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The mapping task and its various applications in next-generation sequencingOtto, Christian 27 February 2015 (has links)
The aim of this thesis is the development and benchmarking of
computational methods for the analysis of high-throughput data from
tiling arrays and next-generation sequencing. Tiling arrays have been
a mainstay of genome-wide transcriptomics, e.g., in the identification
of functional elements in the human genome. Due to limitations of
existing methods for the data analysis of this data, a novel
statistical approach is presented that identifies expressed segments
as significant differences from the background distribution and thus
avoids dataset-specific parameters. This method detects differentially
expressed segments in biological data with significantly lower false
discovery rates and equivalent sensitivities compared to commonly used
methods. In addition, it is also clearly superior in the recovery of
exon-intron structures. Moreover, the search for local accumulations
of expressed segments in tiling array data has led to the
identification of very large expressed regions that may constitute a
new class of macroRNAs.
This thesis proceeds with next-generation sequencing for which various
protocols have been devised to study genomic, transcriptomic, and
epigenomic features. One of the first crucial steps in most NGS data
analyses is the mapping of sequencing reads to a reference
genome. This work introduces algorithmic methods to solve the mapping
tasks for three major NGS protocols: DNA-seq, RNA-seq, and
MethylC-seq. All methods have been thoroughly benchmarked and
integrated into the segemehl mapping suite.
First, mapping of DNA-seq data is facilitated by the core mapping
algorithm of segemehl. Since the initial publication, it has been
continuously updated and expanded. Here, extensive and reproducible
benchmarks are presented that compare segemehl to state-of-the-art
read aligners on various data sets. The results indicate that it is
not only more sensitive in finding the optimal alignment with respect
to the unit edit distance but also very specific compared to most
commonly used alternative read mappers. These advantages are
observable for both real and simulated reads, are largely independent
of the read length and sequencing technology, but come at the cost of
higher running time and memory consumption.
Second, the split-read extension of segemehl, presented by Hoffmann,
enables the mapping of RNA-seq data, a computationally more difficult
form of the mapping task due to the occurrence of splicing. Here, the
novel tool lack is presented, which aims to recover missed RNA-seq
read alignments using de novo splice junction information. It
performs very well in benchmarks and may thus be a beneficial
extension to RNA-seq analysis pipelines.
Third, a novel method is introduced that facilitates the mapping of
bisulfite-treated sequencing data. This protocol is considered the
gold standard in genome-wide studies of DNA methylation, one of the
major epigenetic modifications in animals and plants. The treatment of
DNA with sodium bisulfite selectively converts unmethylated cytosines
to uracils, while methylated ones remain unchanged. The bisulfite
extension developed here performs seed searches on a collapsed
alphabet followed by bisulfite-sensitive dynamic programming
alignments. Thus, it is insensitive to bisulfite-related mismatches
and does not rely on post-processing, in contrast to other methods. In
comparison to state-of-the-art tools, this method achieves
significantly higher sensitivities and performs time-competitive in
mapping millions of sequencing reads to vertebrate
genomes. Remarkably, the increase in sensitivity does not come at the
cost of decreased specificity and thus may finally result in a better
performance in calling the methylation rate.
Lastly, the potential of mapping strategies for de novo genome
assemblies is demonstrated with the introduction of a new guided
assembly procedure. It incorporates mapping as major component and
uses the additional information (e.g., annotation) as guide. With this
method, the complete mitochondrial genome of Eulimnogammarus verrucosus has been
successfully assembled even though the sequencing library has been
heavily dominated by nuclear DNA.
