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Cameron, Michael, and mcam@mc-mc net. "Efficient Homology Search for Genomic Sequence Databases." RMIT University. Computer Science and Information Technology, 2006. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20070509.162443.
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Genomic search tools can provide valuable insights into the chemical structure, evolutionary origin and biochemical function of genetic material. A homology search algorithm compares a protein or nucleotide query sequence to each entry in a large sequence database and reports alignments with highly similar sequences. The exponential growth of public data banks such as GenBank has necessitated the development of fast, heuristic approaches to homology search. The versatile and popular blast algorithm, developed by researchers at the US National Center for Biotechnology Information (NCBI), uses a four-stage heuristic approach to efficiently search large collections for analogous sequences while retaining a high degree of accuracy. Despite an abundance of alternative approaches to homology search, blast remains the only method to offer fast, sensitive search of large genomic collections on modern desktop hardware. As a result, the tool has found widespread use with millions of queries posed each day. A significant investment of computing resources is required to process this large volume of genomic searches and a cluster of over 200 workstations is employed by the NCBI to handle queries posed through the organisation's website. As the growth of sequence databases continues to outpace improvements in modern hardware, blast searches are becoming slower each year and novel, faster methods for sequence comparison are required. In this thesis we propose new techniques for fast yet accurate homology search that result in significantly faster blast searches. First, we describe improvements to the final, gapped alignment stages where the query and sequences from the collection are aligned to provide a fine-grain measure of similarity. We describe three new methods for aligning sequences that roughly halve the time required to perform this computationally expensive stage. Next, we investigate improvements to the first stage of search, where short regions of similarity between a pair of sequences are identified. We propose a novel deterministic finite automaton data structure that is significantly smaller than the codeword lookup table employed by ncbi-blast, resulting in improved cache performance and faster search times. We also discuss fast methods for nucleotide sequence comparison. We describe novel approaches for processing sequences that are compressed using the byte packed format already utilised by blast, where four nucleotide bases from a strand of DNA are stored in a single byte. Rather than decompress sequences to perform pairwise comparisons, our innovations permit sequences to be processed in their compressed form, four bases at a time. Our techniques roughly halve average query evaluation times for nucleotide searches with no effect on the sensitivity of blast. Finally, we present a new scheme for managing the high degree of redundancy that is prevalent in genomic collections. Near-duplicate entries in sequence data banks are highly detrimental to retrieval performance, however existing methods for managing redundancy are both slow, requiring almost ten hours to process the GenBank database, and crude, because they simply purge highly-similar sequences to reduce the level of internal redundancy. We describe a new approach for identifying near-duplicate entries that is roughly six times faster than the most successful existing approaches, and a novel approach to managing redundancy that reduces collection size and search times but still provides accurate and comprehensive search results. Our improvements to blast have been integrated into our own version of the tool. We find that our innovations more than halve average search times for nucleotide and protein searches, and have no signifcant effect on search accuracy. Given the enormous popularity of blast, this represents a very significant advance in computational methods to aid life science research.
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Smargon, Aaron Andrew. "An expanded search for RNA-programmable genomic engineering effectors." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/105959.
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Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>Cataloged from student-submitted PDF version of thesis.<br>Includes bibliographical references (pages 31-33).<br>A biocomputational pipeline was designed and implemented to mine through metagenomic datasets for novel Class 2 CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) single effectors, akin to the revolutionary genome-engineering tools Cas9 and Cpf1. Whereas previous search strategies relied on protein proximity to CRISPR-associated spacer acquisition proteins Cas1 and Cas2, this approach was seeded on CRISPR arrays alone. What resulted was the discovery of a potential new Class 2 CRISPR system, with two subtypes as characterized by distinct putative accessory proteins. Follow-up experimental work is required to assess the system's activity: first, in the presence and absence of the accessory protein; and second, as a single effector protein capable of precise genome engineering in prokaryotic and eukaryotic cells.<br>by Aaron Andrew Smargon.<br>S.M.
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Sheren, Jamie Elizabeth. "Identifying functional lox sequences: A genomic search and randomized libraries." Connect to online resource, 2007. 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:3273689.
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Lindblad, Kerstin. "Genomic studies of expanded trinucleotide repeats : focus on neuropsychiatric disorders /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980904lind.
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Skutas, Jorie L. "Microbial and Genomic Analysis of Environmental Samples in Search of Pathogenic Salmonella." NSUWorks, 2017. http://nsuworks.nova.edu/occ_stuetd/461.
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Salmonellosis or “food poisoning” is a foodborne infection brought on by the pathogen Salmonella from the ingestion of the bacterium on contaminated foods such as vegetables. Infection from Salmonella leads to the highest incidence of hospitalizations and deaths each year, compared to any other bacterial foodborne illness. South Florida is the second largest agricultural winter vegetable producer in the United States, and contamination of vegetables is often observed in preharvest practices. A hardy bacterium, Salmonella, has been shown to live up to 6 weeks in soil and water up to 42°C without a host.
The Florida Everglades is a tropical wetland that plays a large role in South Florida’s watershed. It can be divided into agricultural, conservation, and urban areas that connect Lake Okeechobee to Florida Bay by canals, swamps, and rivers. Inland canals tightly regulate water levels in South Florida as a means of flood control for residential and agricultural land. With the influences of anthropomorphic run off from agricultural and urban use, we hypothesized that microbial communities would significantly differ between three select sites in western (Collier county) versus three sites in more urban eastern Florida (Broward county): natural standing water, manmade drainage canal in agricultural areas, and manmade drainage canals in urban areas. We also hypothesized that pathogenic like Salmonella would be present in these habitats. Deep sequencing and ecological genetics analyses of the 16s rRNA V4 region yielded a total of 163,320 unique bacterial OTUs from a total of 139 samples collected monthly for one year in 2015 and part of 2016. Salmonella is not considered an abundant taxon within the microbial population.
With the knowledge that Salmonella resides within the microbial population isolates were cultured from soil and water samples that were taken monthly from each site using a modified version of the Food and Drug Administration Bacterial Analytical Methods manual (FDA-BAM). The culturing resulted in 234 isolates obtained and 31 different serovars of Salmonella. Culturing showed that Salmonella favored months with high standing water and high-water temperatures that would lead to the ideal environment for survival. The most commonly occurring isolates within the sample set are those associated with agricultural animals. Though Salmonella may be a rare taxon within the microbial population given the correct environmental conditions such as warm temperatures it is possible to observe Salmonella year round within the South Florida environment.
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Sigdel, Tara. "A Search for Zn(II) Metallochaperones in E. coli, Proteomic and Genomic Approaches." Miami University / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=miami1128394584.
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Rooney, Patrick Hugh. "A genomic approach to the study of chemoresistance." Thesis, University of Aberdeen, 2000. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU602009.
