Dissertations / Theses: 'Genomics and transcriptomics'

1

Burnham, Katie. "Functional genomics of the sepsis response." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:cb98af40-1b66-4966-a643-ae8dfec2c122.

Full text

Abstract:

Sepsis is defined as a dysregulated immune response to infection causing organ dysfunction, and is a major area of unmet clinical need. Although conventionally considered a unified disease with a common pathway to organ failure and death, substantial clinical and molecular heterogeneity is seen, which has limited efforts to understand pathophysiology and improve therapeutic strategies. Sepsis is associated with global changes in gene expression, and genetic variants are known to affect the response to infection. This thesis therefore uses an integrated functional genomics approach to investigate disease mechanisms and variation in the sepsis response. Data are presented for 551 patients admitted to intensive care with sepsis due to community acquired pneumonia (CAP) or faecal peritonitis (FP). The sepsis response is explored using genome-wide gene expression and proteomics data, and molecular quantitative trait loci (QTL) are mapped in the context of disease. Comparisons with cardiac surgery patients are performed to identify shared and specific aspects of the host response. The host transcriptomic response was largely shared across sources of sepsis, although some specificity relating to viral infection and interferon signalling was observed and validated in prospectively recruited patients. Expression-based sepsis response signature (SRS) subgroups previously described in CAP were validated, and were additionally observed in FP. SRS1 is associated with higher early mortality, and shows enrichment of pathways relating to T cell exhaustion, cell death, and endotoxin tolerance. Differences between SRS groups were also observed in the FP plasma proteome. Serial sampling enabled the investigation of temporal changes in gene expression and protein abundance within patients. Lastly, disease-relevant expression QTL were identified, and interactions with source of sepsis and SRS determined, highlighting the potential impact of regulatory variation on the sepsis response. This thesis demonstrates the benefit of an integrative functional genomics approach to explore heterogeneity in sepsis, and highlights opportunities for patient stratification and personalised medicine.

APA, Harvard, Vancouver, ISO, and other styles

2

Krishnan, Vandhana. "Computational approaches for comparative genomics and transcriptomics using 454 sequencing technology." Pullman, Wash. : Washington State University, 2009. http://www.dissertations.wsu.edu/Thesis/Summer2009/v_krishnan_072409.pdf.

Full text

Abstract:

Thesis (M.S. in computer science)--Washington State University, August 2009.
Title from PDF title page (viewed on Aug. 12, 2009). "School of Electrical Engineering and Computer Science." Includes bibliographical references (p. 80-87).

APA, Harvard, Vancouver, ISO, and other styles

3

Jiang, Xiaofang. "Genomics and Transcriptomics Analysis of the Asian Malaria Mosquito Anopheles stephensi." Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/79959.

Full text

Abstract:

Anopheles stephensi is a potent vector of malaria throughout the Indian subcontinent and Middle East. An. stephensi is emerging as a model for molecular and genetic studies of mosquito-parasite interactions. Here we conducted a series of genomic and transcriptomic studies to improve the understanding of the biology of Anopheles stephensi and mosquito in general. First we reported the genome sequence and annotation of the Indian strain of the type form of An. stephensi. The 221 Mb genome assembly was produced using a combination of 454, Illumina, and PacBio sequencing. This hybrid assembly method was significantly better than assemblies generated from a single data source. A total of 11,789 protein-encoding genes were annotated using a combination of homology and de novo prediction. Secondly, we demonstrated the presence of complete dosage compensation in An. stephensi by determining that autosomal and X-linked genes have very similar levels of expression in both males and females. The uniformity of average expression levels of autosomal and X-linked genes remained when An. stephensi gene expression was normalized by that of their Ae. aegypti orthologs, strengthening the conclusion of complete dosage compensation in Anopheles. Lastly, we investigated trans-splicing events in Anopheles stephensi. We identified six trans-splicing events and all the trans-splicing sites are conserved and present in Ae. aegypti. The proteins encoded by the trans-spliced mRNAs are also highly conserved and their orthologs are co-linearly transcribed in out-groups of family Culicidae. This finding indicates the need to preserve the intact mRNA and protein function of the broken-up genes by trans-splicing during evolution. In summary, we presented the first genome assembly of Anopheles stephensi and studied two interesting evolution events" dosage compensation and trans-splicing - via transcriptomic analysis.
Ph. D.

APA, Harvard, Vancouver, ISO, and other styles

4

Ghobakhlou, Abdollah. "Genomics, Transcriptomics and Metabolomics of cold adaptation in arctic Mesorhizobium sp. N33." Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/29489/29489.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Lee, Kevin Joseph. "Transcriptomics of malaria host-pathogen interactions in primates." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/54264.

Full text

Abstract:

Malaria is a pernicious disease that has greatly impacted and continues to affect the human population. While much research has been performed to understand the underlying nature of this disease, gaps in the knowledge-base persist. In order to address these deficiencies, a multi-disciplinary, multi-institutional project has been funded to study the systems biology of the host pathogen interaction during malaria infection in both humans and non-human primates. In the course of investigating the transcriptome during two 100-day experiments in Macaca mulatta, this work elucidated many of the underlying molecular pathways of the host and parasite that are affected by antimalarial drugs, as well as through host-pathogen interactions. The malaria-disease-related host pathways are related to, not surprisingly, immune-associated signalling and hematopoesis, and the altered parasite pathways demonstrate an association between disease severity and parasite life stage abundance. Continuing integration of this research with other data-types collected during the course of these experiments will improve our understanding of malaria systems biology and improve targeted malaria therapies.

APA, Harvard, Vancouver, ISO, and other styles

6

Bohnert, Regina [Verfasser], and Gunnar [Akademischer Betreuer] Rätsch. "Computational Methods for High-Throughput Genomics and Transcriptomics / Regina Bohnert ; Betreuer: Gunnar Rätsch." Tübingen : Universitätsbibliothek Tübingen, 2011. http://d-nb.info/1162699280/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

Nelson, A. D. L., E. S. Forsythe, U. K. Devisetty, D. S. Clausen, A. K. Haug-Batzell, A. M. R. Meldrum, M. R. Frank, E. Lyons, and M. A. Beilstein. "A Genomic Analysis of Factors Driving lincRNA Diversification: Lessons from Plants." GENETICS SOCIETY AMERICA, 2016. http://hdl.handle.net/10150/621708.

Full text

Abstract:

Transcriptomic analyses from across eukaryotes indicate that most of the genome is transcribed at some point in the developmental trajectory of an organism. One class of these transcripts is termed long intergenic noncoding RNAs (lincRNAs). Recently, attention has focused on understanding the evolutionary dynamics of lincRNAs, particularly their conservation within genomes. Here, we take a comparative genomic and phylogenetic approach to uncover factors influencing lincRNA emergence and persistence in the plant family Brassicaceae, to which Arabidopsis thaliana belongs. We searched 10 genomes across the family for evidence of >5000 lincRNA loci from A. thaliana. From loci conserved in the genomes of multiple species, we built alignments and inferred phylogeny. We then used gene tree/species tree reconciliation to examine the duplication history and timing of emergence of these loci. Emergence of lincRNA loci appears to be linked to local duplication events, but, surprisingly, not whole genome duplication events (WGD), or transposable elements. Interestingly, WGD events are associated with the loss of loci for species having undergone relatively recent polyploidy. Lastly, we identify 1180 loci of the 6480 previously annotated A. thaliana lincRNAs (18%) with elevated levels of conservation. These conserved lincRNAs show higher expression, and are enriched for stress-responsiveness and cis-regulatory motifs known as conserved noncoding sequences (CNSs). These data highlight potential functional pathways and suggest that CNSs may regulate neighboring genes at both the genomic and transcriptomic level. In sum, we provide insight into processes that may influence lincRNA diversification by providing an evolutionary context for previously annotated lincRNAs.

APA, Harvard, Vancouver, ISO, and other styles

8

Hearn, Jack. "Exploring population history and gall induction in cynipid gall wasps using genomics and transcriptomics." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/8925.

Full text

Abstract:

Cynipid gall wasps have fascinating biology that has piqued the interest of naturalists throughout history. They induce morphologically complex, sometimes spectacular, gall structures on plants in which the larval stages develop. Gall wasps have therefore evolved an intimate association with their hosts - both metabolically, and in terms of their population histories. Gall wasps must both interact physiologically with their hosts to induce galls, and track their host plants through space and time. My thesis centres on two uses of genomic data in understanding the biology of the oak apple gall wasp Biorhiza pallida. I provide a comprehensive investigation into patterns of oak and gall wasp gene expression associated with gall induction, and a population genomic reconstruction of the population history of this species across the Western Palaearctic. While advances in sequencing technology and reduced costs have made these aims possible, analysis of the massive resulting datasets generated creates new challenges. Firstly, in reconstructing the population history of B. pallida, I describe the use of shotgun sequencing and an informatic pipeline to generate alignments of several thousand loci for three B. pallida individuals sampled from putative glacial refugia across the Western Palaearctic in Iberia, the Balkans and Iran. This dataset was analysed using a new maximum likelihood method capable of estimating population splitting and admixture among refugia across very large numbers of loci. The results showed an ancient divide between Iberia and the other two refugia, followed by very recent admixture between easternmost and westernmost regions. This suggests that gall wasps have migrated westwards along the North African coast as well as through mainland Europe. Second, I compare the gene expression profiles of gall wasp and oak tissues sampled from each of three stages of gall development, leading to new insights into potential mechanisms of gall wasp-oak interaction. A highly expressed gall wasp protein was identified that is hypothesised to stimulate somatic embryogenesis-like development of the gall through interaction with oak tissue glycoproteins. Highly expressed oak genes include those coding for nodulin-like proteins similar to those involved in legume nodule formation. Finally, analysis of the gall wasp genome has revealed potential, but as yet unconfirmed, horizontal gene transfer events into gall wasp genomes. Genes discovered in three gall wasp genomes and expressed in three transcriptomes encode plant cell wall degrading enzymes. They are not of hymenopteran origin, and are most homologous to genes of plant pathogenic bacteria. These genes could be involved in several aspects of gall wasp biology, including feeding and developmental manipulation of host plant tissue.

APA, Harvard, Vancouver, ISO, and other styles

9

Cortes, Bermudez Diego Fernando. "Functional genomics through metabolite profiling and gene expression analysis in Arabidopsis thaliana." Diss., Virginia Tech, 2008. http://hdl.handle.net/10919/28457.

Full text

Abstract:

In the post-genomic era, one of the most important goals for the community of plant biologists is to take full advantage of the knowledge generated by the Arabidopsis thaliana genome project, and to employ state-of-the-art functional genomics techniques to assign function to each gene. This will be achieved through a complete understanding of what all cellular components do, and how they interact with one another to produce a phenotype. Among the proteins encoded by the Arabidopsis genome are 24 related carboxyl methyltransferases that belong to the SABATH family. Several of the SABATH methyltransferases convert plant hormones, like jasmonic acid, indole-3-acetic acid, salicylic acid, gibberellins, and other plant constituents into methyl esters, thereby regulating the biological activity of these molecules and, consequently, myriad important physiological processes. Our research aims to decipher the function of proteins belonging to the SABATH family by applying a combination of genomics tools, including genome-wide expression analysis and gas-chromatography coupled with mass spectrometry-based metabolite profiling. Our results, combined with available biochemical information, provide a better understanding of the physiological role of SABATH methyltransferases, further insights into secondary plant metabolism and deeper knowledge of the consequences of modulating the expression of SABATH methyltransferases, both at the genome-wide expression and metabolite levels.
Ph. D.

APA, Harvard, Vancouver, ISO, and other styles

10

Xue, Xia. "Genomics and Transcriptomics of Antarctic Nematodes Reveal Drivers of Life History Evolution and Genome Evolution." BYU ScholarsArchive, 2018. https://scholarsarchive.byu.edu/etd/7422.

Full text

Abstract:

Elemental stoichiometry defines a critical understanding of the relationship between nutrient availability and usage throughout different levels of the biological community. We found there is a link between available phosphorus (P), cellular phosphorus, and nematode development as postulated by the growth rate hypothesis (GRH). I predicted that in a P-poor environment, cellular RNA concentrations would be lower than they are in P-rich environment, and thus the 18s rRNA expression level will have reduced. To most efficiently regulate the uptake of limited P, I predicted that nematodes in P-poor environments would decrease the number of copies of the 18s rRNA gene in their genome. I measured life history traits as well as rRNA gene expression and gene copy number. We found that elemental stoichiometry predicts evolutionary changes consistent with the Growth Rate Hypothesis. We sequenced and assembled a draft genome of P. murrayi. Although we expected to find genes responsible for stress tolerance, we hypothesized that in response to strong selection pressure associated with living in a simplified ecosystem, over time the genome of P. murrayi should have undergone significant decay (gene loss) relative to species in ecosystems structured more strongly by biotic interactions. We found significantly fewer genes in P. murrayi. To compare patterns of gene expression between two highly divergent Antarctic nematode species, we sequenced and assembled the transcriptomes of S. lindsayae and P. murrayi. Under laboratory conditions at 4˚C, S. lindsayae had significantly lower rates of gene expression but expressed a significantly larger number of genes. We speculate that the differences in gene expression are correlated with life history traits (developmental rates) while the differences in the number of genes expressed can be explained by their different genetic systems (S. lindsayae is amphimictic, P. murrayi is parthenogenic) and the soil environments to which they are adapted. Since we previously showed that differences in available P content can influence the evolution of gene expression via gene copy number, and that this ultimately influences growth rate, we wondered how much of this response is driven by genetics versus how strongly these patterns are driven by temperature. To better understand this, we maintained wild type populations of P. murrayi in P-rich and P-poor conditions at 5˚C, 10˚C and 15˚C in the laboratory for over 40 generations and sequenced the transcriptomes prepared from each treatment group. We found that nutrient levels played an important role in gene expression when the temperature is optimal for P. murrayi culturing and that temperature is more important in gene expression when the available P is limited. This work underscores the utility of using principles of elemental stoichiometry coupled with genomic and transcriptomics research tools to make and test predictions about life history evolution. The results of my work also inform inferences about the ways in which nutrient availability also drives the organization of trophic interactions and ultimately ecosystems.