In summary, this thesis introduces algorithmic methods that
significantly improve the analysis of tiling array, DNA-seq, RNA-seq,
and MethylC-seq data, and proposes standards for benchmarking NGS read
aligners. Moreover, it presents a new guided assembly procedure that
has been successfully applied in the de novo assembly of a
crustacean mitogenome. / Diese Arbeit befasst sich mit der Entwicklung und dem Benchmarken von
Verfahren zur Analyse von Daten aus Hochdurchsatz-Technologien, wie
Tiling Arrays oder Hochdurchsatz-Sequenzierung. Tiling Arrays bildeten
lange Zeit die Grundlage für die genomweite Untersuchung des
Transkriptoms und kamen beispielsweise bei der Identifizierung
funktioneller Elemente im menschlichen Genom zum Einsatz. In dieser
Arbeit wird ein neues statistisches Verfahren zur Auswertung von
Tiling Array-Daten vorgestellt. Darin werden Segmente als exprimiert
klassifiziert, wenn sich deren Signale signifikant von der
Hintergrundverteilung unterscheiden. Dadurch werden keine auf den
Datensatz abgestimmten Parameterwerte benötigt. Die hier
vorgestellte Methode erkennt differentiell exprimierte Segmente in
biologischen Daten bei gleicher Sensitivität mit geringerer
Falsch-Positiv-Rate im Vergleich zu den derzeit hauptsächlich
eingesetzten Verfahren. Zudem ist die Methode bei der Erkennung von
Exon-Intron Grenzen präziser. Die Suche nach Anhäufungen
exprimierter Segmente hat darüber hinaus zur Entdeckung von sehr
langen Regionen geführt, welche möglicherweise eine neue
Klasse von macroRNAs darstellen.
Nach dem Exkurs zu Tiling Arrays konzentriert sich diese Arbeit nun
auf die Hochdurchsatz-Sequenzierung, für die bereits verschiedene
Sequenzierungsprotokolle zur Untersuchungen des Genoms, Transkriptoms
und Epigenoms etabliert sind. Einer der ersten und entscheidenden
Schritte in der Analyse von Sequenzierungsdaten stellt in den meisten
Fällen das Mappen dar, bei dem kurze Sequenzen (Reads) auf ein
großes Referenzgenom aligniert werden. Die vorliegende Arbeit
stellt algorithmische Methoden vor, welche das Mapping-Problem für
drei wichtige Sequenzierungsprotokolle (DNA-Seq, RNA-Seq und
MethylC-Seq) lösen. Alle Methoden wurden ausführlichen
Benchmarks unterzogen und sind in der segemehl-Suite integriert.
Als Erstes wird hier der Kern-Algorithmus von segemehl vorgestellt,
welcher das Mappen von DNA-Sequenzierungsdaten ermöglicht. Seit
der ersten Veröffentlichung wurde dieser kontinuierlich optimiert
und erweitert. In dieser Arbeit werden umfangreiche und auf
Reproduzierbarkeit bedachte Benchmarks präsentiert, in denen
segemehl auf zahlreichen Datensätzen mit bekannten
Mapping-Programmen verglichen wird. Die Ergebnisse zeigen, dass
segemehl nicht nur sensitiver im Auffinden von optimalen Alignments
bezüglich der Editierdistanz sondern auch sehr spezifisch im
Vergleich zu anderen Methoden ist. Diese Vorteile sind in realen und
simulierten Daten unabhängig von der Sequenzierungstechnologie
oder der Länge der Reads erkennbar, gehen aber zu Lasten einer
längeren Laufzeit und eines höheren Speicherverbrauchs.
Als Zweites wird das Mappen von RNA-Sequenzierungsdaten untersucht,
welches bereits von der Split-Read-Erweiterung von segemehl
unterstützt wird. Aufgrund von Spleißen ist diese Form des
Mapping-Problems rechnerisch aufwendiger. In dieser Arbeit wird das
neue Programm lack vorgestellt, welches darauf abzielt, fehlende
Read-Alignments mit Hilfe von de novo Spleiß-Information zu
finden. Es erzielt hervorragende Ergebnisse und stellt somit eine
sinnvolle Ergänzung zu Analyse-Pipelines für
RNA-Sequenzierungsdaten dar.
Als Drittes wird eine neue Methode zum Mappen von Bisulfit-behandelte
Sequenzierungsdaten vorgestellt. Dieses Protokoll gilt als
Goldstandard in der genomweiten Untersuchung der DNA-Methylierung,
einer der wichtigsten epigenetischen Modifikationen in Tieren und
Pflanzen. Dabei wird die DNA vor der Sequenzierung mit Natriumbisulfit
behandelt, welches selektiv nicht methylierte Cytosine zu Uracilen
konvertiert, während Methylcytosine davon unberührt
bleiben. Die hier vorgestellte Bisulfit-Erweiterung führt die
Seed-Suche auf einem reduziertem Alphabet durch und verifiziert die
erhaltenen Treffer mit einem auf dynamischer Programmierung
basierenden Bisulfit-sensitiven Alignment-Algorithmus. Das verwendete
Verfahren ist somit unempfindlich gegenüber
Bisulfit-Konvertierungen und erfordert im Gegensatz zu anderen
Verfahren keine weitere Nachverarbeitung. Im Vergleich zu aktuell
eingesetzten Programmen ist die Methode sensitiver und benötigt
eine vergleichbare Laufzeit beim Mappen von Millionen von Reads auf
große Genome. Bemerkenswerterweise wird die erhöhte
Sensitivität bei gleichbleibend guter Spezifizität
erreicht. Dadurch könnte diese Methode somit auch bessere
Ergebnisse bei der präzisen Bestimmung der Methylierungsraten
erreichen.
