansions in gene families known to be involved in virulence, like adhesins, membrane transporters and extracellular enzymes, as well as expansions in gene families not implicated in virulence so far. Altogether, our findings provide the grounds for numerous hypotheses about the emergence of virulence in Candida spp. and for their future experimental testing. 1
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Perrin, Amandine. "Tools for massive bacterial comparative genomics : Development and Applications." Electronic Thesis or Diss., Sorbonne université, 2022. https://theses.hal.science/tel-03789655.
Full textAbstract:
La génomique comparative bactérienne consiste à comparer les contenus en gène des différentes souches : leur pangenome. Avec le nombre croissant de séquençages, les logiciels existants au début de cette thèse arrivaient à leurs limites en termes de temps de calcul et de mémoire. L’enjeu était de passer à l’échelle de milliers de génomes dans un temps raisonnable, en gardant une précision correcte. De plus, à notre connaissance, aucun logiciel ne permettait d’effectuer toutes les étapes clés d’une étude de génomique comparative. C’est dans ce contexte que nous avons développé PanACoTA, un outil ayant pour but de standardiser et automatiser la préparation de données pour ces études, depuis le téléchargement des génomes et leur contrôle qualité jusqu’à l’inférence de l’arbre phylogénétique du core génome (gènes communs à tous les génomes). Son implémentation sous forme de modules a été pensée pour permettre de s’adapter aux besoins spécifiques de certaines études (exploration de paramètres, étapes supplémentaires). Concernant le module « pangenome », nous avons développé une nouvelle méthode, s’appuyant sur des outils récents de comparaison et clustering de séquences. Robuste aux changements d’échelle, elle permet de calculer un pangénome de 4000 souches en 30 minutes. Au cours de son développement, nous avons appliqué PanACoTA dans différents contextes. Nous avons montré l’utilité de l’outil sur des études à court terme (recherche de la particularité d’une souche épidémique d’E. anophelis), sur du long terme (étude de la diversité génomique de l’espèce E. coli), ou encore pour différencier différentes espèces d’un genre peu connu (Morganella)Bacterial comparative genomics consists in comparing the gene contents of different strains: their pangenome. With the increasing number of strains sequenced, the tools available when I started this PhD were reaching their limits in terms of computation time and space. The aim was to develop a method able to handle thousands of genomes, accurately and in a reasonable amount of time. Besides, to our knowledge, no tool was able to do all key steps of any comparative genomics study. This spurred the development of PanACoTA, a tool to standardize and automatize the process to build the key collections of data needed for these studies. This includes all steps from downloading genomes with a quality control until the inference of a phylogenetic tree based on the core genome (genes shared by all strains). In order to be able to adapt to specific needs (exploration of parameters, additional steps), we implemented it in a modular way. For the “pangenome” module, we developed a new method, based on recent tools of genome comparison and clustering. Robust to changes in sampling size, this method can infer a pangenome of 4000 strains in 30 minutes. During its development, we applied PanACoTA to different kinds of studies. We showed its usefulness for short-term studies (find specificity of a pathogenic strain of E. anophelis), long-term (genomic diversity of E. coli species), or to identify different species in an little-known genus (Morganella)
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Bate, Rachael. "Mapping and gene identification within the Ids to Dmd region of the mouse X chromosome." Thesis, Oxford Brookes University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247810.
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Karanam, Suresh Kumar. "Automation of comparative genomic promoter analysis of DNA microarray datasets." Thesis, Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04062004-164658/unrestricted/karanam%5Fsuresh%5Fk%5F200312%5Fms.pdf.
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Cheung, Hiu Tung (Tom). "Understanding mammalian transcriptional regulation using comparative and functional genomics." Diss., Connect to online resource, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3207751.
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Saski, Christopher A. "Chloroplast comparative genomics implications for phylogeny, evolution and biotechnology /." Connect to this title online, 2007. http://etd.lib.clemson.edu/documents/1193080368/.
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Wagner, Darlene Darlington. "Comparative genomics reveal ecophysiological adaptations of organohalide-respiring bacteria." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/45916.