APA, Harvard, Vancouver, ISO, and other styles

11

Vijay, Nagarjun. "Speciation genomics : A perspective from vertebrate systems." Doctoral thesis, Uppsala universitet, Evolutionsbiologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-265342.

Full text

Abstract:

Species are vital entities in biology. Species are generally considered to be discrete entities, consisting of a group of (usually interbreeding) individuals that are similar in phenotype and genetic composition, yet differ in significant ways from other species. The study of speciation has focussed on understanding general evolutionary mechanisms involved in the accumulation of differences both at the genetic and phenotypic level. In this thesis, I investigate incipient speciation, an early stage of divergence towards evolutionary independence in closely related natural populations. I make ample use of recent advances in sequencing technology that allow 1) characterizing phenotypic divergence at the level of the transcriptome and 2) delineate patterns of genetic variation at genome-scale from which processes are inferred by using principles of population genetic theory. In the first paper, we assembled a draft genome of the hooded crow and investigated population differentiation across a famous European hybrid zone. Comparing sequence differentiation peaks between and within the colour morphs, we could identify regions of the genome that show differentiation only between colour morphs and that could be related to gene expression profiles of the melanogenesis pathway coding for colour differences. The second paper expands on the first paper in that it includes crow population samples from across the entire Palaearctic distribution spanning two additional zones of contact between colour morphs. The results suggest that regions associated with selection against gene flow between colour morphs were largely idiosyncratic to each contact zone and emerged against a background of conserved 'islands of differentiation' due to shared linked selection. The third paper focusses on five killer whale ecotypes with distinct feeding and habitat specific adaptations. Differing levels of sequence differentiation between these ecotypes places them along a speciation continuum and provides a unique temporal cross-section of the speciation process. Using genome scans we identified regions of the genome that show ecotype specific differentiation patterns which might contain candidate genes involved in adaptation. In the fourth and final paper, I assumed a comparative genomic perspective to the problem of heterogeneous genomic differentiation during population divergence. The relatively high correlations in the diversity landscapes as well as differentiation patterns between crow, flycatcher and Darwin's Finch populations is best explained by conservation in broad-scale recombination rate and/or association with telomeres and centromeres conducive to shared, linked selection.

APA, Harvard, Vancouver, ISO, and other styles

12

Nelson, Andrew D. L., Upendra K. Devisetty, Kyle Palos, Asher K. Haug-Baltzell, Eric Lyons, and Mark A. Beilstein. "Evolinc: A Tool for the Identification and Evolutionary Comparison of Long Intergenic Non-coding RNAs." FRONTIERS MEDIA SA, 2017. http://hdl.handle.net/10150/624658.

Full text

Abstract:

Long intergenic non-coding RNAs (lincRNAs) are an abundant and functionally diverse class of eukaryotic transcripts. Reported lincRNA repertoires in mammals vary, but are commonly in the thousands to tens of thousands of transcripts, covering similar to 90% of the genome. In addition to elucidating function, there is particular interest in understanding the origin and evolution of lincRNAs. Aside from mammals, lincRNA populations have been sparsely sampled, precluding evolutionary analyses focused on their emergence and persistence. Here we present Evolinc, a two-module pipeline designed to facilitate lincRNA discovery and characterize aspects of lincRNA evolution. The first module (Evolinc-I) is a lincRNA identification workflow that also facilitates downstream differential expression analysis and genome browser visualization of identified lincRNAs. The second module (Evolinc-II) is a genomic and transcriptomic comparative analysis workflow that determines the phylogenetic depth to which a lincRNA locus is conserved within a user-defined group of related species. Here we validate lincRNA catalogs generated with Evolinc-I against previously annotated Arabidopsis and human lincRNA data. Evolinc-I recapitulated earlier findings and uncovered an additional 70 Arabidopsis and 43 human lincRNAs. We demonstrate the usefulness of Evolinc-II by examining the evolutionary histories of a public dataset of 5,361 Arabidopsis lincRNAs. We used Evolinc-II to winnow this dataset to 40 lincRNAs conserved across species in Brassicaceae. Finally, we show how Evolinc-II can be used to recover the evolutionary history of a known lincRNA, the human telomerase RNA (TERC). These latter analyses revealed unexpected duplication events as well as the loss and subsequent acquisition of a novel TERC locus in the lineage leading to mice and rats. The Evolinc pipeline is currently integrated in CyVerse's Discovery Environment and is free for use by researchers.

APA, Harvard, Vancouver, ISO, and other styles

13

Gerrard, Diana Lea. "Characterization Of Epigenetic Plasticity And Chromatin Dynamics In Cancer Cell Models." ScholarWorks @ UVM, 2019. https://scholarworks.uvm.edu/graddis/1060.

Full text

Abstract:

Cancer progression is driven by cumulative changes that promote and maintain the malignant phenotype. Epigenetic alterations are central to malignant transformation and to the development of therapy resistance. Changes in DNA methylation, histone acetylation and methylation, noncoding RNA expression and higher-order chromatin structures are epigenetic features of cancer, which are independent of changes in the DNA sequence. Despite the knowledge that these epigenetic alterations disrupt essential pathways that protect cells from uncontrolled growth, how these modifications collectively coordinate cancer gene expression programs remains poorly understood. In this dissertation, I utilize molecular and informatic approaches to define and characterize the genome-wide epigenetic patterns of two important human cancer cell models. I further explore the dynamic alterations of chromatin structure and its interplay with gene regulation in response to therapeutic agents. In the first part of this dissertation, pancreatic ductal adenocarcinoma (PDAC) cell models were used to characterize genome-wide patterns of chromatin structure. The effects of histone acetyltransferase (HAT) inhibitors on chromatin structure patterns were investigated to understand how these potential therapeutics influence the epigenome and gene regulation. Accordingly, HAT inhibitors globally target histone modifications and also impacted specific gene pathways and regulatory domains such as super-enhancers. Overall, the results from this study uncover potential roles for specific epigenomic domains in PDAC cells and demonstrate epigenomic plasticity to HAT inhibitors. In the second part of this dissertation, I investigate the dynamic changes of chromatin structure in response to estrogen signaling over a time-course using Estrogen Receptor (ER) positive breast cancer cell models. Accordingly, I generated genome-wide chromatin contact maps, ER, CTCF and regulatory histone modification profiles and compared and integrated these profiles to determine the temporal patterns of regulatory chromatin compartments. The results reveal that the majority of alterations occur in regions that correspond to active chromatin states, and that dynamic chromatin is linked to genes associated with specific cancer growth and metabolic signaling pathways. To distinguish ER-regulated processes in tamoxifen-sensitive and in tamoxifen-resistant (TAMR) cell models, we determined the corresponding chromatin and gene expression profiles using ER-positive TAMR cancer cell derivatives. Comparison of the patterns revealed characteristic features of estrogen responsiveness and show a global reprogramming of chromatin structure in breast cancer cells with acquired tamoxifen resistance. Taken together, this dissertation reveals novel insight into dynamic epigenomic alterations that occur with extrinsic stimuli and provides insight into mechanisms underlying the therapeutic responses in cancer cells.

APA, Harvard, Vancouver, ISO, and other styles

14

Lahrmann, Urs [Verfasser], and Alga [Akademischer Betreuer] Zuccaro. "Genomics and Transcriptomics of the sebacinoid fungi Piriformospora indica and Sebacina vermifera / Urs Lahrmann. Betreuer: Alga Zuccaro." Marburg : Philipps-Universität Marburg, 2014. http://d-nb.info/1051934826/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Gibbons, Justin Allan. "Genomics and Transcriptomics Approaches to Understanding Drug Resistance Mechanisms in the Malaria Parasite Plasmodium falciparum." Scholar Commons, 2019. https://scholarcommons.usf.edu/etd/7794.

Full text

Abstract:

The malaria parasite Plasmodium falciparum is responsible for about 500,000 deaths a year and is evolving resistance to the front-line treatment of artemisinin-based combination therapy. Resistance is currently confined to South East Asia, however millions of lives will be at risk if resistance spreads to Africa. Understanding the mechanism of resistance to artemisinins would aid containment strategies to prevent the spread of artemisinin resistance. There is also an urgent need to accelerate drug discovery since drug resistance has already been documented to all existing antimalarials. Here, I report on our efforts to understand the function of the gene k13, the gene with the strongest association with artemisinin resistance, and the potential genetic mechanisms associated with resistance to atovaquone, another widely used antimalarial. To precisely study the transcriptome characteristics of an isogenic k13 dysregulation mutant and wild type strain, I developed a new computational algorithm called Dephasing Identifier (DI) that is capable of identifying the genes dysregulated in cell cycle shifts. DI is designed to solve the problem of pinpointing important patterns in complex genomics data with temporal sequences that cannot be resolved by standard pair-wise comparison methods, by using an innovative method that leverages external reference data for systematic comparisons. In the k13 study, I demonstrated that the algorithm identifies co- regulated gene sets that have consistent annotated functions. The DI algorithm successfully identified aberrantly early DNA replication as the driving process of transcriptome changes in the mutant. To understand genome-wide changes that occurred in a set of atovaquone resistance stains, I analyzed whole genome sequencing data previously generated for a P. falciparum strain that underwent in vitro atovaquone selection to create atovaquone resistant strains. I systematically analyzed the genomes of these strains to search for significant genetic changes associated with atovaquone resistance; and used stringent criteria to identify genes involved in regulating transcription and protein modifications as acquiring non- synonymous mutations. Additionally, copy number variations in plasmepsin genes, a family known to be involved in resistance, were found in the resistant strains. In summary, genomics and transcriptomics technologies can be used to rapidly identify resistance mechanisms allowing for faster adjustment of current containment strategies. Future research on the critical targets identified in this study can aid new drug discovery efforts and novel control strategies.

APA, Harvard, Vancouver, ISO, and other styles

16

LAMONTANARA, ANTONELLA. "Sviluppo ed applicazione di pipilines bioinformatiche per l'analisi di dati NGS." Doctoral thesis, Università Cattolica del Sacro Cuore, 2015. http://hdl.handle.net/10280/6068.

Full text

Abstract:

Lo sviluppo delle tecnologie di sequenziamento ha portato alla nascita di strumenti in grado di produrre gigabasi di dati di sequenziamento in una singola corsa. Queste tecnologie, comunemente indicate come Next Generation Sequencing o NGS, producono grandi e complessi dataset la cui analisi comporta diversi problemi a livello bioinformatico. L'analisi di questo tipo di dati richiede la messa a punto di pipelines computazionali il cui sviluppo richiede un lavoro di scripting necessario per concatenare i softwares già esistenti. Questa tesi tratta l'aspetto metodologico dell'analisi di dati NGS ottenuti con tecnologia Illumina. In particolare in essa sono state sviluppate tre pipelines bioinformatiche applicate ai seguenti casi studio: 1) uno studio di espressione genica mediante RNA-seq in "Olea europaea" finalizzato all’indagine dei meccanismi molecolari alla base dell’acclimatazione al freddo in questa specie; 2) uno studio mediante RNA-seq finalizzato all’identificazione dei polimorfismi di sequenza nel trascrittoma di due razze bovine mirato a produrre un ampio catalogo di marcatori di tipo SNPs; 3) il sequenziamento, l’assemblaggio e l’annotazione del genoma di un ceppo di Lactobacillus plantarum che mostrava potenziali proprietà probiotiche.
The advance in sequencing technologies has led to the birth of sequencing platforms able to produce gigabases of sequencing data in a single run. These technologies commonly referred to as Next Generation Sequencing or NGS produce millions of short sequences called “reads” generating large and complex datasets that pose several challenges for Bioinformatics. The analysis of large omics dataset require the development of bioinformatics pipelines that are the organization of the bioinformatics tools in computational chains in which the output of one analysis is the input of the subsequent analysis. A work of scripting is needed to chain together a group of existing software tools.This thesis deals with the methodological aspect of the data analysis in NGS sequencing performed with the Illumina technology. In this thesis three bioinformatics pipelines were developed.to the following cases of study: 1) a global transcriptome profiling of “Oleaeuropeae” during cold acclimation, aimed to unravel the molecular mechanisms of cold acclimation in this species; 2) a SNPs profiling in the transcriptome of two cattle breeds aimed to produce an extensive catalogue of SNPs; 3) the genome sequencing, the assembly and annotation of the genome of a Lactobacillus plantarum strain showing probiotic properties.

APA, Harvard, Vancouver, ISO, and other styles

17

Domènech, Salgado Laura 1989. "A Comprehensive multiomics approach towards understanding obsessive-compulsive disorder." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/665800.