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This study evaluated comparative genomic hybridisation (CGH) as a tool to detect candidate regions of the genome associated with chemoresistance. Using a variation on conventional CGH, DNA from three cell lines that were resistant to thymidylate synthase (TS) inhibitors (tomudex [TDX] or 5-fluorouracil [5-FU]) and their sensitive parent cells were evaluated. In MCF-7 and H630, cells that were resistant to TDX, a specific TS inhibitor with no other known cytotoxic potential, only a single region of change (18p gain) was apparent. The third cell line H630R10, which was resistant to 5-FU, had changes in several genomic regions following the acquisition of resistance, including 18p. Gain in the chromosomal region containing the TS gene (18pll.32) was detected by CGH in all three resistant cell lines. However, additional novel regions of interest were identified in the cells that were resistant to 5-FU, a cytotoxic agent known to have several other modes of cytotoxicity besides TS inhibition. These results suggested that CGH is of potential use in the detection of regions of the genome involved in chemoresistance. Having shown the potential of CGH as a tool for assessing chemoresistance at the genomic level, steps toward clinical application of this technique were evaluated. A prerequisite for study in archival pathology samples was successful DNA extraction and universal amplification of tumour DNA from paraffin-embedded tumour sections for CGH analysis. Degenerate oligonucleotide primed - polymerase chain reaction (DOP-PCR) was performed on minute quantities (50ngs) of fresh cell line DNA (H630R10) and tumour DNA (osteosarcoma), as well as paraffin-embedded DNA from the same case. The results of these DOP-PCR CGH reactions were compared with conventional CGH using l|0.g quantities of fresh DNA from both H630R10 cell line and osteosarcoma. The CGH profiles of the conventional CGH and DOP-PCR CGH did not show a high level of concordance, only 55% of the gains and 83.3% of losses detected by conventional CGH were detected by DOP-PCR CGH The use of universal amplification by DOP-PCR in paraffin-embedded sections was not taken forward into clinical evaluation. A study of colorectal cancer (CRC) was initiated which involved the microdissection of 29 Dukes' C CRC tumours from fresh frozen material for CGH analysis. This conventional CGH analysis of CRC tumours involved assessing each tumour twice by reversal of fluorochromes. Only genomic regions that were detected as changed in both forward and reverse profiles were accepted. This approach detected several regions of genome as changed across the 29 tumours. In all, 108 gains (a mean number of 3.7 aberrations per tumour, range 1-12) and 85 losses (a mean number of 2.9 aberrations per tumour, range 0-11) were detected in the 29 tumours. CGH analyses identified certain chromosomal regions as more likely to be changed than others. The most frequent aberrations detected across the 29 tumours was a loss of chromosomal arm 18q, seen in 31% of the tumours assessed. Gain was also common at some sites throughout the genome, for example, gain of chromosomal arms, 13q and 20q was seen in 27.6% of cases. Mann-Whitney U tests investigating the association between specific chromosomal aberrations such as gain of 20q or loss of 18q and known markers of CRC tumourigenesis (p53, p27, p21, Rb, cyclin Dl, PCNA, P-catenin, e-cadherin, c-erbB-2, bcl2, EGFR and c-erbB-2) assessed by immunohistochemistry (IHC) in 29 tumours found no association. Testing of the total number of genomic aberrations detected (loss + gain = genetic grade) rather than the frequency of aberration at specific chromosomal loci also found no association with the CRC tumour markers. Finally, the association between the chromosomal aberrations detected by CGH was investigated in relation to patient survival. This thesis has demonstrated the value of a global approach to the study of chemoresistance and tumourigenesis through the application of powerful technology such as CGH.
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Berrutti, Paula Dandara da Silva. "Genomic search of transposable elementsand their implications for the variability of pest species of fruit culture." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2018. http://hdl.handle.net/10183/187236.
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Burkhart, Tandace L. "The Search for Novel Sponge genes: Comparative Analysis of Gene Expression in Multiple Sponges." NSUWorks, 2012. http://nsuworks.nova.edu/occ_stuetd/194.
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This project focuses on the use of sponge genetic transcripts in the form of expressed sequence tags (ESTs) readily available in Genbank to search for novel genes using bioinformatics analysis tools. Marine sponge species are known to house a diversity of marine microbes and are known as the ‘living fossils’ of the animal kingdom because of the large number of ancient genes they house. Genomic mining can be a useful tool in discovering these orthologous genes. This study utilized the techniques of genomic mining of 11 previously described sponge species transcripts. The results of this study provide a better understanding of the genomic structure of the organisms studied by creating a more detailed genetic map and examining a specific environmental snapshot of the genes in each sponge. Novel methods for dissecting beneficial information from large scale data sets available in genomic libraries utilizing bioinformatics search tool MGRAST were examined. The results of this study indicate that sponges house numerous genes that are likely to be evolutionary predecessors of genes in higher eukaryotes. Support was also given to the notion that microbial communities play a role in metabolic pathways of sponges.
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Sun, Wenhai. "Towards Secure Outsourced Data Services in the Public Cloud." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/84396.
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Past few years have witnessed a dramatic shift for IT infrastructures from a self-sustained model to a centralized and multi-tenant elastic computing paradigm -- Cloud Computing, which significantly reshapes the landscape of existing data utilization services. In truth, public cloud service providers (CSPs), e.g. Google, Amazon, offer us unprecedented benefits, such as ubiquitous and flexible access, considerable capital expenditure savings and on-demand resource allocation. Cloud has become the virtual ``brain" as well to support and propel many important applications and system designs, for example, artificial intelligence, Internet of Things, and so forth; on the flip side, security and privacy are among the primary concerns with the adoption of cloud-based data services in that the user loses control of her/his outsourced data. Encrypting the sensitive user information certainly ensures the confidentiality. However, encryption places an extra layer of ambiguity and its direct use may be at odds with the practical requirements and defeat the purpose of cloud computing technology. We believe that security in nature should not be in contravention of the cloud outsourcing model. Rather, it is expected to complement the current achievements to further fuel the wide adoption of the public cloud service. This, in turn, requires us not to decouple them from the very beginning of the system design. Drawing the successes and failures from both academia and industry, we attempt to answer the challenges of realizing efficient and useful secure data services in the public cloud. In particular, we pay attention to security and privacy in two essential functions of the cloud ``brain", i.e. data storage and processing. Our first work centers on the secure chunk-based deduplication of encrypted data for cloud backup and achieves the performance comparable to the plaintext cloud storage deduplication while effectively mitigating the information leakage from the low-entropy chunks. On the other hand, we comprehensively study the promising yet challenging issue of search over encrypted data in the cloud environment, which allows a user to delegate her/his search task to a CSP server that hosts a collection of encrypted files while still guaranteeing some measure of query privacy. In order to accomplish this grand vision, we explore both software-based secure computation research that often relies on cryptography and concentrates on algorithmic design and theoretical proof, and trusted execution solutions that depend on hardware-based isolation and trusted computing. Hopefully, through the lens of our efforts, insights could be furnished into future research in the related areas.<br>Ph. D.
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Ruppert, Ann-Kathrin [Verfasser], Peter [Akademischer Betreuer] Nürnberg, Peter [Akademischer Betreuer] Schneider, and Peter [Akademischer Betreuer] Kloppenburg. "Integrative functional genomic search for regulatory DNA sequence polymorphisms influencing DNA methylation and mRNA expression in hippocampal brain tissue / Ann-Kathrin Ruppert. Gutachter: Peter Nürnberg ; Peter Schneider ; Peter Kloppenburg." Köln : Universitäts- und Stadtbibliothek Köln, 2015. http://d-nb.info/1084872617/34.
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Zaharia, Alexandra. "Identification des motifs de voisinage conservés dans des contextes métaboliques et génomiques." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS275/document.
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Cette thèse s'inscrit dans le cadre de la biologie des systèmes et porte plus particulièrement sur un problème relatif aux réseaux biologiques hétérogènes. Elle se concentre sur les relations entre le métabolisme et le contexte génomique, en utilisant une approche de fouille de graphes.Il est communément admis que des étapes enzymatiques successives impliquant des produits de gènes situés à proximité sur le chromosome traduisent un avantage évolutif du maintien de cette relation de voisinage au niveau métabolique ainsi que génomique. En conséquence, nous choisissons de nous concentrer sur la détection de réactions voisines catalysées par des produits de gènes voisins, où la notion de voisinage peut être modulée en autorisant que certaines réactions et/ou gènes soient omis. Plus spécifiquement, les motifs recherchés sont des trails de réactions (c'est-à-dire des séquences de réactions pouvant répéter des réactions, mais pas les liens entre elles) catalysées par des produits de gènes voisins. De tels motifs de voisinage sont appelés des motifs métaboliques et génomiques.De plus, on s'intéresse aux motifs de voisinage métabolique et génomique conservés, c'est-à-dire à des motifs similaires pour plusieurs espèces. Parmi les variations considérées pour un motif conservé, on considère l'absence/présence de réactions et/ou de gènes, ou leur ordre différent.Dans un premier temps, nous proposons des algorithmes et des méthodes afin d'identifier des motifs de voisinage métabolique et génomique conservés. Ces méthodes sont implémentées dans le pipeline libre CoMetGeNe (COnserved METabolic and GEnomic NEighborhoods). À l'aide de CoMetGeNe, on analyse une sélection de 50 espèces bactériennes, en utilisant des données issues de la base de connaissances KEGG.Dans un second temps, un développement de la détection de motifs conservés est exploré en prenant en compte la similarité chimique entre réactions. Il permet de mettre en évidence une classe de modules métaboliques conservés, caractérisée par le voisinage des gènes intervenants<br>This thesis fits within the field of systems biology and addresses a problem related to heterogeneous biological networks. It focuses on the relationship between metabolism and genomic context through a graph mining approach.It is well-known that succeeding enzymatic steps involving products of genes in close proximity on the chromosome translate an evolutionary advantage in maintaining this neighborhood relationship at both the metabolic and genomic levels. We therefore choose to focus on the detection of neighboring reactions being catalyzed by products of neighboring genes, where the notion of neighborhood may be modulated by allowing the omission of several reactions and/or genes. More specifically, the sought motifs are trails of reactions (meaning reaction sequences in which reactions may be repeated, but not the links between them). Such neighborhood motifs are referred to as metabolic and genomic patterns.In addition, we are also interested in detecting conserved metabolic and genomic patterns, meaning similar patterns across multiple species. Among the possible variations for a conserved pattern, the presence/absence of reactions and/or genes may be considered, or the different order of reactions and/or genes.A first development proposes algorithms and methods for the identification of conserved metabolic and genomic patterns. These methods are implemented in an open-source pipeline called CoMetGeNe (COnserved METabolic and GEnomic NEighborhoods). By means of this pipeline, we analyze a data set of 50 bacterial species, using data extracted from the KEGG knowledge base.A second development explores the detection of conserved patterns by taking into account the chemical similarity between reactions. This allows for the detection of a class of conserved metabolic modules in which neighboring genes are involved
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Benedettini, Stefano <1983>. "Metaheuristics for Search Problems in Genomics - New Algorithms and Applications." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4403/.