Full textAbstract:
Organohalide-respiring Bacteria (OHRB) play key roles in the reductive
dehalogenation of natural organohalides and anthropogenic chlorinated contaminants. Reductive dehalogenases (RDases) catalyze the cleavage of
carbon-halogen bonds, enabling respiratory energy conservation and growth. Large numbers of RDase genes, a majority lacking experimental characterization
of function, are found on the genomes of OHRB. In silico genomics tools were employed to identify shared sequence features among RDase genes and proteins,
predict RDase functionality, and elucidate RDase evolutionary history. These analyses showed that the RDase superfamily could be divided into proteins
exported to the membrane and cytoplasmic proteins, indicating that not all RDases function in respiration. Further, Hidden Markov models (HMMs) and
multiple sequence alignments (MSAs) based upon biochemically characterized RDases identified previously uncharacterized members of an RDase superfamily,
delineated protein domains and amino acid motifs serving to distinguish RDases from unrelated iron-sulfur proteins. Such conserved and discriminatory features among RDases may facilitate monitoring of organohalide-degrading microbial
communities or improve accuracy of genome annotation. Phylogenetic analyses of RDase superfamily sequences provided evidence of convergent evolution and horizontal gene transfer (HGT) across distinct OHRB
genera. Yet, the low frequency of RDase transfer outside the genus level and the absence of RDase transfer between phyla indicate that RDases evolve primarily
by vertical evolution or HGT is restricted among related OHRB strains. Polyphyletic evolutionary lineages within the RDase superfamily comprise
distantly-related RDases, some exhibiting activities towards the same substrates, suggesting a longstanding history of OHRB adaptation to natural organohalides. Similar functional and phylogenetic analyses provided evidence that nitrous oxide (N₂O, a potent greenhouse gas) reductase (nosZ) genes from versatile OHRB members of the Anaeromyxobacter and Desulfomonile genera comprised a nosZ sub-family evolutionarily distinct from nosZ found in non-OHRB denitrifiers. Hence, elucidation of RDase and NosZ sequence diversity may enhance the mitigation of anthropogenic organohalides and greenhouse gases (i.e., N₂O), respectively. The tetrachloroethene-respiring bacterium Geobacter lovleyi strain SZ exhibited genomic features distinguishing it from non-organohalide-respiring
members of the Geobacter genus, including a conjugative pilus transfer gene cluster, a chromosomal genomic island harboring two RDase genes, and a
diminished set of c-type cytochrome genes. The G. lovleyi strain SZ genome also harbored a 77 kbp plasmid carrying 15 out of the 24 genes involved in biosynthesis of corrinoid, likely related to this strains ability to degrade PCE to cis-DCE in the absence of supplied corrinoid (i.e., vitamin B₁₂). Although corrinoids are essential cofactors to RDases, the strictly organohalide-respiring
Dehalococcoides mccartyi strains are corrinoid auxotrophs and depend upon uptake of extracellular corrinoids via Archaeal and Bacterial salvage pathways. A
key corrinoid salvage gene in D. mccartyi, cbiZ, occurs at duplicated loci adjacent
to RDase genes and appears to have been horizontally-acquired from Archaea. These comparative genome analyses highlight RDase dependencies upon
corrinoids and also suggest mobile genomic elements (e.g., plasmids) are associated with organohalide respiration and corrinoid acquisition among OHRB. In summary, analyses of OHRB genomes promise to enable more complete
modeling of metabolic and evolutionary processes associated with the turnover of organohalides in anoxic environments. These efforts also expand knowledge of
biomarkers for monitoring OHRB activity in anoxic environments, and will improve our understanding of the fate of chlorinated contaminants.
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Ellegaard, Kirsten Maren, Lisa Klasson, Kristina Näslund, Kostas Bourtzis, and Siv G. E. Andersson. "Comparative Genomics of Wolbachia and the Bacterial Species Concept." Uppsala universitet, Molekylär evolution, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200821.
Full textAbstract:
The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally transmitted genes.