Full text

Abstract:

To date, very little progress has been made towards elucidating the genetic causes of obsessive-compulsive disorder (OCD). In this project we have performed rare variant association study (RVAS) transcriptomics and metagenomics analyses to focus on areas relatively underexplored in OCD. We have identified and replicated an enrichment of rare variants in TMEM63A, a gene that encodes for a calcium-permeable cation channel, through whole-exome sequencing, RVAS and targeted resequencing analyses. Moreover, we have observed an overrepresentation of genes enriched in rare variants in OCD cases related to calcium signalling. Transcriptomic studies have identified differential expression of genes involved in neuronal development and function in OCD patients. Integration of our RVAS and transcriptomic results also uncover a possible role of semaphorins and axon guidance in OCD. Finally, metagenomics studies have confirmed the previously reported increase of the Rikenellaceae bacterial family in the gut microbiome and have shown a significant higher Actinobacteria/Fusobacteria ratio in the oro-pharyngeal microbiome of OCD cases. Our results actively encourage further research in these areas.
Fins a dia d’avui, s’ha avançat molt poc a l’hora d’elucidar les causes genètiques del trastorn obsessiu compulsiu (TOC). En aquest projecte hem realitzat estudis d’associació de variants rares (RVAS) i anàlisis de transcriptòmica i metagenòmica per centrar-nos en àrees relativament poc explorades del TOC. Hem identificat i replicat un enriquiment de variants rares a TMEM63A, un gen que codifica un canal catiònic permeable per calci, a través d’anàlisis de seqüenciació de l’exoma complet, RVAS i reseqüenciació dirigida. A més, hem observat una sobrerepresentació de gens enriquits en variants rares en casos de TOC relacionats amb la senyalització de calci. Els estudis de transcriptòmica han identificat una expressió diferencial de gens involucrats en el desenvolupament i la funció neuronal en els pacients de TOC. La integració dels resultats dels nostres estudis de RVAS i transcriptòmica també revelen un possible paper de les semaforines i del guiatge axonal al TOC. Finalment, els estudis de metagenòmica han confirmat el increment prèviament reportat de la família bacterial Rikenellaceae en el microbioma intestinal i han mostrat una relació significativa més alta d’Actinobacteris/Fusobacteris en el microbioma de l’orofaringe dels pacients de TOC. Els nostres resultats fomenten activament la recerca en aquestes àrees.

APA, Harvard, Vancouver, ISO, and other styles

18

Mercurio, Kevin Jay Belarmino. "Identifying Genes Required for Saccharomyces cerevisiae Growth in Mucin." Thesis, Université d'Ottawa / University of Ottawa, 2020. http://hdl.handle.net/10393/40546.

Full text

Abstract:

The human gut microbiome is a vast ecosystem of microorganisms that play an important role in human metabolism, immunological function, and even inflammatory gut diseases. Metagenomics research on the human gut microbiome has demonstrated the presence of DNA from dietary yeast species like Saccharomyces cerevisiae. However, it is unknown if the S. cerevisiae detected in metagenomics studies is solely from dead dietary sources or if they can live and colonize the human gut like their close relative Candida albicans. While S. cerevisiae can adapt to low oxygen and acidic environments, it has yet to be explored whether it can metabolize mucin, the primary carbon source found in the mucus layer of the human gut. Mucins are large, gel-forming, highly glycosylated proteins that make up a majority of carbohydrate sources in the gut mucosa. This work determined that S. cerevisiae can utilize mucin as their main carbon source which results in a significant reduction in cell size. Additionally, an aspartyl protease named Yps7, part of a family containing known homologues to mucin-degrading C. albicans proteins in S. cerevisiae, is important for growth on mucin media. To further identify biological pathways required to grow optimally in mucin, both a transcriptome analysis on wild type cells (BY4743) and a chemogenomics screen was performed. In total, 2131 genes demonstrated significant differential expression in mucin media, and 30 genes upon their deletion impacted their growth on mucin. Both these screens suggest that mitochondrial function is required for proper growth in mucin, which was further elucidated by the change in mitochondrial morphology and oxygen consumption in yeast cells upon mucin treatment. Indeed, the uncharacterized open reading frame YCR095W-A is required for growth on mucin as the deletion mutant showed dysfunction in mitochondrial morphology and cellular respiration, further suggesting a potential role in mitochondrial function. Importantly, this project serves as the initial step towards establishing if our most common dietary fungus can survive in the mucus environment of the human gut.

APA, Harvard, Vancouver, ISO, and other styles

19

Hanson, Sara Jeanette. "The molecular evolution of reproduction in animals: insights from sexual and asexual rotifers." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/1618.

Full text

Abstract:

Sex and meiosis are ubiquitous in eukaryotes as the primary mode of reproduction. This suggests that despite the theoretical energetic advantages of asexual reproduction, organisms capable of sexual reproduction are at a much greater long-term evolutionary advantage. Rotifers, a group of microinvertebrates, offer unique opportunities to examine the evolution of sex due to their extensive proliferation, successful adaptation to a wide variety of ecological niches, and the diversity of reproductive modes represented in the group. The cyclically parthenogenetic monogonont rotifers have overcome constraints on the loss of sexual reproduction in order to frequently transition between sexual and asexual generations, making them a powerful system with which to address the maintenance of sex in animals. Obligately asexual bdelloid rotifers appear to have thrived without sex for tens of millions of years, a period of time much longer than expected given the hypothesized advantages of sexual reproduction. However, the molecular nature of sex and parthenogenesis is poorly understood in any rotifer species. To expand our knowledge of the molecular mechanisms of monogonont reproduction, we sequenced genomes of two distantly related species, Brachionus calyciflorus and Brachionus manjavacas and identified over 80 homologs for genes involved in meiotic processes. Several of these genes have undergone duplication events specific to the monogonont lineage, including genes with known roles in regulation of cell cycle transitions during meiosis. In addition, global gene expression patterns were determined using obligate parthenogenetic (OP) and cyclical parthenogenetic (CP) strains of B. calyciflorus. Quantitative comparison of expression between these strains revealed differentially expressed genes specific to sexual and asexual reproduction in this species, including genes related to dormancy/resting egg formation, meiosis, and hormone signaling pathways that are thought to be involved in the induction of sexual reproduction in monogononts. Finally, we analyzed gene expression in bdelloid rotifers for evidence of sexual reproduction or the utilization of meiotic genes under conditions inducing high levels of recombination. Through this work, we have established molecular markers for sexuality and asexuality in monogonont rotifers, and used these markers to evaluate reproduction in bdelloids. The data generated specifically allows for more informed analyses of the evolution of cyclical parthenogenesis and rotifer reproduction. Furthermore, this work extends the use of monogononts as a model system for addressing broader questions regarding the evolution of sexual reproduction.

APA, Harvard, Vancouver, ISO, and other styles

20

Huang, Yun [Verfasser]. "Combining genomics and transcriptomics to study adaptation to lake and river habitats in three-spined sticklebacks / Yun Huang." Kiel : Universitätsbibliothek Kiel, 2018. http://d-nb.info/1152264176/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Lachance, Hannah. "Cisco Science: Using Omics To Answer A Range Of Key Questions." ScholarWorks @ UVM, 2019. https://scholarworks.uvm.edu/graddis/1135.

Full text

Abstract:

Coregonines, including cisco (Coregonus artedi), kiyi (Coregonus kiyi), and bloater (Coregonus hoyi), are a focus for prey fish conservation and restoration efforts throughout the Laurentian Great Lakes. However, fundamental questions about coregonine ecology and genetics remain. For example, we know little about how the early life stages of coregonines respond to environmental change at either the genotypic or phenotypic level. We also have limited knowledge about how to identify different species at the larval stage and the genetic relationships among species, which makes the different species difficult to study at the larval stage. To increase the probability for success in restoration efforts, current and future research need to integrate traditional and novel approaches to better understand what leads to current and future coregonine successes. We used DNA and RNA omics tools, genomics and transcriptomics to boost our comprehension of current coregonine populations and to help understand how C. artedi may respond to environmental change. During the winter of 2017, we conducted a pilot experiment to evaluate how C. artedi eggs may respond to increased light exposure resulting from current and expected reductions in annual ice and snow cover due to global warming. We used transcriptomics to assess differences in gene expression between a continuous light and continuous dark treatment. Our results indicate that light is an environmental factor that could lead to earlier hatch dates, smaller yolk sacs, changes in mortality and differential gene expression in metabolic related and other functionally important genes. In 2018, we sampled larval coregonines in the Apostle Islands of Lake Superior each week from hatch in May until late July. We used genomic sequencing to genetically identify 197 larvae to species: C. artedi, C. hoyi, and C. kiyi. The larval demographic characteristics of each species was assessed and revealed that length ranges, growth rates, yolk sac condition, and effective population size varied among species. Larvae of all three species were found throughout the entirety of the Apostle Islands and the genetic diversity within each species appears high. The results from our pilot experiment and field observations help advance our understanding of the important early life stages of coregonines and how changes in light exposure or growth rates could affect their success or failure in a changing climate.

APA, Harvard, Vancouver, ISO, and other styles

22

Chai, Hui Hui. "Developing new approaches for transcriptomics and genomics : using major resources developed in model species for research in crop species." Thesis, University of Nottingham, 2014. http://eprints.nottingham.ac.uk/14246/.

Full text

Abstract:

With the estimated increase in global demand for food and over-reliance on staple food crops, the exploitation of agricultural biodiversity is important to address food security challenges. The aim of this study is to develop approaches to transfer major informational and physical resources developed in model plant and major crop species to resources poor crop species, using oil palm and Bambara groundnut as two exemplar crops. XSpecies (cross-species) approach, the core approach of the study, is described as the approach which uses microarrays developed for a given species to analyse another related species. The use of the XSpecies approach (here the cross-hybridisation of DNA from oil palm onto heterologous Affymetrix microarrays for Arabidopsis and rice), is the first experiment reported in oil palm and focused on a bulked segregant analysis of different shell-thicknesses for oil palm fruit. Primers design involved screening candidate probe-pairs filtered using PIGEONS software against oil palm transcriptome sequences generated using 454 sequencing technology. The results provided an insight into the effects of sequence divergence between oil palm and the reference species (Arabidopsis and rice) onto the power of detecting single feature polymorphism (SFPs) in oil palm, implying the importance of close association between studied and model plant/crop in XSpecies approach. The XSpecies approach coupled with genetical genomics was also tested within legumes, with Bambara groundnut as the query species compared to soybean as the resource rich species (20 Mya). A mild drought experiment, conducted in a controlled environment glasshouse, used an F5 segregating population derived from a controlled cross between DipC and Tiga Nicuru in Bambara groundnut. The cross-hybridisation of Bambara groundnut leaf RNA to the soybean GeneChip individual oligonucleotide probes resulted in a total of 1,531 of good quality gene expression markers (GEMs) on the basis of the differences in the hybridisation signal strength. The first ‘expression-based’ genetic map (GEM map) was constructed using 165 GEMs spanning 920.3 cM of Bambara groundnut genome. The first high density DNA-marker genetic map of 1,341.3 cM combining dominant DArT and co-dominant SNPs, developed using the DArT Seq approach, with additional pre-existing microarray-based DArT and SSR markers, was also developed in the F3 segregating population. Both maps were combined to form the first integrated map of 1,250.7 cM with 212 markers. Morphological differences and the rapid reduction in stomatal conductance observed within the F5 segregating population in the drought experiment provided trait data for a QTL analysis. The comprehensive QTL analysis in Bambara groundnut detected significant QTLs for morphological traits using GEM map, including internode length, peduncle length, pod number per plant, pod weight per plant, seed number per plant, seed weight per plant, 100-seed weight, shoot dry weight and harvest index across four linkage groups: LG1, LG2B, LG8B and LG11A. The loci controlling internode length and peduncle length were also consistently mapped to single marker on LG1 in DArTseq map using F3 segregating population, suggesting that these two traits are probably controlled by single gene or two closely linked genes. Despite significant genotypes effects on stomatal conductance tested in ANOVA analysis, no major QTLs were detected, suggesting the contributions of a number of small genetic effects to stomatal conductance. A preliminary homology search using the LG1 linkage group markers and associated gene models showed the ability to develop a framework for identification of candidate genes in Bambara groundnut relative to soybean. The present study also developed the resources for an eQTL analysis in a cross-species context. Translation from major and model plant species to underutilised and resource poor crops is critical to be able to develop many crop species with potential for future agriculture. This study examines some of the approaches which might be adopted and replicated in various underutilised crop species.

APA, Harvard, Vancouver, ISO, and other styles

23

Gapp, Bianca. "Functional genomics and compound mode-of-action screening in haploid human cells." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:0c2ce8f8-15f3-447f-9117-8953329bd4ac.

Full text

Abstract:

More than a decade after the completion of the human genome project, the function of a large number of genes remains to be elucidated. Forward and reverse genetic approaches have proven to be powerful tools to study gene function and have provided insights into fundamental biological processes. Furthermore, functional genetic screening can lead to a better understanding of the action of endogenous and exogenous stimuli such as hormones or drugs on biological systems. Thus far, systematic and unbiased studies have largely been limited to model organisms. However, complex disease-relevant genotypes and phenotypes cannot be studied in entirety in lower organisms creating a need for systematic approaches in human cells. This thesis describes a series of studies using forward and reverse genetic approaches combined with state-of-the-art technology in haploid human cells. The first chapter describes the development of a quantitative phenotypic read-out using a novel application of RNA-sequencing that allows the functional annotation of genes in signalling pathways. The presented data demonstrate that the employed shallow RNA-sequencing method is scalable and suitable as a read-out for reverse genetic screening. The second chapter focuses on the implementation of this method in a large reverse genetic study in human cells to functionally annotate tyrosine kinases in signalling pathways upon stimulation with a set of ten polypeptides and small molecules. The screens revealed known and unexpected interactions between different signalling molecules and pathways, validating the technical approach in a biological context. The third chapter presents a pilot study describing the set-up of a forward genetic technique for compound mode-of-action screening using a pooled human mutant cell line collection. The chemical genetic approach displayed sufficient sensitivity and allowed to monitor thousands of gene-drug interactions simultaneously. Together, this thesis combines elements to advance technological and biological aspects of functional genomics and chemical genetics.