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In this thesis we made the first steps towards the systematic application of a methodology for automatically building formal models of complex biological systems. Such a methodology could be useful also to design artificial systems possessing desirable properties such as robustness and evolvability.
The approach we follow in this thesis is to manipulate formal models by means of adaptive search methods called metaheuristics.
In the first part of the thesis we develop state-of-the-art hybrid metaheuristic algorithms to tackle two important problems in genomics, namely, the Haplotype Inference by parsimony and the Founder Sequence Reconstruction Problem. We compare our algorithms with other effective techniques in the literature, we show strength and limitations of our approaches to various problem formulations and, finally, we propose further enhancements that could possibly improve the performance of our algorithms and widen their applicability.
In the second part, we concentrate on Boolean network (BN) models of gene regulatory networks (GRNs). We detail our automatic design methodology and apply it to four use cases which correspond to different design criteria and address some limitations of GRN modeling by BNs. Finally, we tackle the Density Classification Problem with the aim of showing the learning capabilities of BNs.
Experimental evaluation of this methodology shows its efficacy in producing network that meet our design criteria.
Our results, coherently to what has been found in other works, also suggest that networks manipulated by a search process exhibit a mixture of characteristics typical of different dynamical regimes.
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Steinbeck, Rüdiger G. "Mitotic failure and genome stability in benign, premalignant and malignant human tissues /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980611stei.
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Mecham, Jesse L. "Jumpstarting phylogenetic searches /." Diss., CLICK HERE for online access, 2006. http://contentdm.lib.byu.edu/ETD/image/etd1403.pdf.
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Loh, Po-Ru. "Algorithms for genomics and genetics : compression-accelerated search and admixture analysis." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/83631.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Mathematics, 2013.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>Cataloged from student-submitted PDF version of thesis.<br>Includes bibliographical references (pages 133-139).<br>Rapid advances in next-generation sequencing technologies are revolutionizing genomics, with data sets at the scale of thousands of human genomes fast becoming the norm. These technological leaps promise to enable corresponding advances in biology and medicine, but the deluge of raw data poses substantial mathematical, computational and statistical challenges that must first be overcome. This thesis consists of two research thrusts along these lines. First, we propose an algorithmic framework, "compressive genomics," that accelerates bioinformatic computations through analysis-aware compression. We demonstrate this methodology with proof-of-concept implementations of compression-accelerated search (CaBLAST and CaBLAT). Second, we develop new computational tools for investigating population admixture, a phenomenon of importance in understanding demographic histories of human populations and facilitating association mapping of disease genes. Our recently released ALDER and MixMapper software packages provide fast, sensitive, and robust methods for detecting and analyzing signatures of admixture created by genetic drift and recombination on genome-wide, large-sample scales.<br>by Po-Ru Loh.<br>Ph.D.
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Ozturk, Ozgur. "Feature extraction and similarity-based analysis for proteome and genome databases." The Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1190138805.
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Kovaliovas, Viktoras. "Genomų palyginimo algoritmų tyrimas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2005. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2005~D_20050523_134443-96340.
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To understand evolution, and to discover how different species are related, gene order analysis is a useful tool. Problems in this area can usually be formulated in a combinatorial language. We regard genomes as signed, or unsigned permutations, and thus evolutionary operations like inversions (reversing the order of a segment of genes) are easy to describe combinatorially. A commonly studied problem is to determine the evolutionary distance between two species. This is estimated by several combinatorial distances between gene order permutations, for instance the inversion distance.
The main objective of this work was to survey the existing algorithms for genome comparison and to present new approach for solving this problem. The work led to these results:
- We have surveyed existing approaches of genome comparison, namely comparison by inversion distance in signed and unsigned cases. It appeared that sorting signed genomes by inversions is done in quadratic time, but sorting unsigned genomes by inversions is NP-hard.
- We have proposed the method of how to apply heuristic algorithms for sorting unsigned genomes by inversions.
- We have applied tabu search and genetic algorithm to solve the sorting unsigned genomes by inversions problem.
- We have experimentally proven, that the worst case solutions to sorting unsigned genomes by inversions found by heuristics (tabu search and genetic algorithm) are better then ones expected from best known approximating algorithm used for... [to full text]
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Wold, Håkon Hjelde. "Can Genome Information be used to Guide Evolutionary Search?" Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for datateknikk og informasjonsvitenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-23599.
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Uniform cellular automata have been evolved as phenotypes from zygotes using an extensive rule table as the genotype. This is used to simulate complex systems which could impact future hardware development and programming. This work falls within the field of Evolutionary and Developmental Systems (EvoDevo). Genome parameters are used in a genetic algorithm to try to reduce the number of generations needed to find a genome with a given complexity. Lambda parameter has been used inside the fitness function and produced promising results. Lambda has also been used to discard genomes before they are developed with poor results. Transition parameters are shown to be similar to lambda in predicting the trajectory length of a developing phenotype, but have yet to produce the same results. The genome usage has been used to control mutation with good results. The results of the work have provided more insight into how genome parameters work and what to not do when using them.
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Holley, Guillaume [Verfasser], and Jens [Akademischer Betreuer] Stoye. "Pan-genome Search and Storage / Guillaume Holley ; Betreuer: Jens Stoye." Bielefeld : Universitätsbibliothek Bielefeld, 2018. http://d-nb.info/1155302710/34.
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Bailey, David M. D. "Genome mapping in a search for a sex determining gene." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361752.
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Bhattaru, Srinivasa Aditya. "Design, testing, and validation of the search for Extra-Terrestrial Genomes instrument." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/119060.
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Thesis: S.M., Massachusetts Institute of Technology, Department of Aeronautics and Astronautics, 2018.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 75-78).<br>The development of any spaceflight instrument involves a systematic, iterative process of design, testing, and validation. This ensures that the system developed will meet the needs of stakeholders while minimizing costs and risks. Here, the needs for a life-detection instrument targeting nucleic acids are identified, the objectives for that instrument are determined, and system engineering analysis is used to demonstrate that a Search for Extra-Terrestrial Genomes instrument would fulfill those objectives and is feasible for a rover mission. Additionally, we show our design and build process for a testbed to rapidly prototype SETG components and subsystems, which has successfully automated nucleic acid extraction, sequencer loading, and parts of library preparation. We also experiment with thermal simulations and conduct a sequencing test at Martian conditions, using a custom built thermal vacuum chamber system. Finally, this thesis explores potential avenues for future development and identifies short term and long term engineering goals that would assist the SETG team in developing an instrument prototype.<br>by Srinivasa Aditya Bhattaru.<br>S.M.
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Keller, Brigitte D. "Search for new steroid hormone metabolizing enzymes functional genomics of the short chain dehydrogenase, reductase superfamily /." [S.l.] : [s.n.], 2006. http://mediatum2.ub.tum.de/doc/603773/document.pdf.
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Gardeux, Vincent. "Conception d'heuristiques d'optimisation pour les problèmes de grande dimension : application à l'analyse de données de puces à ADN." Phd thesis, Université Paris-Est, 2011. http://tel.archives-ouvertes.fr/tel-00676449.