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Nakjang, Sirintra. "Comparative genomics for studying the proteomes of mucosal microorganisms." Thesis, University of Newcastle Upon Tyne, 2011. http://hdl.handle.net/10443/1265.
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A tremendous number of microorganisms are known to interact with their animal hosts. The outcome of the interactions between microbes and their animal hosts range from modulating the maintenance of homeostasis to the establishment of processes leading to pathogenesis. Of the numerous species known to inhabit humans, the great majority live on mucosal surfaces which are highly defended. Despite their importance in human health, little is known about the molecular and cellular basis of most host-microbe interactions across the tremendous diversity of mucosal-adapted microorganisms. The ever-increasing availability of genome sequence data allows systematic comparative genomics studies to identify proteins with potential important molecular functions at the host-microbe interface. In this study, a genome-wide analysis was performed on 3,021,490 protein sequences derived from 867 complete microbial genome sequences across the three domains of cellular life. The ability of microbes to thrive successfully in a mucosal environment was examined in relation to functional genomics data from a range of publicly available databases. Particular emphasis was placed on the extracytoplasmic proteins of microorganisms that thrive on human mucosal surfaces. These proteins form the interface between the complex host-microbe and microbe-microbe interactions. The large amounts of data involved, combined with the numerous analytical techniques that need to be performed makes the study intractable with conventional bioinformatics. The lack of habitat annotations for microorganisms further compounds the problem of identifying the microbial extracytoplasmic proteins playing important roles in the mucosal environments. In order to address these problems, a distributed high throughput computational workflow was developed, and a system for mining biomedical literature was trained to automatically identify microorganisms’ habitats. The workflow integrated existing bioinformatics tools to identify and characterise protein-targeting signals, cell surface-anchoring features, protein domains and protein families. This study successfully demonstrated a large-scale comparative genomics approach utilising a system called Microbase to harness Grid and Cloud computing technologies. A number of conserved protein domains and families that are significantly associated with a speiii iv cific set of mucosa-inhabiting microorganisms were identified. These conserved protein regions of which their functions were either characterised or unknown, were quite narrow in their coverage of taxa distribution, with only a few protein domains more widely distributed, suggesting that mucosal microorganisms evolved different solutions in their strategies and mechanisms for their survival in the host mucosal environments. Metabolic and biological processes common to many mucosal microorganisms included: carbohydrate and amino acid metabolisms, signal transduction, adhesion to host tissues or contents in mucosal environments (e.g. food remnants, mucins), and resistance to host defence mechanisms. Invasive or virulence factors were also identified in pathogenic strains. Several extracytoplasmic protein families were shared among prominent bacterial members of gut microbiota and microbial eukaryotes known to thrive in the same environment, suggesting that the ability of microbes to adapt to particular niches can be influenced by lateral gene transfer. A large number of conserved regions or protein families that potentially play important roles in the mucosa-microbe interactions were revealed by this study. Several of these candidates were proteins of unknown function. The identified candidates were subjected to more detailed computational analysis providing hypothesis for their function that will be tested experimentally in order to contribute to our understanding of the complex host-microbe interactions. Among the candidates of unknown function, a novel M60-like domain was identified. The domain was deposited in the Pfam database with accession number PF13402. The M60-like domain is shared amongst a broad range of mucosal microorganisms as well as their vertebrate hosts. Bioinformatics analyses of the M60-like domain suggested a potential catalytic function of the conserved motif as gluzincins metalloproteases. Targeting signals were detected across microbial M60-likecontaining proteins. Mucosa-related carbohydrate-binding modules (CBMs), CBM32 was also identified on several proteins containing M60-like domains encoded by known mucosal commensals and pathogens. The co-occurrence of the CBMs and M60-like domain, as well as annotated potential peptidase function unveiled a new functional context for the CBM, which is typically connected with carbohydrate processing enzymes but not proteases. The CBM domains linked with members of different protease families are likely to enable these proteases to bind to specific glycoproteins from host animals further highlighting the importance of proteases and CBMs (CBM32 and CBM5_12) in host-microbe interactions.