APA, Harvard, Vancouver, ISO, and other styles

24

Cortese, Diego. "Genomic and transcriptomic sequencing in chronic lymphocytic leukemia." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-303703.

Full text

Abstract:

Identification of recurrent mutations through next-generation sequencing (NGS) has given us a deeper understanding of the molecular mechanisms involved in chronic lymphocytic leukemia (CLL) development and progression and provided novel means for risk assessment in this clinically heterogeneous disease. In paper I, we screened a population-based cohort of CLL patients (n=364) for TP53, NOTCH1, SF3B1, BIRC3 and MYD88 mutations using Sanger sequencing, and confirmed the negative prognostic impact of TP53, SF3B1 or NOTCH1 aberrations, though at lower frequencies compared to previous studies. In paper II, we assessed the feasibility of targeted NGS using a gene panel including 9 CLL-related genes in a large patient cohort (n=188). We could validate 93% (144/155) of mutations with Sanger sequencing; the remaining were at the detection limit of the latter technique, and technical replication showed a high concordance (77/82 mutations, 94%). In paper III, we performed a longitudinal study of CLL patients (n=41) relapsing after fludarabine, cyclophosphamide and rituximab (FCR) therapy using whole-exome sequencing. In addition to known poor-prognostic mutations (NOTCH1, TP53, ATM, SF3B1, BIRC3, and NFKBIE), we detected mutations in a ribosomal gene, RPS15, in almost 20% of cases (8/41). In extended patient series, RPS15-mutant cases had a poor survival similar to patients with NOTCH1, SF3B1, or 11q aberrations. In vitro studies revealed that RPS15mut cases displayed reduced p53 stabilization compared to cases wildtype for RPS15. In paper IV, we performed RNA-sequencing in CLL patients (n=50) assigned to 3 clinically and biologically distinct subsets carrying stereotyped B-cell receptors (i.e. subsets #1, #2 and #4) and revealed unique gene expression profiles for each subset. Analysis of SF3B1-mutated versus wildtype subset #2 patients revealed a large number of splice variants (n=187) in genes involved in chromatin remodeling and ribosome biogenesis. Taken together, this thesis confirms the prognostic impact of recurrent mutations and provides data supporting implementation of targeted NGS in clinical routine practice. Moreover, we provide evidence for the involvement of novel players, such as RPS15, in disease progression and present transcriptome data highlighting the potential of global approaches for the identification of molecular mechanisms contributing to CLL development within prognostically relevant subgroups.

APA, Harvard, Vancouver, ISO, and other styles

25

Chenevert, Madeline M. "A Transcriptomic Exploration of Hawaiian Drosophilid Development and Evolution." ScholarWorks@UNO, 2019. https://scholarworks.uno.edu/td/2687.

Full text

Abstract:

One in four known species of fruit flies inhabit the Hawaiian Islands. From a small number of colonizing flies, a wide range of species evolved, some of which managed to reverse-colonize other continental environments. In order to explore the developmental pathways, which separate the Hawaiian Drosophila proper and the Scaptomyza group that contains reverse-colonized species, the transcriptomes of two better-known species in each group, Scaptomyza anomala and Drosophila grimshawi, were analyzed to find changes in gene expression between the two groups. This study describes a novel transcriptome for S. anomala studies as well as unusual changes in gene expression in D. grimshawi relative to other species, revealing priorities of both species in early development.

APA, Harvard, Vancouver, ISO, and other styles

26

Richly, Erik. "Structural and functional genomics in semi-autonomous organelles composition and origin of proteomes of chloroplasts and mitochondria and related transcriptomics /." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969512104.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Rogl, Kimberley. "A genomics perspective of species and speciation in an Atyid shrimp (Paratya australiensis)." Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/207248/1/Kimberley_Rogl_Thesis.pdf.

Full text

Abstract:

The speciation debate in evolutionary science is long and protracted, evidenced by the multitude of concepts regarding species and speciation. Understanding the nature of species however, is of central importance in the study of biology and ecology. The purpose of this study was to investigate the genetic architecture of freshwater shrimp (Paratya australiensis) from two distinct lineages and of individuals across a known hybrid zone to gain insight into the process of speciation at the molecular level. The results of this study indicate that P. australiensis lineages sit in an advanced position along the speciation continuum, thus warranting taxonomic revision.

APA, Harvard, Vancouver, ISO, and other styles

28

Jeffery, N. "Beta cell differentiation status in Type 2 Diabetes." Thesis, University of Exeter, 2019. http://hdl.handle.net/10871/35724.

Full text

Abstract:

Type 2 Diabetes (T2D) affects over 415 million people globally and is characterised by cellular stresses including: poor glucose homeostasis, dyslipidaemia, inflammation, hypoxia and ER stress. Studies in mice have shown that exposure to these stresses influences beta cell differentiation status as well as cell survival and may explain the extent of beta cell mass loss that is seen in the disease. To date, studies of altered beta cell differentiation have largely been confined to murine models. I used the EndoC-bH1 human beta cell line, along with human pancreatic tissue sections, to better characterise this mechanism in human disease. To elucidate these mechanisms, I firstly established a humanised version of cell culture techniques for the EndoC βH1 cell model and assessed the influence on cell function. Secondly, I evaluated the effects of the diabetic microenvironment on beta cell differentiation and gene expression patterns. Finally, I investigated whether a diabetomimetic microenvironment induced differences in microRNA regulation in the cells. I found that the humanised EndoC-βH1 culture techniques improved glucose sensitive insulin release in the cell model. EndoC-βH1 cells exposed to a Diabetic microenvironment showed some degree of transdifferentiation and this may be due to dysregulation of splicing factor expression. These effects may be compounded by altered microRNA regulation in response to these cell stresses. These data suggest that altered gene regulation caused by a diabetic microenvironment may alter gene regulation to produce a reversible delta-like phenotype in human beta cells.

APA, Harvard, Vancouver, ISO, and other styles

29

Lebreton, Annie. "Caractéristiques génomiques du genre fongique Mucor et évolution adaptative liée à différents modes et conditions de vie au sein du genre." Thesis, Brest, 2018. http://www.theses.fr/2018BRES0098/document.

Full text

Abstract:

Le genre Mucor appartient au phylum des Mucoromycota, un groupe issu de l’une des lignées ayant divergé très tôt dans l'évolution des espèces fongiques (early diverging lineages). Ces groupes restent encore très peu connus par rapport aux Ascomycètes et Basidiomycètes. Le genre Mucor est un genre d'espèces saprophytes, avec cependant une certaine diversité au niveau du mode de vie. Il existe en effet au sein du genre, des endophytes de plantes (comme M. endophyticus) ou encore des pathogènes opportunistes d'animaux (comme les espèces thermophiles M. circinelloides ou M. indicus). Le genre est ubiquiste mais il existe des associations à certains habitats qui semblent dénoter une certaine spécialisation. L’objectif de cette thèse était de mieux connaître les potentialités génétiques du genre Mucor lui permettant ce mode de vie ubiquiste, son potentiel d'adaptation mais également de mieux comprendre l'existence au sein du genre d'espèces semblant s'être spécialisées en colonisant préférentiellement ou exclusivement certains habitats comme le fromage. Afin d'atteindre cet objectif des études transcriptomiques et génomiques comparées ont été menées dans le cadre de cette thèse, afin de déterminer les principales caractéristiques des génomes de Mucor aussi bien structurelles que fonctionnelles, identifier les similitudes au niveau des espèces étudiées et aussi leur spécificités et en fonction des modes de vie/habitats et déterminer s'il existe chez les espèces fréquemment rencontrées dans les fromages (et notamment pour celles considérées comme technologiques) des traces d'adaptation voire de domestication
The genus Mucor belongs to the phylum Mucoromycota; a group that derived from the lineages that diverged early in the evolution of fungal species (early diverging lineages). These groups have been less well studied and are less well understood in comparison to Ascomycetes and Basidiomycetes. The genus Mucor is composed of saprophytic species, but also encompasses species with diverse lifestyles.For example, it includes plant endophytes (such as M. endophyticus) or opportunistic animal pathogens (such as the thermophilic species M. circinelloides or M. indicus). The genus is ubiquitous but there are some associations with specific habitats which seem to indicate specialisation. The aim of this thesis is to better understand the genetic potential of the genus Mucor in particular, to decipher how it maintains this ubiquitous lifestyle, its capacity to adapt to diverses habitats and to better understand the existence within the genus of species that may have undergone specialization allowing them to preferentially or exclusively colonise certain habitats, such as cheese. In order to achieve this, we have performed comparative transcriptomic and genomic studies in order to determine the main structural and functional characteristics of the Mucor genomes, identify similarities among the species studied and also assess whether there exist specific genetic associations with lifestyle/habitat and determine whether the species frequently found in cheese (in particular those species considered as technological) harbour imprints of adaptation or even domestication

APA, Harvard, Vancouver, ISO, and other styles

30

Logotheti, Marianthi. "Integration of functional genomics and data mining methodologies in the study of bipolar disorder and schizophrenia." Doctoral thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-52644.

Full text

Abstract:

Bipolar disorder and schizophrenia are two severe psychiatric disorders characterized by a complex genetic basis, coupled to the influence of environmental factors. In this thesis, functional genomic analysis tools were used for the study of the underlying pathophysiology of these disorders, focusing on gene expression and function on a global scale with the application of high-throughput methods. Datasets from public databases regarding transcriptomic data of postmortem brain and skin fibroblast cells of patients with either schizophrenia or bipolar disorder were analyzed in order to identify differentially expressed genes. In addition, fibroblast cells of bipolar disorder patients obtained from the Biobank of the Neuropsychiatric Research Laboratory of Örebro University were cultured, RNA was extracted and used for microarray analysis. In order to gain deeper insight into the biological mechanisms related to the studied psychiatric disorders, the differentially expressed gene lists were subjected to pathway and target prioritization analysis, using proprietary tools developed by the group of Metabolic Engineering and Bioinformatics, of the National Hellenic Research Foundation, thus indicating various cellular processes as significantly altered. Many of the molecular processes derived from the analysis of the postmortem brain data of schizophrenia and bipolar disorder were also identified in the skin fibroblast cells. Additionally, through the use of machine learning methods, gene expression data from patients with schizophrenia were exploited for the identification of a subset of genes with discriminative ability between schizophrenia and healthy control subjects. Interestingly, a set of genes with high separating efficiency was derived from fibroblast gene expression profiling. This thesis suggests the suitability of skin fibroblasts as a reliable model for the diagnostic evaluation of psychiatric disorders and schizophrenia in particular, through the construction of promising machine-learning based classification models, exploiting gene expression data from peripheral tissues.

APA, Harvard, Vancouver, ISO, and other styles

31

Schwientek, Patrick [Verfasser]. "Genomics and transcriptomics of the industrial acarbose producer Actinoplanes sp. SE50/110 / Patrick Schwientek. Technische Fakultät. Centrum für Biotechnologie - Institut für Genomforschung und Systembiologie." Bielefeld : Universitätsbibliothek Bielefeld, Hochschulschriften, 2012. http://d-nb.info/102095454X/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Ruffing, Anne M. "Metabolic engineering and omics analysis of Agrobacterium sp. ATCC 31749 for oligosaccharide synthesis." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/39507.

Full text

Abstract:

Oligosaccharides are important biomolecules that are targets and also components of many medical treatments, including treatments for cancer, HIV, and inflammation. While the demand for medically-relevant oligosaccharides is increasing, these compounds have proven difficult to synthesize. Whole-cell oligosaccharide synthesis is a promising method that requires relatively inexpensive substrates and can complete the synthesis in just one step. However, whole-cell oligosaccharide synthesis employing common microorganisms like E. coli have been plagued by low yields. This dissertation investigates an alternative microorganism for oligosaccharide production: Agrobacterium sp. ATCC 31749. This Agrobacterium strain produces high levels of curdlan polysaccharide, demonstrating its natural ability to produce the sugar nucleotide precursor for oligosaccharide production. The two main objectives of this dissertation are 1) to develop biocatalysts for oligosaccharide synthesis by engineering ATCC 31749 and 2) to determine what factors affect poly- and oligosaccharide production in this Agrobacterium strain. ATCC 31749 was engineered to produce two oligosaccharides of medical importance: N-acetyllactosamine and galactose-α 1,3-lactose. Oligosaccharide production in the biocatalyst was further improved with additional metabolic engineering. Substrate uptake was increased through expression of a lactose permease, and availability of the sugar nucleotide substrate improved with gene knockout of the curdlan synthase gene. Both of these engineering efforts led to increased oligosaccharide synthesis in the Agrobacterium biocatalyst. Overall, the engineered Agrobacterium strains synthesized gram-scale quantities of the oligosaccharide products in just one step and requiring only a few inexpensive substrates and cofactors. Additional improvement of the oligosaccharide-producing biocatalysts required further investigation of the factors influencing poly- and oligosaccharide production in ATCC 31749. In this dissertation, several environmental and intracellular factors are identified that affect both oligosaccharide and curdlan production. Sucrose was the preferred carbon source for oligosaccharide synthesis, and the addition of citrate to the synthesis reaction led to significant improvement in oligosaccharide production. To identify the genetic factors and possible mechanisms regulating curdlan production, the genome of ATCC 31749 was sequenced. The genome sequence was utilized for transcriptome analysis of ATCC 31749. In the transcriptome analysis, genes significantly up- and down-regulated during curdlan production were identified. Subsequent gene knockout experiments showed several factors to be important for curdlan synthesis, namely the nitrogen signaling cascade, polyphosphate, and the GTP-derived second messengers (p)ppGpp and c-di-GMP. In addition to the development of biocatalysts for oligosaccharide production, this investigation provides insight into the complex mechanisms regulating exopolysaccharide synthesis.