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Cette thèse expose la problématique récente concernant la résolution de problèmes de grande dimension. Nous présentons les méthodes permettant de les résoudre ainsi que leurs applications, notamment pour la sélection de variables dans le domaine de la fouille de données. Dans la première partie de cette thèse, nous exposons les enjeux de la résolution de problèmes de grande dimension. Nous nous intéressons principalement aux méthodes de recherche linéaire, que nous jugeons particulièrement adaptées pour la résolution de tels problèmes. Nous présentons ensuite les méthodes que nous avons développées, basées sur ce principe : CUS, EUS et EM323. Nous soulignons en particulier la très grande vitesse de convergence de CUS et EUS, ainsi que leur simplicité de mise en oeuvre. La méthode EM323 est issue d'une hybridation entre la méthode EUS et un algorithme d'optimisation unidimensionnel développé par F. Glover : l'algorithme 3-2-3. Nous montrons que ce dernier algorithme obtient des résultats d'une plus grande précision, notamment pour les problèmes non séparables, qui sont le point faible des méthodes issues de la recherche linéaire. Dans une deuxième partie, nous nous intéressons aux problèmes de fouille de données, et plus particulièrement l'analyse de données de puces à ADN. Le but est de classer ces données et de prédire le comportement de nouveaux exemples. Dans un premier temps, une collaboration avec l'hôpital Tenon nous permet d'analyser des données privées concernant le cancer du sein. Nous développons alors une méthode exacte, nommée delta-test, enrichie par la suite d'une méthode permettant la sélection automatique du nombre de variables. Dans un deuxième temps, nous développons une méthode heuristique de sélection de variables, nommée ABEUS, basée sur l'optimisation des performances du classifieur DLDA. Les résultats obtenus sur des données publiques montrent que nos méthodes permettent de sélectionner des sous-ensembles de variables de taille très faible,ce qui est un critère important permettant d'éviter le sur-apprentissage
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Thompson, Katherine L. "Using ancestral information to search for quantitative trait loci in genome-wide association studies." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1372410951.
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Kusuma, Pradiptajati. "In search of Asian Malagasy ancestors in Indonesia." Thesis, Toulouse 3, 2017. http://www.theses.fr/2017TOU30109/document.
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L'Indonésie a été l'objet de la dispersion Austronésienne qui a débuté il y a environ 5000 ans depuis Taiwan, se propager à travers les Philippines et l'Indonésie, puis toucher l'Océanie à l'est, et à Madagascar à l'ouest. Malgré de nombreuses recherches en génétique sur la dispersion Austronésienne vers l'est, il y a très peu de données sur la dispersion vers l'ouest, laissant sans réponse de nombreuses questions, liées notamment au peuplement de Madagascar. Reposant sur l'analyse des données culturelles et biologiques, les populations d'Indonésie semblent avoir joué un rôle majeur dans la colonisation de Madagascar, le premier millénaire de notre ère. Cependant, le peu de populations Indonésiennes étudiées à ce jour n'a pas permis jusqu'à présent d'identifier la population indonésienne source. Dans ce présent travail, j'ai réalisé des études en génétique des populations de 12 populations Indonésiennes, qui à priori devraient éclairer l'histoire des migrations austronésiennes dans l'Océan Indien. Parmi elles sont inclus le Ma'anyan du sud-est de Bornéo qui sont les plus proches linguistiquement des Malgaches. En utilisant différents marqueurs génétiques, ma recherche a amélioré nos connaissances de la diversité génétique Indonésienne, et du lien génétique entre l'Indonésie et Madagascar. Résultats L'analyse des marqueurs uniparentaux (chr-Y et ADNmt) suggère que les Malgaches proviennent de plusieurs régions d'Indonésie, avec un lien privilégié avec le sud-est de Bornéo, le sud de Sulawesi et les îles de la Sonde. Etonnamment, les Ma'anyan partagent un nombre limité de lignées paternelles et maternelles avec les Malgaches, malgré leur proximité linguistique. Par ailleurs, en combinant l'analyse de fréquences des SNPs et l'analyse haplotypique à partir des données autosomales, il a été confirmé que la diversité génétique des Ma'anyan ne correspond pas à l'ancestralité asiatique des Malgaches. Cependant, en centrant l'analyse sur les populations du sud-est de Bornéo, l'origine de l'ancestralité asiatique des Malgaches est ancrée dans la population Banjar, un mélange de population Ma'anyan et Malaise, résultat des activités commerciales de l'empire Malais dans le sud-est de Bornéo, qui se sont poursuivies à travers l'océan Indien. Par ailleurs nos résultats ont aussi permis d'accroitre notre compréhension de la diversité génétique de l'Indonésie en identifiant (1) une nouvelle composante génétique austronésienne présente chez les Ma'anyan, et retrouvée à faible fréquence à travers l'Asie du Sud-Est, suggérant une plus grande complexité du modèle d'expansion austronésien dans la région et (2) le rôle joué par les nomades de la mer dans la structuration de la diversité génétique et les échanges entre populations dans l'Indonésie, soulignant l'histoire génétique complexe de populations suivant un mode de vie nomade<br>Indonesia hosts a wide range of linguistic, ethnic and genetic diversity, comprising ~600 ethnic groups and 700 living languages. Indonesia has facilitated the last substantial wave of human migration was the Austronesian dispersal ~5,000 years ago, which is thought to have originated in Taiwan. Its influence spread through Philippines and Indonesia, ultimately impacting a wide geographical area, from Remote Oceania in the east and to Madagascar in the west. Despite considerable genetic research on the eastward Austronesian expansion, there is little equivalent research on the western edge, leaving major issues unresolved regarding the settlement of Madagascar. Based on cultural and biological studies, it has been suggested that Indonesian peoples played a major role in the colonization of Madagascar from around the mid-first millennium CE (Current Era). However, poor geographical coverage of Indonesian populations has prevented the Indonesian source populations from being identified. Here, I performed human population genetic studies on 12 new Indonesian populations, which were a priori expected to shed light on the westward migration of Austronesians across the Indian Ocean. This includes the Ma'anyan ethnic group from Southeast Borneo, who are the closest linguistic siblings to modern Malagasy. Using different genetic markers (Y-chromosome SNPs, mitochondrial DNA and genome-wide SNPs), my research has improved the description of Indonesian genetic diversity, and investigated the genetic links between Indonesia and Madagascar. Results Uniparental markers (Y-chromosome and mtDNA) analyses suggest that Malagasy derive from multiple regional sources in Indonesia, with a focus on southeastern Borneo, southern Sulawesi and the Lesser Sunda islands. Interestingly, the Ma'anyan share limited paternal and maternal lineages with the Malagasy, despite their linguistic connection. Furthermore, combining SNP frequency and haplotype-based analyses from autosomal genome-wide data, it was confirmed that the genetic diversity of the Ma'anyan does not match the Asian ancestry of the Malagasy. However, by focusing on Southeast Borneo populations, strong support was found for an origin of the Asian ancestry of Malagasy among the people of Banjar, an admixed population of Ma'anyan and Malay, likely resulting from trading activities by the Malay Empire in Southeast Borneo, and later continuing across the Indian Ocean arena. These results increase our understanding of genetic diversity across Indonesia by 1) identifying the unique and undiscovered Austronesian genetic component carried by the Ma'anyan, which occurs at low levels across Island Southeast Asia and suggests a more complex model for the Austronesian expansion in this region, and 2) describing the role played by sea-nomads in structuring genetic diversity and exchanges in central Indonesia, thus revealing the complex genetic history of populations living this rare nomadic lifestyle
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Johnson, Andrew Danner. "Search for functional alleles in the human genome with focus on cardiovascular disease candidate genes." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1187018497.
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Feng, Xiaopeng. "Chicken growth hormone receptor and growth hormone : search for genetic variants which affect commercially important traits." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=42028.
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Chicken genomic DNA containing 5 kb of the 5$ sp prime$ end of the growth hormone (GH) receptor gene and 12 kb of the region up-stream was cloned and a restriction map was constructed. Using subcloned fragments as probes, a HindIII polymorphism was detected in both egg layer and in meat-type chickens. This polymorphic site was mapped at 7 kb up-stream of the coding region of the GH-receptor gene and a PCR assay for the polymorphism was developed to facilitate genotyping of large numbers of chickens.<br>Alleles of the GH-receptor gene and the GH gene were analyzed for association with traits in chicken strains of different genetic origins. In egg layers, association was significant for juvenile body weight, egg weight, feed consumption and feed efficiency for egg mass (P $<$ 0.05). In meat-type chickens, the GH-receptor allele associated with high juvenile body weight in egg layers was co-selected with leanness. A comparison of the genotype classes revealed that for several traits there was significant interaction between the GH and GH-receptor genotype. The results indicated that there are variants of the genes of the GH-axis which affect traits in White Leghorns and that the effect of a genetic variation in one gene may depend on the variation in another gene.