Schließlich wird noch das Potential von Mapping-Strategien für
Assemblierungen mit der Einführung eines neuen,
Kristallisation-genanntes Verfahren zur unterstützten
Assemblierung aufgezeigt. Es enthält Mapping als Hauptbestandteil
und nutzt Zusatzinformation (z.B. Annotationen) als
Unterstützung. Dieses Verfahren ermöglichte die erfolgreiche
Assemblierung des kompletten mitochondrialen Genoms von Eulimnogammarus verrucosus trotz
einer vorwiegend aus nukleärer DNA bestehenden genomischen
Bibliothek.
Zusammenfassend stellt diese Arbeit algorithmische Methoden vor,
welche die Analysen von Tiling Array, DNA-Seq, RNA-Seq und MethylC-Seq
Daten signifikant verbessern. Es werden zudem Standards für den
Vergleich von Programmen zum Mappen von Daten der
Hochdurchsatz-Sequenzierung vorgeschlagen. Darüber hinaus wird ein
neues Verfahren zur unterstützten Genom-Assemblierung vorgestellt,
welches erfolgreich bei der de novo-Assemblierung eines
mitochondrialen Krustentier-Genoms eingesetzt wurde.
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Samma historia med olika ord : En undersökning av ett nivåanpassat läsinlärningsläromedel för årskurs 1 / The same story in different words : A study of level-based teaching materialLindström, Jennica, Olsson, Matilda January 2016 (has links)
This study examines a reader used in grade 1, Den magiska kulan, which is a part of the ABC-klubben series of teaching material. It is level-based, available in three different levels of difficulty, and one and the same class is supposed to share the same reading experience but be able to read the story at the level that each individual pupil has reached. The study analyses linguistic adaptation and elements intended to give motivation in the different books. The study shows that the simplest of the books may not help to increase the pupils’ motivation for reading but can only be regarded as training in decoding. The two more advanced books can give pupils more pleasurable reading because the language is more nuanced and expressive. The pupils thus have the chance to become absorbed in the books, with an understanding for the characters and events.
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Lactate dehydrogenase is C-terminally extended by stop codon read-through which targets this isoform into the peroxisomesGeorge, Rosemol 03 August 2016 (has links)
No description available.
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On Collective Communication and Notified Read in the Global Address Space Programming Interface (GASPI)End, Vanessa 14 December 2016 (has links)
No description available.
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A Comparison of Two Methods of Listening and Reading Training in an Eighth Grade Language Arts ProgramKraner, Robert Eugene, 1933- 08 1900 (has links)
The purpose of this study was to compare the effects of two methods of listening and reading instruction when used in the language arts programs at the eighth-grade level as related to listening, reading, study skills, and English achievement. Two groups were studied; one was an experimental group receiving programed material present by the Listen and Read Program and a control group receiving instruction through the regular classroom program.
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Prison Notes: an Introductory Study of Inmate MarginaliaHunter, Cody 12 1900 (has links)
This thesis introduces the study of inmate marginalia as a method for understanding inmates’ uses of texts in prison libraries and for understanding the motivations for these uses. Marginalia are the notes, drawings, underlining, and other markings left by readers in the texts with which they interact. I use the examples of the Talmudic projects to set a precedent for the integration of marginal discourses into the central discourse of society. Next, I discuss the arguments surrounding the use of texts in prison libraries, including an outline for an ideal study of inmate marginalia. Finally, I discuss the findings of my on-site research at four prison libraries in Washington State. After scanning evidence of marginalia from forty-eight texts, a relatively small sample, I divided the marginalia by gender of facility, genre of text, address of the marginalia, and type of marginalia and found statistically significant correlations (p < 0.05) between gender and genre, gender and address, gender and type, and genre and type. However, while these correlations are statistically weak and require further investigation, the statistically significant correlations indicate the potential for integrating inmate marginalia studies into the scholarly discussions regarding inmates’ interactions with texts in prison.