APA, Harvard, Vancouver, ISO, and other styles

33

Pieta, Luiza. "Genômica de listeria monocytogenes e transcriptômica do microrganismo na presença de óleo essencial extraído de baccharis psiadioides." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/163557.

Full text

Abstract:

Listeria monocytogenes é um bastonete Gram-positivo, anaeróbio facultativo, psicrotrófico, patogênico a humanos e transmitido por alimentos. É causador da listeriose, doença severa que acomete grupos de risco específicos, tais como idosos, imunocomprometidos, gestantes, crianças e recém-nascidos. Neste trabalho foi investigada a expressão diferencial de L. monocytogenes na presença de óleo essencial extraído de Baccharis psiadioides, planta da família Asteraceae popularmente chamada de “alecrim-do-campo”, “vassoura” ou “erva formiga”, utilizada pela população como planta medicinal. Além disso, os genomas de dois diferentes sorotipos de L. monocytogenes, frequentemente associados a surtos de listeriose, foram sequenciados através de plataforma MiSeq Illumina, sequências estas depositadas no GenBank, e comparados com genomas de referência. Anteriormente à execução das análises genômica e transcriptômica, foi determinada a composição do óleo essencial extraído de B. psiadioides utilizado nos experimentos, através de cromatografia gasosa com espectrômetro de massa (GC – MS), a qual demonstrou uma maior quantidade de β-pineno na fração composta majoritariamente por monoterpenos, composto este frequentemente encontrado em plantas medicinais aromáticas e apontado como um dos responsáveis pelo potencial antimicrobiano das mesmas. Os demais resultados obtidos no presente trabalho indicam que o óleo essencial testado apresenta potencial ação bacteriostática na concentração estudada, sendo que genes relacionados à virulência do microrganismo foram menos transcritos na sua presença, ao contrário do que foi observado para genes de resposta ao estresse, que apresentaram maiores níveis de transcrição nesta condição. A comparação genômica entre os genomas bacterianos sequenciados neste trabalho e as cepas referência sugere um maior número de proteínas expressas em L. monocytogenes do sorotipo 4b relacionadas à defesa e metabolismo do microrganismo, indicando mecanismos que podem estar envolvidos com a capacidade deste sorotipo estar mais envolvido nos casos humanos de listeriose.
LLiisstteerriiaa mmoonnooccyyttooggeenneess is a Gram-positive rod-shaped microorganism, facultative anaerobic, psychrotrophic, pathogenic to humans and transmitted by food. It causes listeriosis, a severe disease that affects specific risk groups such as elderly, immunocompromised, pregnant women, children and newborns. In this study, differential expression of LL.. mmoonnooccyyttooggeenneess in the presence of essential oil extracted from BBaacccchhaarriiss ppssiiaaddiiooiiddeess, a plant from AAsstteerraacceeaaee family popularly named as "alecrim-do-campo", "vassoura" or "erva formiga" used by population as a medicinal plant, was investigated. In addition, the genomes of two different LL.. mmoonnooccyyttooggeenneess serotypes, often associated with listeriosis outbreaks, were sequenced through the MiSeq Illumina platform. These sequences were deposited in GenBank and compared with reference genomes. Prior to the execution of genomic and transcriptomic analyzes, composition of the essential oil extracted from BB.. ppssiiaaddiiooiiddeess used in the experiments was determined by gas chromatography with mass spectrometer (GC-MS), which demonstrated a higher amount of β-pinene in the fraction composed mainly by monoterpenes. This compound is often found in aromatic medicinal plants and also pointed as one of those responsible for their antimicrobial potential. The other results obtained in the present study indicate that the essential oil tested has a potential bacteriostatic activity at the concentration studied, and genes related to the virulence of the microorganism were less transcribed in its presence, contrary to what was observed for stress response genes, which presented higher transcription levels on that condition. Comparative genomics between the bacterial genomes sequenced in this work and the reference strains suggests a higher number of proteins expressed in LL.. mmoonnooccyyttooggeenneess serotype 4b related to the defense and metabolism of the microorganism, indicating mechanisms that may be involved with the greater ability of this serotype to cause human listeriosis.

APA, Harvard, Vancouver, ISO, and other styles

34

Lee, Bo-Hyung. "High thoughput study of biofilm and virulence in Listeria monocytogenes using innovative approaches." Thesis, Université Clermont Auvergne‎ (2017-2020), 2019. http://www.theses.fr/2019CLFAC017.

Full text

Abstract:

Listeria monocytogenes est un pathogène d'origine alimentaire à multiples facettes caractérisé par sa capacité d'adaptation dans des conditions défavorables et par sa prolifération dans une vaste gamme d'environnements, du sol aux cellules hôtes des mammifères. L'hétérogénéité génétique de L. monocytogenes se reflète dans sa structure clonale diversifiée, ce qui corrèle, dans une certaine mesure, avec des traits phénotypiques tels que la virulence ou la résistance au stress. La thèse portait sur deux phénotypes les plus éminents, la formation d'un biofilm et le potentiel de virulence, sous différents angles et à l'aide des technologies les plus récentes. Tout au long des études, des grands panels d'isolats ont été utilisés pour représenter la diversité intraspécifique. Stimulants défavorables tels que le choc froid et la privation d'éléments nutritifs induits par l'étape d'adhésion bactérienne. L'ajout de NaCl aux cultures de croissance a stimulé la production de biofilm et, de manière surprenante, il a considérablement intensifié la maturation du biofilm de cellules privées de nutriments. Un degré élevé de variation de la productivité relative du biofilm a été observé parmi les sérotypes, les génotypes, de même que les isolats selon les conditions de culture. Cependant, un certain génotype (complexe clonal 26) a révélé de manière caractéristique une production de biofilm plus élevée à froid (10°C), suggérant une association du génotype avec le phénotype du biofilm. Pan-GWAS a identifié un certain nombre de gènes parmi lesquels ceux impliqués dans des fonctions telles que la ‘transformation/compétence’, les ‘gènes liés aux phages’ et le ‘métabolisme du phosphate’ devront faire l'objet d'études plus approfondies sur leur rôle dans la formation du biofilm. L'analyse du séquençage de l'ARN a révélé une grande hétérogénéité intraspécifique dans les profils de transcriptome basal qui mettaient en évidence le rôle du réseau de régulation, y compris certains facteurs transcriptionnels avec des rôles clés dans la virulence tels que σB, PrfA, et CodY. La plasticité transcriptomique entre les lignées I et II ainsi que les génotypes hyper et hypovirulents ont confirmé les caractéristiques évolutives et épidémiologiques de L. monocytogenes. De plus, la voie métabolique centrale a été impliquée dans l'infection dans le système modèle de Galleria mellonella. En conclusion, la thèse a exploré la diversité intraspécifique de L. monocytogenes et a donné lieu à de nombreux résultats phénotypiques, génomiques et transcriptomiques. Grâce à l'approche intégrative des omiques en listeriologie, le présent travail contribuera à dévoiler la physiologie et la pathogenèse de la bactérie
Conditions and proliferation in a wide range of environments from soil to mammalian host cells. The genetic heterogeneity in L. monocytogenes is reflected on its diversified clonal structure which correlates, to some extent, with phenotypic traits such as virulence or stress resistance. The thesis investigated two most prominent phenotypes, biofilm formation and virulence potential, from various perspectives using state-of-the art technologies. Throughout the studies, large panels of isolates were used to represent the intraspecific diversity. Unfavourable stimuli such as cold shock and nutrient deprivation induced bacterial adhesion step. Addition of NaCl to growth cultures stimulated biofilm production and, surprisingly, it significantly intensified biofilm maturation of nutrient-deprived cells. High degree of variation in relative biofilm productivity was observed among serotypes, genotypes, as well as isolates across culture conditions, however, certain genotype (clonal complex 26) revealed distinctively higher biofilm production under cold temperature (10°C) suggesting an association of genotype with biofilm phenotype. Pan-GWAS identified a number of genes among which those implicated in functions such as ‘transformation/competence’, ‘phage-related genes’, and ‘metabolism of phosphate’ will need further investigations for their roles in biofilm formation. RNA sequencing analysis revealed high intraspecific heterogeneity in basal transcriptome profiles that featured the role of regulatory network including certain transcriptional factors with key roles in virulence such as σB, PrfA, and CodY. The transcriptomic plasticity between lineage I and II as well as hyper- and hypovirulent genotypes supported the evolutionary and epidemiological characteristics of L. monocytogenes. Moreover, the central metabolic pathway was implicated in the infection in Galleria mellonella model system. Conclusively, the thesis explored intraspecific diversity in L. monocytogenes and resulted in ample phenotypic, genomic, and transcriptomic findings. With the integrative omics approach in listeriology, the present work will contribute to unveiling the physiology and pathogenesis of the bacterium

APA, Harvard, Vancouver, ISO, and other styles

35

Siqueira, Franciele Maboni. "Análise genômica e transcricional comparativa de Mycoplasma hyopneumoniae, Mycoplasma flocculare e Mycoplasma hyorhinis." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/143434.

Full text

Abstract:

Mycoplasma hyopneumoniae, Mycoplasma flocculare e Mycoplasma hyorhinis são capazes de aderir e colonizar o trato respiratório de suínos. Enquanto a presença de M. flocculare é considerada assintomática, M. hyopneumoniae e M. hyorhynis são relacionados ao desenvolvimento de patologias. M. hyopneumoniae é o agente etiológico da pneumonia enzoótica suína e M. hyorhynis além dos pulmões pode atingir outros sítios e hospedeiros, estando relacionado a artrites, poliserosites e desenvolvimento de vários tipos de câncer em humanos. Apesar dos avanços tecnológicos na área de genômica, raros são os dados quanto ao papel de M. flocculare no trato respiratório suíno. Além do mais, informações relativas à transcrição gênica nessas espécies são escassas, apesar da importância desses microrganismos. Neste estudo são apresentados os dados da sequência do genoma de uma linhagem de M. flocculare, bem como do genoma de um novo isolado de M. hyopneumoniae. Com estas novas sequências foram realizadas análises de genômica comparativa visando a identificação de características que pudessem explicar os diferentes comportamentos quanto à patogenicidade dessas espécies. Além disso, a análise global dos transcritomas de cada uma das espécies foi realizada e o perfil transcricional entre M. hyopneumoniae, M. flocculare e M. hyorhynis foi analisado comparativamente objetivando identificar características peculiares para cada um dos mapas transcricionais, além de compreender a coordenação do modo de transcrição gênica em Mycoplasma. De um modo geral, as três espécies de Mycoplasma que habitam o trato respiratório suíno possuem grandes semelhanças na composição gênica, assim como na abundância de transcritos. A análise do repertório transcricional, mostra que os genomas são transcritos quase que em sua totalidade, incluindo as regiões intergênicas, nas três espécies. M. hyopneumoniae e M. flocculare apresentam conteúdo gênico e perfil transcricional muito semelhantes. Uma importante diferença encontrada entre estas duas espécies refere-se à presença exclusiva de genes e transcritos de adesinas específicas. M. hyorhynis possui genes e transcritos exclusivos, os quais sabidamente estão relacionados à sua capacidade mutacional, de invasividade e infecção de diferentes sítios. Por fim, a análise comparativa dos genomas, e a obtenção dos mapas transcricionais para M. hyopneumoniae, M. flocculare e M. hyorhynis, foram abordagens que resultaram em um grande número de informações, as quais são importantes para embasamento de futuros estudos de caracterização dos mecanismos moleculares, como os eventos de regulação da transcrição gênica, no gênero Mycoplasma.
Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Mycoplasma flocculare are able to adhere and to colonize the swine respiratory tract. While M. flocculare presence is virtually assymptomatic, M. hyopneumoniae and M. hyorhynis infections may cause respiratory disease. M. hyopneumoniae is the causative agent of swine enzootic pneumonia and M. hyorhynis may affect the lungs and other sites in a diversity of hosts and has been related to arthritis, poliserosites and to the development of several types of human cancer. Despite genomics technological advances, there are very few data about the possible role of M. flocculare in the swine respiratory tract. Moreover, little information about gene transcription is available in these species, despite the importance of these microorganisms. In this work the genome sequences of M. flocculare and a new isolate of M. hyopneumoniae are presented. A comparative genomic analyzes was performed to identify possible characteristics that may help to explain the different behaviors of these species in the swine respiratory tracts. Furthermore, a transcriptome map of each species was performed and a comparative transcriptional profile analysis between M. hyopneumoniae, M. flocculare and M. hyorhynis was undertaken to identify the exclusive features for each of the transcriptional maps, in addition to understanding the coordination mode of gene transcription in Mycoplasma. In general, the three Mycoplasma species that inhabit the swine respiratory tract have a similar gene composition as well as the abundance of transcripts. The transcriptome maps showed that most of the predicted genes are transcribed from these Mycoplasma genomes, as well as some intergenic regions. M. hyopneumoniae and M. flocculare present very similar gene content and transcriptional profile. However, an important difference between these two species is related to the exclusive presence of genes and transcripts of some specific adhesins. M. hyorhynis presents exclusive genes and transcripts that have been related to its invasiveness, mutation rate and infection of different sites. Finally, the comparative analysis of the genomes and transcriptional maps between M. hyopneumoniae, M. flocculare and M. hyorhynis have resulted in a large amount of information, which are important for future studies of the molecular characterization, as transcriptional regulation in the Mycoplasma spp.