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Muller, Carolin Anne. "Comparative genomics of chromosome replication in sensu stricto yeasts." Thesis, University of Nottingham, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603592.
Full textAbstract:
Precise, complete and timely replication of eukaryotic genomes is a prerequisite to cell division. Each chromosome replicates in a defined temporal order that is dictated by the variable activation timings and efficiencies of replication origins. However, so far the mechanisms regulating origin activity have remained elusive. Replication origins are best understood in the budding yeast Saccharomyces cerevisiae. Powerful comparative genomic approaches are possible in budding yeasts due to the evolutionary range of sequenced genomes available and their tractability to genetic approaches. Previously, functional sequence elements at replication origins have been identified based upon their phylogenetic sequence conservation amongst closely related species of the sensu stricto group. To gain insight into the selective pressures contributing to this phylogenetic conservation, mutant strains with chromosomally inactivated origins were grown in competition with wild-type strains. Origin mutant strains did not have a growth defect compared to the wild-type, suggesting that the selective advantage conferred by evolutionary conserved origins is not the requirement for a rapid cell cycle time. To improve the reference sequence annotation, the S. cerevisiae genome was systematically screened for origin function, confirming more than 200 additional replication origins. The resulting comprehensive map of origin locations in S. cerevisiae was used to assess the accuracy of origin predictions from published studies and two newly developed techniques. These two approaches use high-throughput sequencing to either identify replication origin locations or measure replication dynamics genome-wide. Using the latter method on haploid and diploid S. cerevisiae strains showed that replication dynamics are independent of cell ploidy. Genome replication in divergent budding yeasts was investigated using a combination of replication timing profiles acquired with deep sequencing and plasmid-based assays. These analyses formed the basis for a comparative genomics approach, which revealed that the relative order of genome replication is conserved. A minority of replication origins with identical genomic locations show differences in activity between the analyzed species. To gain insight into the mechanisms underlying origin regulation, the replication dynamics of a hybrid between S. cerevisiae and its most distant relative in the sensu stricto group - S. bayanus - were measured. Replication origin function was found to be controlled by both local and global regulators .
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Godinez, Ricardo. "Comparative Genomics of the Major Histocompatibility Complex in Amniotes." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10685.
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The major histocompatibility complex region (MHC) is a multi gene family present in all jawed vertebrates, with a fundamental role in vertebrate immunity. More than two decades of studies have resulted in the characterization of over a dozen MHC regions, and models of evolution explaining that the MHC has gradually increased in size and gene content since its origins without addressing their genomic context or the environmental selective forces. Furthermore, a compelling reconstruction of the evolutionary history of the MHC has been hampered due to phylogenetic gaps and the absence of comparative phylogenetic methods applied to comparative genomics. Here I reconstruct 320 MY of MHC evolution using 42 amniote genomes using improved gene annotations, genomic alignments and phylogenetic algorithms to reconstruct the evolution of the MHC at three levels of phylogenetic resolution. The first one describes 25 MY of evolution of the primate MHC using eight Human and four non-Human primate MHC haplotypes. Results suggests that highly dense gene segments have a strikingly conserved gene organization, and six conserved and highly rearranging segments overlap genes that are most commonly associated to disease. Phylogenomic analysis implies that the MHC has remained stable in gene content and size, with significantly increased duplication rates in the primate ancestors. The second one describes 280 MY of MHC evolution through the first characterization of reptilian MHC region, which combines mammalian, reptilian, Bird and amphibian characteristics, which favors the hypothesis of the existence of a primordial MHC in which natural killer receptors, CD1 and lectin genes co-exist. The Anolis MHC expands our understanding of the origins of the exceptionally small Bird MHC regions and provides further information about the organization and size of the ancestral amniote MHC. The third one compares 42 amniote MHC regions and map gene duplications and losses to further evaluate the mode and tempo of the evolution of the region. Comparative phylogenetic methods imply that the genomic and environmental factors affect the diversification of MHC during 320 My of evolution.
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Edwards, Martin Tavis. "Comparative prokaryotic genomics : conservation of functional and spatial context." Thesis, Birkbeck (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428024.
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