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Motivation för läsning : Hur pedagoger kan arbeta för att bygga motivation och intresse för läsundervisning / Reading motivation : How teachers can work to build motivation and interest in reading educationBergstedt, Emelie January 2019 (has links)
The purpose of this study is to survey how teachers work with reading to motivate students to raise an interest. The aim of this study is to find answers on which elements can affect students reading habits, in which ways teachers can operate to make reading education motivating and how we can operate to build an interest and a desire to read among the students. The survey has been defined to operative teachers in Karlstad kommun and students in the ages 9- 10. To implement this study both qualitative observations and qualitative interviews have occurred. Three teachers have been interviewed and their classes has been observed. The result of this study shows that, a varying education is beneficial and promotes motivation and interest amongst the students. All teachers illustrate how important reading education is and puts much effort in presenting the students a continuous instruction in reading. / Syftet med denna studie är att undersöka hur pedagoger arbetar med läsning för att motivera elever att bygga ett intresse. Studiens avsikt är att få svar på vilka faktorer som kan påverka elevernas läsning, på vilka sätt som pedagoger kan arbeta för att göra läsundervisningen motiverande samt för att bygga ett intresse och en läslust hos eleverna. Studien har centrerats till verksamma pedagoger i Karlstad kommun samt elever i åldrarna 9–10 år. För att genomföra denna studie har kvalitativa observationer samt intervjuer genomförts. Tre pedagoger har blivit intervjuade och deras klasser har observerats. Resultatet av studien visar hur varierande arbetssätt främjar motivation och intresse hos eleverna. Samtliga deltagande lärare belyser hur viktigt läsundervisning är och lägger stor vikt vid att ge eleverna en kontinuerlig undervisning kring läsning.
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Citação e alusão nas crônicas machadianas: estratégias de ler e escrever pelo avessoSantos, Erivaldo dos 27 October 2010 (has links)
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Previous issue date: 2010-10-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This dissertation deals with the quotations and allusions found in Machado s chronicles. This study focuses on the circuit of the Sermon on the Mount as a reading and writing strategy in the process of alluding and quoting; its rewriting strengths are found in inversion through irony or parody in tune with the seriocomic Lucianic lineage. Five chronicles were selected for the body of this research, namely: "Parasite II" in the "Watercolors" section of October 9th, 1859, published in The Mirror newspaper; the chronicles published in the "By chance" section of June 12nd, 1864 and 22 August 1864, in the Rio de Janeiro newspaper, and besides these, two more chronicles from September 4th , 1892 and March 25th , 1894, which were published in the " The Week" section of the Gazeta de Noticias newspaper. We raised the following question as the central issue of this study: how does Machado de Assis make use of quotations and allusions, thus emptying the canonical discourse and revealing its anti-dogmatism? We hypothesize that the use of quotations and allusions is Machdo s method of reading and writing inside out, which is based on irony and parody, so as to empty the canonical discourse of the biblical tradition, represented by the Sermon on the Mount. Our research was guided by the theoretical support on the readable and writeable text of Barthes and parody grounded in Linda Hutcheon and Bakhtin, in addition to the studies of Enylton de Sá Rego regarding the link of Machado's work with the Menippus satire genre of Lucianic lineage. After reading, analyzing and comparing the quotations and allusions of the Sermon on Mountain in selected chronicles, we believe that Machado de Assis makes uses of quotations and allusions, albeit in a lesser degree, a genre called chronicle, as the discursive strategies that aim at training the reader / Esta dissertação tem como tema a citação e a alusão na crônica machadiana. Objetiva-se estudar o circuito do Sermão da Montanha como estratégia de leitura e de escritura no processo de aludir e citar, tendo na inversão da fonte por ironia ou paródia sua força de reescritura afinada com o sério-cômico de linhagem luciânica. Cinco crônicas foram selecionadas para corpus desta pesquisa, a saber: Parasita II na seção Aquarelas de 9 de outubro 1859, publicada no periódico O Espelho; as publicadas na seção Ao acaso de 12 de junho de 1864 e de 22 de agosto de 1864, no Diário do Rio de Janeiro; além de duas outras - as de 4 de setembro de 1892 e 25 de março de 1894, publicadas na seção A Semana do periódico Gazeta de