APA, Harvard, Vancouver, ISO, and other styles

36

Terhoeven, Niklas [Verfasser], Jörg [Gutachter] Schultz, Rainer [Gutachter] Hedrich, and Dirk [Gutachter] Becker. "Genomics of carnivorous Droseraceae and Transcriptomics of Tobacco pollination as case studies for neofunctionalisation of plant defence mechanisms / Niklas Terhoeven ; Gutachter: Jörg Schultz, Rainer Hedrich, Dirk Becker." Würzburg : Universität Würzburg, 2020. http://d-nb.info/1220227978/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Ullrich, Sophie. "Genomic and transcriptomic characterization of novel iron oxidizing bacteria of the genus “Ferrovum“." Doctoral thesis, Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola", 2016. http://nbn-resolving.de/urn:nbn:de:bsz:105-qucosa-205981.

Full text

Abstract:

Acidophilic iron oxidizing bacteria of the betaproteobacterial genus “Ferrovum” are ubiquitously distributed in acid mine drainage (AMD) habitats worldwide. Since their isolation and maintenance in the laboratory has proved to be extremely difficult, members of this genus are not accessible to a “classical” microbiological characterization with exception of the designated type strain “Ferrovum myxofaciens” P3G. The present study reports the characterization of “Ferrovum” strains at genome and transcriptome level. “Ferrovum” sp. JA12, “Ferrovum” sp. PN-J185 and “F. myxofaciens” Z-31 represent the iron oxidizers of the mixed cultures JA12, PN-J185 and Z-31. The mixed cultures were derived from the mine water treatment plant Tzschelln close to the lignite mining site in Nochten (Lusatia, Germany). The mixed cultures also contain a heterotrophic strain of the genus Acidiphilium. The genome analysis of Acidiphilium sp. JA12-A1, the heterotrophic contamination of the mixed culture JA12, indicates an interspecies carbon and phosphate transfer between Acidiphilium and “Ferrovum” in the mixed culture, and possibly also in their natural habitat. The comparison of the inferred metabolic potentials of four “Ferrovum” strains and the analysis of their phylogenetic relationships suggest the existence of two subgroups within the genus “Ferrovum” (i.e. the operational taxonomic units OTU-1 and OUT-2) harboring characteristic metabolic profiles. OTU-1 includes the “F. myxofaciens” strains P3G and Z-31, which are predicted to be motile and diazotrophic, and to have a higher acid tolerance than OTU-2. The latter includes two closely related proposed species represented by the strains JA12 and PN-J185, which appear to lack the abilities of motility, chemotaxis and molecular nitrogen fixation. Instead, both OTU-2 strains harbor the potential to use urea as alternative nitrogen source to ammonium, and even nitrate in case of the JA12-like species. The analysis of the genome architectures of the four “Ferrovum” strains suggests that horizontal gene transfer and loss of metabolic genes, accompanied by genome reduction, have contributed to the evolution of the OTUs. A trial transcriptome study of “Ferrovum” sp. JA12 supports the ferrous iron oxidation model inferred from its genome sequence, and reveals the potential relevance of several hypothetical proteins in ferrous iron oxidation. Although the inferred models in “Ferrovum” spp. share common features with the acidophilic iron oxidizers of the Acidithiobacillia, it appears to be more similar to the neutrophilic iron oxidizers Mariprofundus ferrooxydans (“Zetaproteobacteria”) and Sideroxydans lithotrophicus (Betaproteobacteria). These findings suggest a common origin of ferrous iron oxidation in the Beta- and “Zetaproteobacteria”, while the acidophilic lifestyle of “Ferrovum” spp. may have been acquired later, allowing them to also colonize acid mine drainage habitats.

APA, Harvard, Vancouver, ISO, and other styles

38

Camprubí, Font Carla. "Genetics and transcriptomics of adherent-invasive Escherichia coli (AIEC): new approaches to uncover molecular markers for its rapid identification." Doctoral thesis, Universitat de Girona, 2019. http://hdl.handle.net/10803/672302.

Full text

Abstract:

The adherent-invasive Escherichia coli (AIEC) pathotype could play a role in the course of Crohn’s disease. This is characterized by its capacity to adhere to and to invade intestinal epithelial cells as well as to replicate and survive within macrophages. At present, identification of the AIEC pathotype relies on time-consuming techniques based on the phenotypic screening of cultured bacteria, which are not standardized. In this thesis, we focused on the study of AIEC genetics in order to look for key characteristics that could assist the development of a molecular tool for the identification of the pathotype. To sum up, the results of this work provide meaningful information that contributes to our understanding of AIEC genomics. In this case, two putative molecular markers resulting from a combination of genetic and/or phenotypic features have been presented and these could assist in AIEC screening. Finally, gene expression results provide new insights to better describe genes putatively involved in AIEC virulence
El patotip adherent-invasiu d’Escherichia coli (AIEC) podria jugar un paper en el transcurs de la malaltia de Crohn. Aquest es caracteritza per tenir capacitat d’adhesió i invasió a cèl·lules de l’epiteli intestinal a més de replicar-se i sobreviure en macròfags. Actualment la única manera d’identificar aquests bacteris és analitzant aquestes característiques fenotípiques, un mètode poc estandarditzat i que requereix molt temps i dedicació. En la present tesi ens hem centrat en estudiar genèticament el patotip AIEC per tal de buscar característiques clau que puguin ajudar en el desenvolupament d’una eina molecular per a la seva identificació. En resum, els resultats d'aquest treball proporcionen informació significativa que contribueix a la comprensió de la genètica del patotip AIEC. En aquest cas, s'han presentat dos possibles marcadors moleculars resultants d'una combinació de característiques genètiques i/o fenotípiques que podrien ajudar en la detecció d’AIEC. Finalment, els resultats d'expressió gènica proporcionen noves idees per descriure millor els gens implicats en la virulència del patotip AIEC
Programa de Doctorat en Biologia Molecular, Biomedicina i Salut

APA, Harvard, Vancouver, ISO, and other styles

39

Ebenezer, ThankGod Echezona. "The genome of Euglena gracilis : annotation, function and expression." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/275885.

Full text

Abstract:

Euglena gracilis is a species of unicellular photosynthetic flagellate that inhibits aquatic ecosystems. E. gracilis belongs to the supergroup Excavata, and are an important component of the global biosphere, have biotechnological potential and is useful biological model due to their evolutionary history and complex biology. Whilst the evolutionary position of E. gracilis is now clear, their relationship with other protists such as Naegleria, Giardia, and Kinetoplastids, remains to be investigated in detail. Investigating and understanding the biology of this complex organism is a promising way to approach many evolutionary puzzles, including secondary endosymbiotic events and the evolution of parasitism, due to their relationship with Kinetoplastids. Here, I report a draft genome for E. gracilis, together with a high quality transcriptome and proteomic analysis. The estimated genome size is ~ 2 Gbp, with a GC content of ~ 50 % and a protein coding potential predicted at 36,526 Open Reading Frames (ORFs). Less than 25% of the genome is single copy sequence, indicating extensive repeat structure. There are evidences for large number of paralogs amongst specific gene families, indicating expansions and possible polyploidy as well as extensive sharing of genes with other non photosynthetic and photosynthetic eukaryotes: red and green algael genes, together with trypanosomes and other members of the excavates. Functional resolution into several of the biological systems indicates multiple similarities with the trypanosomatids in terms of orthology, paralogy, relatedness and complexity. Several biological systems such as nuclear architecture (e.g. chromosome segregation, nuclear pore complex, nuclear lamins), protein trafficking, translation, surface, consist of conserved and divergent components. For instance, several gene families likely associated with the cell surface and signal transduction possess very large numbers of lineage-specific paralogs, suggesting great flexibility in environmental monitoring and, together with divergent mechanisms for metabolic control, novel solutions to adaptation to extreme environments. I also demonstrate that the majority of control of protein expression levels is post-transcriptional and absence of transcriptional regulation, despite the presence of conventional introns. These data are a major advance in the understanding of the nuclear genome of Euglenids and provide a platform for investigation of the contributions of E. gracilis and relatives to the biosphere.

APA, Harvard, Vancouver, ISO, and other styles

40

Kincaid, Smith Julien. "Modification des traits d'histoire de vie au cours de l’hybridation et analyse des mécanismes moléculaires sous- jacents chez les parasites plathelminthes du genre Schistosoma." Thesis, Perpignan, 2018. http://www.theses.fr/2018PERP0028/document.

Full text

Abstract:

Les changements globaux ont en partie pour effet de modifier les aires de répartition géographique des espèces. Les interactions nouvelles entre espèces n’ayant jamais été en contact peuvent potentiellement mener à des cas atypiques de reproduction, notamment l’hybridation. Ce phénomène peut avoir des implications épidémiologiques fortes car il peut conduire à la genèse de pathogènes hybrides. La combinaison du matériel génétique d’espèces distinctes peut conférer de meilleures capacités à la progéniture (vigueur hybride ou hétérosis), pouvant à terme potentiellement mener à des changements adaptatifs et à l'émergence de pathogènes dans des zones non endémiques, ce qui en fait une menace émergente à l’échelle mondiale. Ce travail de thèse se focalise sur la schistosomiase, seconde maladie parasitaire humaine et sa récente émergence en Europe (Corse, France). Après l’identification et la caractérisation génomique d’un parasite hybride entre deux agents distincts de la maladie, S. haematobium chez l’homme et S. bovis chez les bovins, nous avons mené une approche intégrative afin de caractériser à plusieurs échelles les capacités invasives et la virulence de tels parasites. A partir de souches du terrain, nous avons mis en place un protocole d’évolution expérimentale visant à générer des hybrides de première et deuxième générations au laboratoire. Nous avons analysé les modifications de traits d’histoire de vie de ces parasites ainsi que les conséquences moléculaires (génomique et transcriptomique) de ce « clash génomique » et nous montrons que l’hybridation peut être une force évolutive majeure pour les parasites
Global changes contribute in modifying species geographical distribution. New interactions between species that have never been in contact before can potentially lead to atypical cases of reproduction, including hybridization. This phenomenon can have strong epidemiological consequences as it can potentially lead to the genesis of hybrid pathogens. The combination of genetic material of distinct species can confer increased capacities to the offspring (hybrid vigor or heterosis), eventually leading to adaptive changes and the emergence of pathogens in non-endemic areas, making them an emerging global threat. This thesis work focuses on schistosomiasis, the second human parasitic disease after malaria and its recent emergence in Europe (Corsica, France). After the identification and genomic characterization of a hybrid parasite between two distinct agents of the disease, S. haematobium in humans and S. bovis in cattle, we conducted an integrative approach to characterize at several scales the invasive capacities and virulence of such parasites. Starting from the field, we set up an experimental evolution protocol aimed at generating first- and second-generation hybrids in the laboratory. We analysed life history trait modifications of these parasites as well as the molecular consequences (genomics and transcriptomics) of this "genomic clash" and we show that hybridization can be a major evolutionary force for parasites

APA, Harvard, Vancouver, ISO, and other styles

41

Nikolayeva, Iryna. "Network and machine learning approaches to dengue omics data." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB032/document.

Full text

Abstract:

Les 20 dernières années ont vu l'émergence de technologies de mesure puissantes, permettant l'analyse omique de diverses maladies. Ils fournissent souvent des moyens non invasifs pour étudier l'étiologie des maladies complexes nouvellement émergentes, telles que l'infection de la dengue, transmise par les moustiques. Ma thèse se concentre sur l'adaptation et l'application d'approches utilisant des réseaux d'interaction de gènes et l'apprentissage automatique pour l'analyse de données génomiques et transcriptomiques. La première partie va au-delà d'une analyse pangénomique précédemment publiée de 4 026 personnes en appliquant une analyse de réseaux d'interaction pour trouver des groupes de gènes qui interagissent dans un réseau d'interactions fonctionnelles et qui, pris ensemble, sont associés à la dengue sévère. Dans cette partie, j'ai d'abord recalculé les valeurs-p d'association des polymorphismes séquencés, puis j'ai travaillé sur le mapping des polymorphismes à des gènes fonctionnellement apparentés, et j'ai enfin exploré différentes bases de données de voies métaboliques et d'interactions génétiques pour trouver des groupes de gènes qui, pris ensemble, sont associés à la dengue sévère. La deuxième partie de ma thèse dévoile une approche théorique pour étudier un biais dans les algorithmes de recherche de réseau actifs. Mon analyse théorique suggère que le meilleur score de sous-réseaux d'une taille donnée devrait être normalisé en fonction de la taille, selon l'hypothèse selon laquelle il s'agit d'un échantillon d'une distribution de valeur extrême, et non un échantillon de la distribution normale, comme c'est généralement le cas dans la littérature. Je propose alors une solution théorique à ce biais. La troisième partie présente un nouvel outil de recherche de sous-réseaux que j'ai co-conçu. Son modèle sous-jacent et l'algorithme évite le biais de taille trouvé dans les méthodes existantes et génère des résultats facilement compréhensibles. Je présente une application aux données transcriptomiques de la dengue. Dans la quatrième et dernière partie, je décris l'identification d'un biomarqueur qui détecte la sévérité de la dengue à l'arrivée à l'hôpital en utilisant une nouvelle approche d'apprentissage automatique. Cette approche combine la régression monotone bidimensionnelle avec la sélection des variables. Le modèle sous-jacent va au-delà des approches linéaires couramment utilisées, tout en permettant de contrôler le nombre de transcrits dans le biomarqueur. Le petit nombre de transcrits accompagné de leur représentation visuelle maximisent la compréhension et l'interprétation du biomarqueur par les professionnels de la biomédecine. Je présente un biomarqueur à 18 gènes qui permet de distinguer, à leur arrivée à l'hôpital, les patients qui vont développer des symptômes de dengue sévères de ceux qui auront une dengue non sévère. Ce biomarqueur a une performance prédictive élevée et robuste. La performance prédictive du biomarqueur a été confirmée sur deux ensembles de données qui ont tous deux utilisé différentes technologies transcriptomiques et différents sous-types de cellules sanguines
The last 20 years have seen the emergence of powerful measurement technologies, enabling omics analysis of diverse diseases. They often provide non-invasive means to study the etiology of newly emerging complex diseases, such as the mosquito-borne infectious dengue disease. My dissertation concentrates on adapting and applying network and machine learning approaches to genomic and transcriptomic data. The first part goes beyond a previously published genome-wide analysis of 4,026 individuals by applying network analysis to find groups of interacting genes in a gene functional interaction network that, taken together, are associated to severe dengue. In this part, I first recalculated association p-values of sequences polymorphisms, then worked on mapping polymorphisms to functionally related genes, and finally explored different pathway and gene interaction databases to find groups of genes together associated to severe dengue. The second part of my dissertation unveils a theoretical approach to study a size bias of active network search algorithms. My theoretical analysis suggests that the best score of subnetworks of a given size should be size-normalized, based on the hypothesis that it is a sample of an extreme value distribution, and not a sample of the normal distribution, as usually assumed in the literature. I then suggest a theoretical solution to this bias. The third part introduces a new subnetwork search tool that I co-designed. Its underlying model and the corresponding efficient algorithm avoid size bias found in existing methods, and generates easily comprehensible results. I present an application to transcriptomic dengue data. In the fourth and last part, I describe the identification of a biomarker that detects dengue severity outcome upon arrival at the hospital using a novel machine learning approach. This approach combines two-dimensional monotonic regression with feature selection. The underlying model goes beyond the commonly used linear approaches, while allowing controlling the number of transcripts in the biomarker. The small number of transcripts along with its visual representation maximize the understanding and the interpretability of the biomarker by biomedical professionals. I present an 18-gene biomarker that allows distinguishing severe dengue patients from non-severe ones upon arrival at the hospital with a unique biomarker of high and robust predictive performance. The predictive performance of the biomarker has been confirmed on two datasets that both used different transcriptomic technologies and different blood cell subtypes