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Forgetta, Vincenzo. "Systematic search for Salmonella-susceptibility quantitative trait loci in the chicken using a whole genome scan approach." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33758.
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The goal of this project is to identify QTL involved in Salmonella -susceptibility in the chicken. Salmonellosis is one of the most common causes of food poisoning in humans and is frequently caused by the ingestion of Salmonella-contaminated poultry products. Identification of QTL responsible for Salmonella-susceptibility may lead to more efficient control strategies, and selection against genes that may lead to increased risk of transmission. The genome scan was performed on a selection of 425 backcross progeny, (W1 x C) F1 x C, derived from C Salmonella-susceptible and W1 Salmonella-resistant chickens. The 425 backcross birds were phenotyped for their susceptibility to infection with Salmonella Typhimurium. A collection of 160 fluorolabelled microsatellite markers (FAM, TET, and HEX) was used to scan the chicken genome, which is 3800cM in size (1.2 x 109 bp) and consists of 39 linkage groups, 9 chromosomes and 30 microchromosomes. We first tested the available microsatellite markers for informativeness in C and W1 chicken lines. In addition, we also determined the allele lengths and PCR product intensity (qualitatively) to facilitate pooling of markers during electrophoresis. PCR reaction mixtures were prepared using a Packard MultiProbe II Robotic System and Minitrak to pipette DNA-PCR Master mix and primer mix into microtiter plates. PCR products were then pooled and analyzed on Perkin-Elmer ABI Prism 3700 DNA Analyzers. Analysis of informative microsatellite markers on the backcross panel resulted in the detection of two loci, one on Chromosome 7 carrying NRAMP1, and the other on microchromosome E41W17 carrying TLR4, linked to resistance to Salmonella infection in chickens.
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Zhang, Youming. "A genome-wide search for asthma-associated quantitative traits loci in a mouse model of allergic asthma." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312554.
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Cénac, Peggy. "Étude statistique de séquences biologiques et convergence de martingales." Toulouse 3, 2006. http://www.theses.fr/2006TOU30065.
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Le système dynamique Chaos Game Representation associe à une suite de lettres dans un alphabet fini, une mesure empirique sur un ensemble. Fournit-elle plus d'information que les méthodes de comptage de mots classiques ? A partir d'une caractérisation basée sur la CGR, on propose une nouvelle famille de tests donnant l'ordre d'une chaîne de Markov homogène. On définit ensuite une construction d'arbres digitaux de recherche, inspirés par la CGR, en insérant successivement les préfixes retournés d'une chaîne de Markov. On montre que les longueurs des branches critiques se comportent, au premier ordre, comme si les séquences insérées étaient indépendantes entre elles. La dernière partie est consacrée à l'étude de la convergence presque sûre des moments normalisés de tout ordre de martingales vectorielles dans le théorème de la limite centrale presque sûr. Les résultats sont appliqués aux erreurs d'estimation et de prédiction dans les régressions linéaires et les processus de branchement<br>The Chaos Game Representation is a dynamical system which maps a sequence of letters taken from a finite alphabet onto an empirical measure on a set. We show how the CGR can be used to characterize the order of an homogeneous Markov chain and to define a new family of tests. Then we propose a construction of Digital Search Trees, inspired from the CGR, by successively inserting all the returned prefixes of a Markov chain. We give the asymptotic behavior of the critical lengths of paths, which turns out to be, at first order, the same one as in the case of DST built from independent Markov chains. A last part deals with properties of almost sure convergence of vectorial martingales. Under suitable regularity conditions on the growing process, we establish the convergence of normalized moments of all orders in the almost sure central limit theorem. The results are applied to the cumulated errors of estimation and prediction in linear regression models and branching processes
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Ross-Adams, Helen. "A genome-wide association study into ischaemic stroke using DNA pools and microarrays." Thesis, University of Aberdeen, 2006. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU222719.
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The main aim of this project was to identify likely candidate genes in ischaemic stroke from a population in North-East Scotland. SNP allele frequencies were investigated for significant differences between case and control pools to identify chromosomal regions likely to contain relevant genes. In this way, 43 candidate genes for ischaemic stroke were identified. Two had previously been found by other studies (ALOX5AP and PDE4D), and several interact with each other in a particular biochemical pathway. Moreover, the majority of genes identified could be grouped into four main disease processes – lipid metabolism, atherosclerosis, inflammation and apoptosis. These are all either known risk factors for, or characteristic of, Stroke and therefore strengthen our confidence in these results. In a separate study, polymorphisms in two candidate genes (PPP1R3, implicated in type II diabetes, and PLAT, involved in the development of stroke) were selected for individual grouping genotyping in available samples on the basis of previous studies and literature searches. Results were conflicting: no association with stroke sub-type was found for any polymorphism in the PLAT gene, while only one PPP1R3 SNP was significantly reduced in small and large vessel disease (but not cardio-embolic) stroke cases compared to controls. On the other hand, a common ATTTA deletion was associated with cardio-embolic strokes. Haplotype analysis in PPP1R3 showed one combination to be more frequent in cases overall than controls. These experiments highlighted the complex nature of stroke genetics, and also emphasised the usefulness of studying intermediate phenotypes to identify the genetic basis of common, complex disorders. In addition, DNA pools combined with microarrays are a powerful, efficient means by which to identify novel candidate genes relatively quickly.
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Gaspar, Manuel Augusto Ribeiro. "Automatic system for approximate and noncontiguous DNA sequences search." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/23810.
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Mestrado em Engenharia Eletrónica e Telecomunicações<br>A capacidade de efectuar pesquisas de sequências de ADN similares a outras
contidas numa sequência maior, tal como um cromossoma, tem um
papel muito importante no estudo de organismos e na possível ligação entre
espécies diferentes.
Apesar da existência de várias técnicas e algoritmos, criados com o intuito
de realizar pesquisas de sequência, este problema ainda está aberto ao desenvolvimento
de novas ferramentas que possibilitem melhorias em relação
a ferramentas já existentes.
Esta tese apresenta uma solução para pesquisa de sequências, baseada em
compressão de dados, ou, mais especificamente, em modelos de contexto finito, obtendo uma medida de similaridade entre uma referência e um alvo.
O método usa uma abordagem com base em modelos de contexto finito para
obtenção de um modelo estatístico da sequência de referência e obtenção
do número estimado de bits necessários para codificação da sequência alvo,
utilizando o modelo da referência.
Ao longo deste trabalho, estudámos o método descrito acima, utilizando,
inicialmente, condições controladas, e, por m, fazendo um estudo de
regiões de ADN do genoma humano moderno, que não se encontram em
ADN ancestral (ou se encontram com elevado grau de dissimilaridade).<br>The ability to search similar DNA sequences with relation to a larger sequence,
such as a chromosome, has a really important role in the study of
organisms and the possible connection between di erent species.
Even though several techniques and algorithms, created with the goal of
performing sequence searches, already exist, this problem is still open to the
development of new tools that exhibit improvements over currently existent
tools.
This thesis proposes a solution for sequence search, based on data compression,
or, speci cally, nite-context models, by obtaining a measure of
similarity between a reference and a target. The method uses an approach
based on nite-context models for the creation of a statistical model of the
reference sequence and obtaining the estimated number of bits necessary
for the codi cation of the target sequence, using the reference model.
In this work we studied the above described method, using, initially, controlled
conditions, and, nally, conducting a study on DNA regions, belonging
to the modern human genome, that can not be found in ancient DNA
(or can only be found with high dissimilarity rate).
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Milanius, Michelle, and Sofie Kullman. "Utnyttjar konsumenter möjligheten att agera rationellt? : En uppsats om konsumenters sökbeteende inför ett köp med avseende på irrationella köpbeslut eller möjliggörandet av rationella köpbeslut genom informationssökningsprocessen." Thesis, Örebro universitet, Handelshögskolan vid Örebro Universitet, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-34752.
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The buying decision process describes how the consumer makes a purchase decision through a rational process (Markin, 1979) and an understanding for how consumers make a purchase decision can according to Sands et al. (2010) be obtained by increased knowledge for the information search process (the second part of the buying decision process) before a purchase. Today’s society offers great opportunity to obtain information (Rahim & Clemens, 2012; Bawden & Robinson, 2009) and by that there are in other words good opportunities for a rational acting by the consumers. However, there are factors working against that consumers act rationally and seek information prior to their purchases primarily in the form of the concept of information overload (Bawden & Robinson, 2009) which claims that consumers are limited in their information search because there is too much information but also other factors such as lack of time (Wood & Neal, 2009) and ability to find information (Slegers et al. 2012) are believed to affect the information search process. The purpose of this essay is to describe the information search behavior of consumers prior to a purchase considering irrational purchase decisions or the possibility of rational purchase decisions linked to product category and age because these variables are assumed to have an impact on the information search behavior prior to a purchase (Nelson, 1970; Phillips & Sternthal, 1977; Sledgers et al., 2012). The method applied in this essay is structured interviews conducted in a shopping center in the central parts of Örebro and the participating respondents are consumers who just made a purchase. The results of the study indicate that the majority of the consumers are making irrational purchase decisions and that they therefore do not use the opportunity to act rationally, although today’s society provide good opportunities. The information search behavior doesn’t seem to depend on product category except that the information sources used differ among categories. The result also shows that younger consumers search more information in comparison with older consumers. Another finding is that neither ability to find information, lack of time or information overload seem to be reasons for that the majority of the consumers have not searched for information and nor do it seem to be the reason for why the consumers that do search for information stop to search. That they are not seeking seems instead to be because they feel that they know enough about the kind of product they have bought and the main reason that those who search stop to search is that they feel that they have found enough information to make a purchase decision. Key words: Consumer behavior, purchase decisions, the buying decision process, information search, rationality, irrationality, search goods, experience goods, information overload
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Morra, Erica, and Lisa Zenker. "Chapter 1: In Search of Innate Leadership : Discovering, Evaluating and Understanding Innateness." Thesis, Linnéuniversitetet, Institutionen för organisation och entreprenörskap (OE), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-34622.
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Every individual is born with different natural competencies that can be honed by both voluntary and involuntary environmental stimuli. The response our genotype decides to make, if any, towards those stimuli, determines how well our competencies develop. Each person’s coding and variations of genes will result in unique qualities in their phenotype, or physical structure. As a result, a person has various traits that are displayed through their behavior. DNA is genetically shown to express itself through traits by up to 75%. This leaves a sort of buffer of around 25%. This region is available for us to adapt to our environmental stimuli. Your innate qualities will not reach their full potential without stimulation from the environment, in a leadership case, with education and training and therefore it can be argued that environmental exposure is necessary to fully expose the potentials and capabilities of an individual, rather than instill a new skill or develop a talent that was not existent before. Innate leadership is not a permanent state, on the contrary, it is a continuously adaptive situation demanding contextual evolutionary changes or resignation from the subject occupying the role. When the needs and demands of a society or era outweigh the relevance of the innate leaders' traits and competencies, an evolution of leadership is needed to maintain a positive relationship between all parties involved. As a result, the innate leader will begin to lose their innateness in their role and unless they evolve and adapt (because the two actions are not the same) to new contextual needs, their tenure as leader will begin to be detrimental and counter-functional. What we want to put forward is a real, universal and constructive understanding of what makes a human happy, motivated and productive and how an innate person in context is a much better solution in the short and long run, for those around them when put to a task.
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Paulino, Rosangela Clara. "Detecção molecular de Giardia sp em amostras fecais e água : extração de DNA genomico, PCR e RFLP /." oai:ufpr.br:234179, 2005. http://200.17.209.5:8000/cgi-bin/gw_42_13/chameleon.42.13a?host=localhost%201111%20DEFAULT&sessionid=VTLS&function=CARDSCR&search=KEYWORD&pos=1&u1=12101&t1=234179.
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Orientadora : Vanete Thomaz Soccol<br>Tese (doutorado) - Universidade Federal do Paraná, Setor de Tecnologia, Programa de Pós-Graduaçao em Processos Biotecnológicos. Defesa: Curitiba, 2005<br>Inclui bibliografia<br>Área de concentração: Saude humana e animal
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Sung, Po Yi, and 宋柏誼. "Genomic DNA Sequence Visualization and Similarity Search." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/91517210134622504786.
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碩士<br>國立中正大學<br>通訊工程研究所<br>91<br>Genomic DNA sequences can been represented as long text data composed of alphabets A, C, T and G. These sequences present visualization challenges due to their length and complexity. In this paper, we proposed a visual technique called VBP (Visualization by Pentahedrons) algorithm to visualize and analyze similarity of DNA sequences. Here, a Markov chain model is employed to calculate the state transition probabilities of DNA sequences and map them into four different pentahedrons. According to these four pentahedrons, a three-dimensional trajectory can be drawn to represent the formation of DNA sequence in a global view.
For speeding up the similar DNA sequence search process, a content-based retrieval technique is proposed to search the similar DNA sequences against the DNA sequence database. This technique employed Peano scan method and Fourier Transformation to transfer 1D DNA nucleotide sequences into 2D far-field patterns. Then, PCA algorithm is used to extract features for effective DNA sequences retrieval. By combining proposed visualization and similarity search technologies, the functions and similarity of DNA sequences will be fast discriminated.
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Lin, Heshan. "High performance parallel and distributed genomic sequence search." 2009. http://www.lib.ncsu.edu/theses/available/etd-03132009-172048/unrestricted/etd.pdf.
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Bhavsar, Rajul D. "Search-Optimized Disk Layouts For Suffix-Tree Genomic Indexes." Thesis, 2011. http://etd.iisc.ernet.in/handle/2005/2124.
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Over the last decade, biological sequence repositories have been growing at an exponential rate. Sophisticated indexing techniques are required to facilitate efficient searching through these humongous genetic repositories. A particularly attractive index structure for such sequence processing is the classical suffix-tree, a vertically compressed trie structure built over the set of all suffixes of a sequence. Its attractiveness stems from its linearity properties -- suffix-tree construction times are linear in the size of the indexed sequences, while search times are linear in the size of the query strings.
In practice, however, the promise of suffix-trees is not realized for extremely long sequences, such as the human genome, that run into the billions of characters. This is because suffix-trees, which are typically an order of magnitude larger than the indexed sequence, necessarily have to be disk-resident for such elongated sequences, and their traditional construction and traversal algorithms result in random disk accesses. We investigate, in this thesis, post-construction techniques for disk-based suffix-tree storage optimization, with the objective of maximizing disk-reference locality during query processing. We begin by focusing on the layout reorganization in which the node-to-block assignments and sequence of blocks are reworked. Our proposed algorithm is based on combining the breadth-first layout approach advocated in the recent literature with probabilistic techniques for minimizing the physical distance between successive block accesses, based on an analysis of node traversal patterns. In our next step, we consider techniques for reducing the space overheads incurred by suffix-trees. In particular, we propose an embedding strategy whereby leaf nodes can be completely represented within their parent internal nodes, without requiring any space extension of the parent node's structure.
To quantitatively evaluate the benefits of our reorganized and restructured layouts, we have conducted extensive experiments on complete human genome sequences, with complex and computationally expensive user queries that involve finding the maximal common substring matches of the query strings.
We show, for the first time, that the layout reorganization approach can be scaled to entire genomes, including the human genome. In the layout reorganization, with careful choice of node-to-block assignment condition and optimized sequence of blocks, search-time improvements ranging from 25% to 75% can be achieved with respect to the construction layouts on such genomes. While the layout reorganization does take considerable time, it is a one-time process whereas searches will be repeatedly invoked on this index. The internalization of leaf nodes results in a 25% reduction in the suffix-tree space occupancy. More importantly, when applied to the construction layout, it provides search-time improvements ranging from 25% to 85%, and in conjunction with the reorganized layout, searches are speeded up by 50% to 90%. Overall, our study and experimental results indicate that through careful choice of node implementations and layouts, the disk access locality of suffix-trees can be improved to the extent that upto an order-of-magnitude improvements in search-times may result relative to the classical implementations.
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Riascos, John Jaime. "A genomic-based search for novel soybean (Glycine max L.) allergens." 2009. http://www.lib.ncsu.edu/theses/available/etd-12172008-120356/unrestricted/etd.pdf.
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Mosig, Axel, Katrin Sameith, and Peter F. Stadler. "Fragrep: An Efficient Search Tool for Fragmented Patterns in Genomic Sequences." 2006. https://ul.qucosa.de/id/qucosa%3A32010.
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Many classes of non-coding RNAs (ncRNAs; including Y RNAs, vault RNAs, RNase P RNAs, and MRP RNAs, as well as a novel class recently discovered in Dictyostelium discoideum) can be characterized by a pattern of short but well-conserved sequence elements that are separated by poorly conserved regions of sometimes highly variable lengths. Local alignment algorithms such as BLAST are therefore ill-suited for the discovery of new homologs of such ncRNAs in genomic sequences. The Fragrep tool instead implements an efficient algorithm for detecting the pattern fragments that occur in a given order. For each pattern fragment, the mismatch tolerance and bounds on the length of the intervening sequences can be specified separately. Furthermore, matches can be ranked by a statistically well-motivated scoring scheme.
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Bataille, Alain R. "Genome wide search for glycine metabolism genes." Thesis, 2003. http://spectrum.library.concordia.ca/2260/1/MQ83846.pdf.
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The yeast Saccharomyces cerevisiae uses glycine for the synthesis of activated one-carbon units and nitrogen metabolism. The homozygous diploid set of deletion strains includes strains deleted from all the S. cerevisiae non-essential genes (about 4700). This deletion set was screened for strains exhibiting a growth phenotype when glycine was used as the sole nitrogen source (Gmin medium). This screen identified a total of 321 strains. Within the 321 strains, 250 showed a growth defect on Gmin (G- phenotype) whereas 71 exhibited better growth on Gmin (G+ phenotype). Further high-density colony-array analyses established the growth profile for each of the 321 strains on ten different media. These growth profiling experiments identified genes important for various aspects of glycine metabolism. For example vesicular transport from the plasma membrane to the multivesicular body compartment was important for growth in media containing high concentrations of glycine. This suggests that the general amino acid permease (Gap1p) must be targeted to the vacuole for degradation to prevent glycine toxicity. Growth profiling also confirmed the importance of the mitochondrial compartment for glycine metabolism and defined the functional role of CEM1 and YJL046W for lipoate metabolism. This study therefore validated the use of growth profiling data generated using high density colony assays for the study of eukaryotic gene function.
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Abhinav, K. V. "Further Structural Studies on Jacalin and Genomics Search for Mycobacterial and Archeal Lectins." Thesis, 2016. http://etd.iisc.ernet.in/handle/2005/2858.
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This thesis consists of two parts. The first part is concerned with further structural and related studies of jacalin, one of the two lectins found in jack fruit seeds. The second part deals with the search of mycobacterial and archeal genomes for lectins.
The β-prism I fold was identified as a lectin fold through the X-ray analysis of jacalin way back in 1996. Subsequent structural studies on jacalin are described in the first chapter in context of the overall efforts on lectins with particular reference to those on lectins with β-prism I fold. The structure of jacalin has been thoroughly characterized through the analysis of several crystals. The extended binding site of the lectin, made up of the primary binding site and secondary sites A and B, has also been characterized through studies on different jacalin-sugar complexes. However, nuances of jacalin-carbohydrate interactions remain underexplored with respect to two specific issues. The first issue is concerned with the structural basis for the lower affinity of jacalin for β-substituted sugars. The second has to do with the influence of the anomeric nature of the glycosidic linkage on the location of the reducing and non-reducing sugars in disaccharides when interacting with jacalin. Part of the work described in the thesis addresses these two issues.
It was surmised that the lower affinity of β-galactosides to jacalin as compared to α-galactosides, is caused by steric interactions of the substituents in the former with the protein. This issue is explored both energetically and structurally in Chapter 2 using appropriately derivatized monosaccharide complexes of jacalin. It turns out that the earlier surmise is not correct. The interactions of the substituent with the binding site remain essentially the same irrespective of the anomeric nature of the substitution. This is achieved through a distortion of the sugar ring in β-galactosides. The difference in energy, and therefore affinity, is caused by the distortion of the sugar ring in β-galactosides. The elucidation of this unprecedented distortion of the ligand as a strategy for modulating affinity is of general interest. The crystal structures also provide a rationale for the relative affinities of the different carbohydrate ligands to jacalin.
The crystal structures of jacalin complexed with α-linked oligosaccharides Gal α-(1,4) Gal and Gal α-(1,3) Gal β-(1,4) Gal, as described in Chapter 3, have been determined with the primary objective of exploring the effect of linkage on the location of reducing and non-reducing sugars in the extended binding site of the lectin, an issue which has not been studied thoroughly. Contrary to the earlier surmise based on simple steric considerations, the two structures demonstrate that α-linked sugars can bind to jacalin with non-reducing sugar at the
primary binding site. This is made possible substantially on account of the hitherto underestimated plasticity of a non-polar region of the extended binding site. Modelling studies involving conformational search and energy minimization, along with available crystallographic and thermodynamic data, indicate a strong preference for complexation with Gal β-(1,3) Gal with the reducing Gal at the primary site, followed by that with Gal α-(1,3) Gal, with the reducing or non-reducing Gal located at the primary binding site. This observation is in consonance with the facility of jacalin to bind mucin type O-glycans containing T-antigen core.
Crystal structures of jacalin in complex with GlcNAc β-(1,3) Gal-β-OMe and Gal β-(1,3) Gal-β-OMe have also been described in Chapter 4. The binding of the ligands to jacalin is similar to that of analogous α-substituted disaccharides. However, the β-substituted β-(1,3) linked disaccharides get distorted at the anomeric centre and the glycosidic linkage. The distortion results in higher internal energies of the ligands leading to lower affinity to the lectin. This confirms the possibility of using ligand distortion as a strategy for modulating binding affinity. Unlike in the case of β-substituted monosaccharides bound to jacalin, where a larger distortion at the anomeric centre was observed, smaller distortions are distributed among two centres in the structures of the two β-substituted β-(1,3) linked disaccharides presented here. These disaccharides, like the unsubstituted and α-substituted counterparts, bind jacalin with the reducing Gal at the primary binding site, indicating that the lower binding affinity of β-substituted disaccharides is not enough to overcome the intrinsic propensity of Gal β-(1,3) Gal based disaccharides to bind jacalin with the reducing sugar at the primary site.
Although originally isolated from plants, lectins were also found subsequently in all forms of life, including bacteria. Studies on microbial lectins have not been as extensive as on those from plants and animals, although there have been some outstanding individual investigations on bacterial toxins like ADP-ribosylating toxins and neurotoxins. In addition to bacterial toxins, adhesins, β-trefoil lectins and cyanobacterial lectins form other important subgroups which have been explored using crystallography. Features pertaining to their three dimensional folds, carbohydrate specificity and biological properties are described in Chapter 5, to set the stage for the work discussed in the second part of the thesis. Studies on mycobacterial lectins were unexplored until work was initiated in the area in this laboratory some years ago. One of the lectins, identified on the basis of a bioinformatics search of M. tuberculosis H37Rv genome was cloned, expressed and crystallized. Also cloned, expressed and crystallized is another lectin from M. smegmatis. Biophysical and modelling studies were carried out on the full length protein containing this lectin. However, systematic efforts on mycobacterial lectins were conspicuous by their absence. The first chapter (Chapter 6) in the second part of the thesis is concerned with a genomic search for lectins in mycobacterial genomes. It was also realized that hardly anything is known about archeal lectins. Therefore, as discussed in the final chapter, a genomic search for archeal lectins was undertaken.
Sixty-four sequences containing lectin domains with homologs of known three-dimensional structure were identified through a search of mycobacterial genomes and are described in detail in Chapter 6. They appear to belong to the β-prism II, the C-type, the Microcystis virdis (MV), and the β-trefoil lectin folds. The first three always occur in conjunction with the LysM, the PI-PLC, and the β-grasp domains, respectively while mycobacterial β-trefoil lectins are unaccompanied by any other domain. Thirty heparin binding hemagglutinins (HBHA), already annotated, have also been included in the study although they have no homologs of known three-dimensional structure. The biological role of HBHA has been well characterized. A comparison between the sequences of the lectin from pathogenic and non-pathogenic mycobacteria provides insights into the carbohydrate binding region of the molecule, but the structure of the molecule is yet to be determined. A reasonable picture of the structural features of other mycobacterial proteins containing one of the four lectin domains can be gleaned through the examination of homologous proteins, although the structure of none of them is available. Their biological role is yet to be elucidated. The work presented here is among the first steps towards exploring the almost unexplored area of the structural biology of mycobacterial lectins.
As mentioned in Chapter 7, forty six lectin domains, which have homologues among well established eukaryotic and bacterial lectins of known three dimensional structure, have been identified through a search of 165 archeal genomes using a multi-pronged approach involving domain recognition, sequence search and analysis of binding sites. Twenty one of them have the 7-bladed β-propeller lectin fold while 16 have the β-trefoil fold and 7 the legume lectin fold. The remainder assumes the C-type lectin, the β-prism I and the tachylectin folds. Acceptable models for almost all of them could be generated using the appropriate lectins of known three dimensional structure as templates, with binding sites at one or more expected locations. The work represents the first comprehensive bioinformatics study of archeal lectins. The presence of lectins with the same fold in all domains of life indicates their ancient origin well before the divergence of the three branches. Further work is necessary to identify archeal lectins which have no homologues among eukaryotic and bacterial species.
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Stinson, E. O. "Implementation of vectorbase components ensEMBL genome browser, search , and database tools /." 2007. http://etd.nd.edu/ETD-db/theses/available/etd-09262007-153616/.
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Garvilles, Ronald-Garingalao, and 蓋羅納. "Genome-wide methylation pattern search in Prader-Willi Syndrome (PWS) patients." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/59827189279715437068.
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碩士<br>中原大學<br>生物科技研究所<br>99<br>Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by lack of functional paternal copy of 15q11-q13. Epigenetic aberrations due to genomic imprinting defect leads to the absence expression of paternally-inherited genes. This study aims to provide an overview of the methylation status of the whole-genome among PWS patients. A novel method PCR Selective Suppression Hybridization (PSSH) was employed to screen the putative genes that are differentially methylated among PWS patients but not in normal individuals. This method utilizes hybridization of methylated-non-biotin labeled DNA and unmethylated-biotin-labeled DNA from the PWS patient and mother, respectively, after subsequent bisulfite treatment, USER enzyme cleavage, labeling with biotin dCTP and separation by streptavidin. After successful screening of two families, several genes and gene clusters were identified that could possibly link to PWS after comprehensive analyses using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Pathway Interaction Database (PID): CREBBP, RRM1, HPP1 and XRCC6. Based on the previous published results, these candidate genes were found to have cross-talk mechanisms that link between DNA methylation and histone covalent modifications. From the confirmed PWS-related genes based on OMIM (NCBI), co-regulation of androgen receptor activity and E2F transcription factor network pathways could be candidate related pathways on the screened putative genes. In order to establish these hypothetical results, more PWS samples are needed for the analysis; and will be confirmed using real-time PCR (qPCR), methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP).
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Chen, Ko-Fan, and 陳克帆. "Whole Genome Search of Candidate Hypoxia Response Genes by Bioinformatic Methodology." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/70822334854372391625.
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碩士<br>國立成功大學<br>生理學研究所<br>93<br>Hypoxia is the reduction of environmental oxygen In absent of oxygen, hypoxia inducible factor-1 a (HIF-1a) dimerizes with HIF-1b and binds to the hypoxia response element (HRE) on the target DNA sequence. HIF-1a regulated genes have been found to be involved in cell proliferation, angiogenesis, glycolysis, apoptosis, and tumor formation. The HRE with a short core sequence “RCGTG” is necessary but not sufficient to be bound by HIF-1a. The flanking region also determines the binding activity. Accordingly, the 20 well known HREs were retrieved, aligned, and built up a hidden Markov model based HRE profile. The HMM-based HRE profile was used to search candidate HRE on the promoter region of human and mouse genes. 8170 human genes and 6477 mouse genes were identified by the cutoff score -1.8. About one-third of putative these HIF-1a regulated genes are conserved between human and mouse genome. The expression profiles of randomly picked fifty genes were investigated at various time points after DFO mimic hypoxia treatment. The regulation rate of the genes with positive score is 91%. This indicates that about 2500 human genes and 1600 mouse genes could be regulated by HIF-1a. In analysis of regulation pattern the candidate genes were regulated consistently among different cells or were specifically expressed and/ or regulated in one cell. For the time course analysis, the genes regulated by hypoxia can be further classified into one of early, delay, or biphasic category. The regulation patterns are similar in hypoxia and DFO treatment suggesting that DFO is a proper hypoxia mimetic. By detecting intra nuclear HIF-1a protein and in vivo binding of HIF-1a on the candidate HRE, it was demonstrated the altered RNA expression in candidate genes under chemical or true hypoxia is correlated with nuclear HIF-1a protein level and the binding activity. Put all together, this study demonstrated a high throughput screening and verification approach in understanding the whole picture of gene regulation mediated by hypoxia.
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Wittig, Michael David. "Search for selection pressures associated with aggregation propensity following whole genome duplication in S.cerevisiae." Thesis, 2011. http://hdl.handle.net/2152/ETD-UT-2011-12-4528.
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It has been theorized that most proteins are under selection pressure to be soluble in crowded cellular spaces. To maintain solubility a proteins’ aggregation propensity should be inversely proportional to their maximum likely concentration. This theory was examined by comparing the proteome of the model organism S. cerevisiae, which has previously undergone a Whole Genome Duplication (WGD) event to the proteome of the closely related yeast K. waltii, which has not undergone WGD. This comparison revealed the following: 1) Predicted aggregation propensities are higher in S. cerevisiae than K. waltii. 2) Aggregation propensity does not predict which genes reverted to a single copy after WGD. 3) In genes which were retained as duplicates in S. cerevisiae after WGD, aggregation propensities rose from the inferred common ancestral protein. 4) Genes retained as duplicates showed less of an increase relative to their homologues in K. waltii than genes which were not retained as duplicates. 5) The relationship between the log predicted aggregation propensity and log mRNA expression level or log protein abundance was not linear as previously predicted. These results suggest that while there is broad selection pressure for reduced aggregation pressure for genes which have been duplicated, the precise relationship between aggregation propensity and gene expression is more complicated than previously predicted. These results also allow speculation that the whole genome duplication in S.cerevisiae may have been made possible by a general relaxation of aggregation-related selection pressure.<br>text
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Keller, Brigitte D. [Verfasser]. "Search for new steroid hormone metabolizing enzymes : functional genomics of the short chain dehydrogenase, reductase superfamily / Brigitte D. Keller." 2006. http://d-nb.info/985501227/34.
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Harrington, Dean J., and I. C. Sutcliffe. "Pattern searches for the identification of putative lipoprotein genes in Gram positive bacterial genomes." 2002. http://hdl.handle.net/10454/3167.
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No<br>N-terminal lipidation is a major mechanism by which bacteria can tether proteins to membranes and one which is of particular importance to Gram-positive bacteria due to the absence of a retentive outer membrane. Lipidation is directed by the presence of a cysteine-containing `lipobox' within the lipoprotein signal peptide sequence and this feature has greatly facilitated the identification of putative lipoproteins by gene sequence analysis. The properties of lipoprotein signal peptides have been described previously by the Prosite pattern PS00013. Here, a dataset of 33 experimentally verified Gram-positive bacterial lipoproteins (excluding those from Mollicutes) has been identified by an extensive literature review. The signal peptide features of these lipoproteins have been analysed to create a refined pattern, G+LPP, which is more specific for the identification of Gram-positive bacterial lipoproteins. The ability of this pattern to identify probable lipoprotein sequences is demonstrated by a search of the genome of Streptococcus pyogenes, in comparison with sequences identified using PS00013. Greater discrimination against likely false-positives was evident from the use of G+LPP compared with PS00013. These data confirm the likely abundance of lipoproteins in Gram-positive bacterial genomes, with at least 25 probable lipoproteins identified in S. pyogenes
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Hertel, Jana, Jong Danielle de, Manja Marz, Dominic Rose, Hakim Tafer, Andrea Tanzer, Bernd Schierwater, and Peter F. Stadler. "Non-coding RNA annotation of the genome of Trichoplax adhaerens." 2009. https://ul.qucosa.de/id/qucosa%3A32946.
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A detailed annotation of non-protein coding RNAs is typically missing in initial releases of newly sequenced genomes. Here we report on a comprehensive ncRNA annotation of the genome of Trichoplax adhaerens, the presumably most basal metazoan whose genome has been published to-date. Since blast identified only a small fraction of the best-conserved ncRNAs—in particular rRNAs, tRNAs and some snRNAs—we developed a semi-global dynamic programming tool, GotohScan, to increase the sensitivity of the homology search. It successfully identified the full complement of major and minor spliceosomal snRNAs, the genes for RNase P and MRP RNAs, the SRP RNA, as well as several small nucleolar RNAs. We did not find any microRNA candidates homologous to known eumetazoan sequences. Interestingly, most ncRNAs, including the pol-III transcripts, appear as single-copy genes or with very small copy numbers in the Trichoplax genome.