Notícias. Levantamos como problema da pesquisa a seguinte indagação: como Machado de Assis, pelo uso da citação e da alusão, esvazia o discurso canônico e revela seu antidogmatismo? Como hipótese, consideramos o uso da citação e da alusão como método machadiano de ler-escrever pelo avesso, fundado sobre a ironia e a paródia, de sorte a esvaziar o discurso canônico de tradição bíblica, representado pelo Sermão da Montanha. Norteamos a pesquisa pelo suporte teórico sobre texto legível e escriptível de Barthes e os de paródia alicerçados em Linda Hutcheon e Bakthin, além dos estudos de Enylton de Sá Rego sobre o vínculo da obra machadiana com a sátira menipeia de linhagem luciânica. Após leitura, análise e comparação entre as citações e alusões do Sermão da Montanha nas crônicas selecionadas, consideramos que Machado de Assis se utiliza de citação e alusão, ainda que num gênero considerado menor como a crônica, como estratégias discursivas que visam à formação do leitor
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Högläsning i skolan : En studie om hur tre lågstadielärare arbetar med högläsning – föreställningar och motiv / Reading aloud in school. : A study of how three teachers in the lower level of compulsory school work with reading aloud - ideas and motives.Wiezell, Linda January 2015 (has links)
The aim of the study was to investigate how teachers work with reading aloud. The aim also included examining their ideas about and motives for reading aloud. The study consisted of interviews with three teachers at the lower level of compulsory school along with observation of one of these teachers during a reading aloud session. The interviewed teachers work at three different schools in the same geographical area. The analytical tools chosen for the study were the theories of Rosenblatt. The three basic skills that Damber et al. showed children to develop through reading aloud were also used to interpret the result. The result showed that the teachers have two main purposes for the reading aloud sessions: relaxation and a structured occasion for learning. Two of the teachers use the project “A Reading Class”. The teachers say that the reading aloud creates a sense of community in the classroom when the children share the same reading experience. There are usually conversations during the sessions, but most conversations take place during the structured learning occasions. The teachers’ main motive for reading aloud is the ambition to develop an interest in books among the children, leading them into their own reading development. They want to give the children an entrance to the literary world.
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Interação coordenador pedagógico Professores: um estudo sobre leitura colaborativaPreviattelli, Wania Maria 10 March 2016 (has links)
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Previous issue date: 2016-03-10 / The present work is a research that aimed to analyze to what extent the pedagogical
coordinators, subject of training reading teaching have appropriated the principles of
collaborative/shared reading and as forwarded this discussion with teachers. The critical
incident technique were used for data collection with the pedagogical coordinators of a
Directorate of Public Education in the interior of São Paulo State. As theoretical referents
were used that deal with authors of such training as Délia Lerner, Isabel Solé, Frank Smith e
Ângela Kleiman. The analysis of the responses identified that: there are different
understandings about the purpose of the shared reading and to whom; the applicant's idea of
"help the professor" in forwards proposed by them, yet prescriptive character-based. The data
allowed the analysis of the interactions between the pedagogical coordinators with their
teachers and their consequences on pedagogical practice / O presente trabalho trata de uma pesquisa que teve como objetivo analisar em que medida os coordenadores pedagógicos, sujeitos da formação sobre didática da leitura se apropriaram dos princípios da leitura colaborativa/compartilhada e como encaminharam essa discussão junto
aos professores. Utilizou-se a técnica dos incidentes críticos para a coleta de dados junto aos
coordenadores pedagógicos de uma Diretoria de Ensino da Rede Pública Estadual do interior
de São Paulo. Como referentes teóricos foram utilizados textos de autores que tratam dessa
formação, como Délia Lerner, Isabel Solé, Frank Smith e Ângela Kleiman. A análise das
respostas permitiu identificar que: há diferentes entendimentos acerca do propósito da leitura
compartilhada e a quem se destina; a recorrente ideia de “ajuda ao professor” nos
encaminhamentos propostos por eles é ainda baseada em caráter prescritivo. Os dados
permitiram, ainda, a análise do tipo de interação entre os coordenadores pedagógicos com
seus professores e suas consequências na prática pedagógica
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