APA, Harvard, Vancouver, ISO, and other styles

42

Arista, Gautier. "Génomique comparative et fonctionnelle de familles de gènes liés au métabolisme secondaire de la vigne (Vitis vinifera) et de ses proches parents." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ010/document.

Full text

Abstract:

La vigne (Vitis vinifera) possède un métabolisme secondaire particulièrement riche donnant naissance à une large palette de molécules dont certaines sont impliquées dans les défenses contre les pathogènes et d'autres dans la grande diversité d’arômes qui fait la renommée des vins. L’analyse de la séquence de référence du génome de la vigne a permis de mettre en évidence une remarquable expansion de certaines familles de gènes liés au métabolisme secondaire par rapport aux autres plantes. Dans ce travail, j'ai étudié les familles gènes codant pour les cytochromes P450, dont certains sont impliqués dans la production d’arômes, les gènes codant pour les stilbènes synthases (STS), les endo-β-1,3-glucanases et les gènes de résistance de type NBS impliqués dans les défenses de la vigne. Ma thèse vise à proposer des hypothèses expliquant l’organisation structurale de ces familles de gènes et ainsi à mieux comprendre pourquoi certaines familles présentent une amplification dans le génome de la vigne. Des approches bioinformatiques ont été utilisées afin d’étudier ces différentes familles de gènes. Les gènes cytochromes P450 et gènes R de type NBS ont tout d'abord été annotés de manière manuelle dans le génome de référence de la vigne. L’expression des gènes endo-β-1,3- glucanases, STS et cytochromes P450 a été analysée en utilisant une approche transcriptomique à grande échelle. Pour ce faire, un outil a été développé durant cette thèse pour estimer le niveau d’expression des gènes à partir de données RNA-Seq disponibles dans les banques de données publiques. Parallèlement, des données de reséquençage d’ADN de 56 cépages et espèces de vigne ont été analysées, afin de déterminer les variations structurales de type CNV au sein des familles de gènes à domaine NBS et de gènes STS. Ces différents travaux ont permis de montrer que l’amplification des familles de gènes étudiées n’est pas spécifique du génome de référence mais est retrouvée dans l'ensemble du genre Vitis, mais également de mettre en évidence des variations structurales au sein des différents génomes étudiés. L'analyse de la famille STS a montré que ces gènes sont organisés en blocs de duplication, et que les gènes plus conservés sont aussi les plus exprimés. Nous avons également montré que les gènes à domaine NBS sont organisés en cluster, dont certains sont particulièrement soumis à variation. Ces travaux contribuent à une meilleure connaissance de facteurs de défense efficaces et durables ainsi que des gènes impliqués dans la synthèse d’arômes dans la vigne. Ces connaissances pourront bénéficier aux programmes de création variétale mis en œuvre à l’INRA de Colmar
Grapevine (Vitis vinifera) has a particularly rich secondary metabolism, giving rise to a wide range of molecules, some of which are involved in defences against pathogens and others in the great diversity of aromas that make wines famous. Analysis of grapevine reference genome has shown a remarkable expansion of certain families of genes linked to secondary metabolism in comparison with the other plants. In this work, I have analysed gene families coding for cytochromes P450, some of them being involved in the production of aromas, genes coding for stilbene synthases (STS), endo-β-1,3-glucanases and NBS type resistance genes involved in grapevine defences. My thesis intends to propose hypothesis to explain the structural organisation of these families and therefore better understand why some of these families are amplified in the grapevine genome. Bioinformatic approaches have been used to study these different genes families. The cytochromes P450 and R genes of NBS type were manually annotated to improve the knowledge of these families of genes. The expression of endo-β-1,3-glucanases, STS and cytochromes P450 genes has been quantified using a large-scale transcriptomic approach. To this purpose, a tool has been developed during this thesis to estimate the level of genes expression from RNA- Seq data available in public databases. In the meantime, DNA resequencing data from 56 cultivars and grapevine species have been analysed to identify structural variations of CNV types within the genes with a NBS domain and the STS genes. These works showed that the amplification of the gene families of interest was not specific to the reference genome but occurred at the scale of the Vitis genus, but also to highlighted structural variations in different genomes. Regarding the STS genes, blocks of duplication and more conserved and expressed genes were identified. For the genes with NBS domain, a clustered organisation has been highlighted with some clusters varying more than others in the studied genotypes. These works contribute to a better knowledge of gene families for efficient and durable defence against pathogens and optimal aromas synthesis in grapevine. This knowledge will benefit to breeding programs currently in progress at INRA Colmar

APA, Harvard, Vancouver, ISO, and other styles

43

Mittal, Vinay K. "Detection and characterization of gene-fusions in breast and ovarian cancer using high-throughput sequencing." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/54014.

Full text

Abstract:

Gene-fusions are a prevalent class of genetic variants that are often employed as cancer biomarkers and therapeutic targets. In recent years, high-throughput sequencing of the cellular genome and transcriptome have emerged as a promising approach for the investigation of gene-fusions at the DNA and RNA level. Although, large volumes of sequencing data and complexity of gene-fusion structures presents unique computational challenges. This dissertation describes research that first addresses the bioinformatics challenges associated with the analysis of the massive volumes of sequencing data by developing bioinformatics pipeline and more applied integrated computational workflows. Application of high-throughput sequencing and the proposed bioinformatics approaches for the breast and ovarian cancer study reveals unexpected complex structures of gene-fusions and their functional significance in the onset and progression of cancer. Integrative analysis of gene-fusions at DNA and RNA level shows the key importance of the regulation of gene-fusion at the transcription level in cancer.

APA, Harvard, Vancouver, ISO, and other styles

44

Suarez, Ulloa Maria Victoria. "Transcriptomic and Epigenetic Responses to Environmental Stress in Marine Bivalves with a Focus on Harmful Algal Blooms." FIU Digital Commons, 2017. http://digitalcommons.fiu.edu/etd/3461.

Full text

Abstract:

Global change poses new threats for life in the oceans forcing marine organisms to respond through molecular acclimatory and adaptive strategies. Although bivalve molluscs are particularly tolerant and resilient to environmental stress, they must now face the challenge of more frequent and severe Harmful Algal Blooms (HABs) episodes. These massive outbreaks of microalgae produce toxins that accumulate in the tissues of these filter-feeder organisms, causing changes in their gene expression profiles, which in turn modify their phenotype in order to maintain homeostasis. Such modifications in gene expression are modulated by epigenetic mechanisms elicited by specific environmental stimuli, laying the foundations for long-term adaptations. The present work aims to examine the links between environmental stress in bivalve molluscs (with especial emphasis on Harmful Algal Blooms) and specific epigenetic marks triggering responses through modifications in gene expression patterns. Overall, a better understanding of the molecular strategies underlying the conspicuous stress tolerance observed in bivalve molluscs will provide a framework for developing a new generation of biomonitoring strategies. In addition, this strategy will represent a valuable contribution to our knowledge in acclimatization, adaptation and survival. With that goal in mind, the present work has generated transcriptomic data using RNA-Seq and microarray technologies, facilitating the characterization and investigation of the epigenetic mechanisms used by the Mediterranean mussel Mytilus galloprovincialis during responses to HAB exposure. That information was made publicly available through a specialized online resource (the Chromevaloa Database, chromevaloa.com) assessing the response of chromatin-associated transcripts to Okadaic Acid. Specific epigenetic marks have been assessed under lab-controlled exposure experiments simulating the natural development of the HAB Florida Red Tide (FRT). Results demonstrate a role for the phosphorylation of histone H2A.X and DNA methylation in the response to FRT in the Eastern oyster Crassostrea virginica. Lastly, the study of co-expression networks based on RNA-Seq data series from the Pacific oyster Crassostrea gigas reveals dynamic transcriptomic patterns that vary with time, stressor and tissue. However, consistent functional profiles support the existence of a core response to general conditions of environmental stress. Such response involves metabolic and transport processes, response to oxidative stress and protein repair or disposal, as well as the activation of immune mechanisms supporting a tightly intertwined neuroendocrine-immune regulatory system in bivalves.

APA, Harvard, Vancouver, ISO, and other styles

45

Rahi, Md Lifat. "Understanding the molecular basis of adaptation to freshwater environments by prawns in the genus Macrobrachium." Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/118051/1/8741018_md_lifat_rahi_thesis.pdf.

Full text

Abstract:

Understanding the processes that drive adaptive change in response to environmental variation and their consequences for speciation have long been key questions in evolutionary biology. Following origins in seawater, a number of animal groups invaded and colonized freshwater successfully over various evolutionary timeframes. Crustaceans represent a group of relatively recent colonizers of freshwater that now show extensive diversity with representative taxa found in virtually all aquatic environments. Macrobrachium (Family: Palaemonidae) are one of the most speciose and diversified of all crustacean lineages. Taxa in the genus Macrobrachium occupy a wide range of aquatic habitats, possess relatively large body size, and many are highly abundant. Macrobrachium species, as relatively recent freshwater colonizers, therefore provide excellent models for deciphering mechanisms that have facilitated freshwater adaptation. Modern genomic technologies now allow identification of genomic regions influencing adaptation and adaptive diversification (or speciation) at a finer scale. The current study employed a comparative genomics approach to investigate the molecular basis of freshwater adaptation in this decapod crustacean group. In the first study, a transcriptomic scan was performed to identify potential candidate genes involved in freshwater adaptation using an obligate freshwater species, M. koombooloomba as a model. M. koombooloomba was used essentially as the „control‟ because this species completes its entire life in freshwater; thus, all of the important genes affecting freshwater adaptation should be highly expressed in this species. We identified 43 candidate genes (based on BLAST matching with other species) that are likely to be important genes for adapting to a freshwater lifestyle in this species. Identified genes fell under seven broad biological categories including: osmoregulation, cell volume regulation, hemolymph regulation, water channel regulation, osmotic stress response, egg size control and control of larval developmental stage number. We used this gene list as the foundation for future studies. In the second study, we performed a comparative transcriptomics analysis of three Macrobrachium species (M. australiense, M. novaehollandiae and M. tolmerum) representing a range of salinity tolerances at various stages of the life cycle. The three species were maintained under two experimental salinity levels (0‰ and 15‰) over a period of six weeks. The study identified 59 candidate genes (all 43 identified in study 1) including 16 novel „lineage specific orphan transcripts/genes‟. A number of candidate genes (associated with osmoregulation, osmotic stress response, cell volume regulation, water channel and hemolymph regulation) showed different expression patterns between experimental salinities, while expression of others (associated with egg size control and larval development number) remained stable between salinities. Novel genes/transcripts also showed salinity induced differential gene expression patterns. Neutrality tests on all 59 genes revealed that differentially expressed genes showed signatures of purifying selection, but other genes (those that were not differentially expressed) showed patterns consistent with strong positive selection. A few genes (osmotic stress response, cell volume and hemolymph regulatory) showed both differential expression patterns and signatures of positive selection, depending on whether the comparison was between species with similar or dissimilar life history traits. Sequences were highly conserved across species for genes that were differentially expressed between salinities. Results suggest that both plasticity of gene expression and sequence divergence in coding regions (functional mutations), act in a co-ordinated way to promote adaptation. We argue that changes to gene expression pattern play a vital role in the initial adaptive response, while efficient adaptation via mutation/s act over prolonged evolutionary time. In the third study, we conducted a physiological genomic study of the same three species used in the previous study to investigate how regulation of gene expression and body fluid (hemolymph) change with salinity level over time. Individuals from each of the three species were maintained at three experimental salinity levels (0‰, 6‰ and 12‰) for 28 days after an initial acclimation phase to a common condition (6‰) for 14 days. In total, 12 genes were investigated in this study that are involved with different biological functions (based on study 2). For the majority of genes studied (10 out of 12), expression patterns were found to be significantly different among salinity treatments. Differentially expressed genes followed a common pattern; an initial rise in expression level up to 48 hours, followed by a fall in expression up to 96 hours after which expression levels stabilized until the end of the experimental period. Changes to hemolymph osmolality showed a similar pattern to gene expression, with significant differences in hemolymph osmolality evident among salinity treatments. Results demonstrate that salinity level has a strong influence on both hemolymph osmolality and gene expression pattern in the target Macrobrachium species. We conclude that rapid changes to physiological and genomic responses likely shape initial adaptive response to variable environmental salinities. In the final experiment, we employed a comparative genomics analysis using genotyping-by-sequencing (GBS) that screened sequences in 34 Macrobrachium species representing all life history character types from different continents (i.e., replicates of independent freshwater invasions). The study identified 5,018 single nucleotide polymorphisms (SNPs) from ≈310,000 aligned nucleotides in each species. Blasting of genotypes against both the Daphnia genome and Macrobrachium transcriptomes (sourced from studies 1 and 2) showed 65% sequence matching. Blast results revealed that the matched SNPs were located in 176 discrete genes. These genes are involved in an array of diversified functional roles including osmoregulation, hemolymph regulation, cell volume regulation, water channel regulation, egg size control, larval development pattern, energy budget, metabolism, and immune response. This suggests that many interacting genes and/or genomic regions are involved with adaptation to different environmental conditions. SNPs and aligned sequences were used to construct a maximum likelihood phylogenetic tree in addition to a „neutral‟ tree for the same 34 species using the mitochondrial (mtDNA) 16S gene. Topologies of the two trees were substantially different only at the within major clade level (distinct clade for each continent) and support an earlier hypothesis of multiple independent invasions in freshwater environments by ancestral Macrobrachium species. In the GBS tree, all continental freshwater species formed monophyletic groups indicating independent invasions of freshwater, following which Macrobrachium taxa underwent adaptive genomic divergence with respect to the environments they colonized. The GBS tree strongly supported the hypothesis that freshwater adaptation across the Macrobrachium genus likely involved convergent evolution of the same set of traits; so that all global freshwater Macrobrachium species evolved similar suites of phenotypic traits due to common selection pressures associated with a freshwater lifestyle. Overall, this study provides a comprehensive data set for resolving the genomic basis of freshwater adaptation by Palaemonid prawns in the genus Macrobrachium. We infer that response from the genome (rearrangement of the whole genome) is required for successful adaptation to a novel environment with major changes in phenotypic traits (morphology, physiology and overall organismal biology.

APA, Harvard, Vancouver, ISO, and other styles

46

Hulur, Imge, Eric R. Gamazon, Andrew D. Skol, Rosa M. Xicola, Xavier Llor, Kenan Onel, Nathan A. Ellis, and Sonia S. Kupfer. "Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci." BioMed Central Ltd, 2015. http://hdl.handle.net/10150/610285.

Full text

Abstract:

BACKGROUND: Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the functional role of many of these SNPs is largely unknown and tissue-specific resources are lacking. Expression quantitative trait loci (eQTL) mapping identifies target genes of disease-associated SNPs. This study provides a comprehensive eQTL map of distal colonic samples obtained from 40 healthy African Americans and demonstrates their relevance for GWAS of colonic diseases. RESULTS: 8.4 million imputed SNPs were tested for their associations with 16,252 expression probes representing 12,363 unique genes. 1,941 significant cis-eQTL, corresponding to 122 independent signals, were identified at a false discovery rate (FDR) of 0.01. Overall, among colon cis-eQTL, there was significant enrichment for GWAS variants for IBD (Crohn's disease [CD] and ulcerative colitis [UC]) and CRC as well as type 2 diabetes and body mass index. ERAP2, ADCY3, INPP5E, UBA7, SFMBT1, NXPE1 and REXO2 were identified as target genes for IBD-associated variants. The CRC-associated eQTL rs3802842 was associated with the expression of C11orf93 (COLCA2). Enrichment of colon eQTL near transcription start sites and for active histone marks was demonstrated, and eQTL with high population differentiation were identified. CONCLUSIONS: Through the comprehensive study of eQTL in the human colon, this study identified novel target genes for IBD- and CRC-associated genetic variants. Moreover, bioinformatic characterization of colon eQTL provides a tissue-specific tool to improve understanding of biological differences in diseases between different ethnic groups.

APA, Harvard, Vancouver, ISO, and other styles

47

Martínez, Enguita David. "Identification of personalized multi-omic disease modules in asthma." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-15987.

Full text

Abstract:

Asthma is a respiratory syndrome associated with airflow limitation, bronchial hyperresponsiveness and inflammation of the airways in the lungs. Despite the ongoing research efforts, the outstanding heterogeneity displayed by the multiple forms in which this condition presents often hampers the attempts to determine and classify the phenotypic and endotypic biological structures at play, even when considering a limited assembly of asthmatic subjects. To increase our understanding of the molecular mechanisms and functional pathways that govern asthma from a systems medicine perspective, a computational workflow focused on the identification of personalized transcriptomic modules from the U-BIOPRED study cohorts, by the use of the novel MODifieR integrated R package, was designed and applied. A feature selection of candidate asthma biomarkers was implemented, accompanied by the detection of differentially expressed genes across sample categories, the production of patient-specific gene modules and the subsequent construction of a set of core disease modules of asthma, which were validated with genomic data and analyzed for pathway and disease enrichment. The results indicate that the approach utilized is able to reveal the presence of components and signaling routes known to be crucially involved in asthma pathogenesis, while simultaneously uncovering candidate genes closely linked to the latter. The present project establishes a valuable pipeline for the module-driven study of asthma and other related conditions, which can provide new potential targets for therapeutic intervention and contribute to the development of individualized treatment strategies.

APA, Harvard, Vancouver, ISO, and other styles

48

Stranneheim, Henrik. "Enabling massive genomic and transcriptomic analysis." Doctoral thesis, KTH, Genteknologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-45957.

Full text

Abstract:

In recent years there have been tremendous advances in our ability to rapidly and cost-effectively sequence DNA. This has revolutionized the fields of genetics and biology, leading to a deeper understanding of the molecular events in life processes. The rapid advances have enormously expanded sequencing opportunities and applications, but also imposed heavy strains on steps prior to sequencing, as well as the subsequent handling and analysis of the massive amounts of sequence data that are generated, in order to exploit the full capacity of these novel platforms. The work presented in this thesis (based on six appended papers) has contributed to balancing the sequencing process by developing techniques to accelerate the rate-limiting steps prior to sequencing, facilitating sequence data analysis and applying the novel techniques to address biological questions. Papers I and II describe techniques to eliminate expensive and time-consuming preparatory steps through automating library preparation procedures prior to sequencing. The automated procedures were benchmarked against standard manual procedures and were found to substantially increase throughput while maintaining high reproducibility. In Paper III, a novel algorithm for fast classification of sequences in complex datasets is described. The algorithm was first optimized and validated using a synthetic metagenome dataset and then shown to enable faster analysis of an experimental metagenome dataset than conventional long-read aligners, with similar accuracy. Paper IV, presents an investigation of the molecular effects on the p53 gene of exposing human skin to sunlight during the course of a summer holiday. There was evidence of previously accumulated persistent p53 mutations in 14% of all epidermal cells. Most of these mutations are likely to be passenger events, as the affected cell compartments showed no apparent growth advantage. An annual rate of 35,000 novel sun-induced persistent p53 mutations was estimated to occur in sun-exposed skin of a human individual. Paper V, assesses the effect of using RNA obtained from whole cell extracts (total RNA) or cytoplasmic RNA on quantifying transcripts detected in subsequent analysis. Overall, more differentially detected genes were identified when using the cytoplasmic RNA. The major reason for this is related to the reduced complexity of cytoplasmic RNA, but also apparently due (at least partly) to the nuclear retention of transcripts with long, structured 5’- and 3’-untranslated regions or long protein coding sequences. The last paper, VI, describes whole-genome sequencing of a large, consanguineous family with a history of Leber hereditary optic neuropathy (LHON) on the maternal side. The analysis identified new candidate genes, which could be important in the aetiology of LHON. However, these candidates require further validation before any firm conclusions can be drawn regarding their contribution to the manifestation of LHON.
QC 20111115

APA, Harvard, Vancouver, ISO, and other styles

49

Lemée, Jean-Michel. "Au delà des frontières du glioblastome : caractérisation de la zone péritumorale des glioblastomes." Thesis, Angers, 2015. http://www.theses.fr/2015ANGE0001/document.

Full text

Abstract:

Le glioblastome (GB) est une tumeur hétérogène, agressive devant laquelle les possibilités thérapeutiques disponibles restent limitées. L’étude de la zone péritumorale macroscopiquement normale (ZMN) des GB est essentielle à la compréhension de ses mécanismes de progression et de récidive. Le premier objectif de ce travail de Thèse a été de comparer les données de transcriptomique et de protéomique issues de l’analyse de la zone tumorale des GB dans le cadre du Projet Gliome Grand Ouest. Le taux de concordance entre les 2 modalités est faible, retrouvant toutefois comme point commun une dysrégulation de la protéine légère des neurofilaments qui pourrait servir de biomarqueur potentiel des GB. Le deuxième objectif de ce travail de Thèse a été la caractérisation de la ZMN des GB. Nous avons mis en évidence que cette zone, dont l’aspect est similaire à première vue à celui du tissu cérébral sain, n’est pas une simple zone de transition entre le GB et le tissu cérébral sain. En effet, la ZMN est une entité spécifique possédant des caractéristiques qui lui sont propres, comme la présence d’un phénotype particulier de cellules tumorales infiltrantes et de cellules stromales et une sur’expression des protéines CRYAB et H3F3A. Ce travail de Thèse a aussi été l’occasion de développer de nouvelles techniques d’imagerie per-opératoire de la ZMN, afin d’évaluer la présence d’un contingent tumoral et ainsi optimiser la qualité de la résection chirurgicale. La caractérisation de cette ZMN nous permet de mieux appréhender son implication dans la tumorogenèse et la présence de caractéristiques spécifiques de cette zone ouvre la porte à la détection de biomarqueurs spécifiques, ainsi qu’au développement de thérapies ciblées. Ce travail de Thèse a été valorisé par 2 publications, 2 articles soumis et un brevet est en cours de dépôt et d’évaluation par un cabinet de brevet
Glioblastoma (GB) is a heterogeneous andaggressive tumor, before which therapeutic options arelimited. The study of the macroscopically normalperitumoral brain zone (PBZ) of GB is essential tounderstand its mechanisms of progression andrecurrence.The first objective of this thesis work was tocompare the transcriptomic and proteomic data from theGB tumor area obtained through the “Grand Ouest”glioma Project. The concordance rate between the 2modalities is low. However, one of the common featureis the dysregulation of neurofilament light polypeptide,which could serve as a biomarker potential of GB.The second objective of this thesis was thecharacterization of the PBZ. We have shown that thisarea, similar at first glance to that of healthy braintissue, is not a simple transition area between the GBand healthy brain tissue but a specific entity withcharacteristics of its own. For example, the ZMNpresents a particular phenotype of infiltrating GB cellsand stromal cells and a surexpression of CRYAB andH3F3A proteins.This thesis work was also an opportunity todevelop new intraoperative imaging techniques of thePBZ, with the aim to assess the presence of a tumoralinfiltration and optimize the quality of the surgicalresection.The characterization of this PBZ allows us tobetter understand its involvement in tumorigenesis andthe presence of specific characteristics of this areaopens the door for the detection of specific biomarkersand the development of targeted therapies.This thesis work was led to 2 publications, 2articles submitted and a patent being evaluated andredacted by a patent office

APA, Harvard, Vancouver, ISO, and other styles

50

Pratte, Zoe A. "Investigating the Driving Mechanisms Behind Differences in Bleaching and Disease Susceptibility Between Two Scleractinian Corals, Pseudodiploria Strigosa and Diploria Labyrinthiformis." FIU Digital Commons, 2015. http://digitalcommons.fiu.edu/etd/2217.

Full text

Abstract:

Disease and bleaching are two conditions which commonly lead to coral death. Among coral species, susceptibility to disease and bleaching is variable, and Pseudodiploria strigosa tends to be diseased more than Diploria labyrinthiformis, while D. labyrinthiformis bleaches more readily. The focus of this dissertation was to investigate and compare multiple components of these two coral species, and identify how they may relate to disease and bleaching resistance. Compenetnts examined included the surface mucopolysacharide layer (SML) thickness, gene expression, microbial associates, and a white plague aquarium study. The SML thickness decresased with increasing temperature regardless of coral species, indicating that SML thickness does not likely play a role in differences between susceptablities of these two coral species. However, Diploria labyrinthiformis had a lower mortality rate at 31°C, had fewer differentially expressed genes assossiated with stress, and upregulated genes associated with innate immunity in the summer, all of which may contribute to its relative disease resistance. The bacterial associates of each coral species were also monitored. Differences between the two coral species were primarily caused by Clostridia, Gammaproteobacteria, and rare species which may contribute to the relatively higher disease susceptibility of P. strigosa. Lastly, an aquarium study suggested that a potential pathogen of the Roseobacter clade infects both D. labyrinthiformis and P. strigosa, and might be transmitted by the Cryptochiridae gall crab, indicating that potential disease vectors associated with these two coral species may also play a role in disease resistance and resilience.

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Genomics and transcriptomics'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles