This thesis introduces three different algorithmical and statistical strategies for the analysis of high-throughput sequencing data. First, we introduce a heuristic method based on enhanced suffix arrays to map short sequences to larger reference genomes. The algorithm builds on the idea of an error-tolerant traversal of the suffix array for the reference genome in conjunction with the concept of matching statistics introduced by Chang and a bitvector based alignment algorithm proposed by Myers. The algorithm supports paired-end and mate-pair alignments and the implementation offers methods for primer detection, primer and poly-A trimming. In our own benchmarks as well as independent bench- marks this tool outcompetes other currently available tools with respect to sensitivity and specificity in simulated and real data sets for a large number of sequencing protocols. Second, we introduce a novel dynamic programming algorithm for the spliced alignment problem. The advantage of this algorithm is its capability to not only detect co-linear splice events, i.e. local splice events on the same genomic strand, but also circular and other non-collinear splice events. This succinct and simple algorithm handles all these cases at the same time with a high accuracy. While it is at par with other state- of-the-art methods for collinear splice events, it outcompetes other tools for many non-collinear splice events. The application of this method to publically available sequencing data led to the identification of a novel isoform of the tumor suppressor gene p53. Since this gene is one of the best studied genes in the human genome, this finding is quite remarkable and suggests that the application of our algorithm could help to identify a plethora of novel isoforms and genes. Third, we present a data adaptive method to call single nucleotide variations (SNVs) from aligned high-throughput sequencing reads. We demonstrate that our method based on empirical log-likelihoods automatically adjusts to the quality of a sequencing experiment and thus renders a \"decision\" on when to call an SNV. In our simulations this method is at par with current state-of-the-art tools. Finally, we present biological results that have been obtained using the special features of the presented alignment algorithm. / Diese Arbeit stellt drei verschiedene algorithmische und statistische Strategien für die Analyse von Hochdurchsatz-Sequenzierungsdaten vor. Zuerst führen wir eine auf enhanced Suffixarrays basierende heuristische Methode ein, die kurze Sequenzen mit grossen Genomen aligniert. Die Methode basiert auf der Idee einer fehlertoleranten Traversierung eines Suffixarrays für Referenzgenome in Verbindung mit dem Konzept der Matching-Statistik von Chang und einem auf Bitvektoren basierenden Alignmentalgorithmus von Myers. Die vorgestellte Methode unterstützt Paired-End und Mate-Pair Alignments, bietet Methoden zur Erkennung von Primersequenzen und zum trimmen von Poly-A-Signalen an. Auch in unabhängigen Benchmarks zeichnet sich das Verfahren durch hohe Sensitivität und Spezifität in simulierten und realen Datensätzen aus. Für eine große Anzahl von Sequenzierungsprotokollen erzielt es bessere Ergebnisse als andere bekannte Short-Read Alignmentprogramme. Zweitens stellen wir einen auf dynamischer Programmierung basierenden Algorithmus für das spliced alignment problem vor. Der Vorteil dieses Algorithmus ist seine Fähigkeit, nicht nur kollineare Spleiß- Ereignisse, d.h. Spleiß-Ereignisse auf dem gleichen genomischen Strang, sondern auch zirkuläre und andere nicht-kollineare Spleiß-Ereignisse zu identifizieren. Das Verfahren zeichnet sich durch eine hohe Genauigkeit aus: während es bei der Erkennung kollinearer Spleiß-Varianten vergleichbare Ergebnisse mit anderen Methoden erzielt, schlägt es die Wettbewerber mit Blick auf Sensitivität und Spezifität bei der Vorhersage nicht-kollinearer Spleißvarianten. Die Anwendung dieses Algorithmus führte zur Identifikation neuer Isoformen. In unserer Publikation berichten wir über eine neue Isoform des Tumorsuppressorgens p53. Da dieses Gen eines der am besten untersuchten Gene des menschlichen Genoms ist, könnte die Anwendung unseres Algorithmus helfen, eine Vielzahl weiterer Isoformen bei weniger prominenten Genen zu identifizieren. Drittens stellen wir ein datenadaptives Modell zur Identifikation von Single Nucleotide Variations (SNVs) vor. In unserer Arbeit zeigen wir, dass sich unser auf empirischen log-likelihoods basierendes Modell automatisch an die Qualität der Sequenzierungsexperimente anpasst und eine \"Entscheidung\" darüber trifft, welche potentiellen Variationen als SNVs zu klassifizieren sind. In unseren Simulationen ist diese Methode auf Augenhöhe mit aktuell eingesetzten Verfahren. Schließlich stellen wir eine Auswahl biologischer Ergebnisse vor, die mit den Besonderheiten der präsentierten Alignmentverfahren in Zusammenhang stehen.

This thesis introduces three different algorithmical and statistical strategies for the analysis of high-throughput sequencing data. First, we introduce a heuristic method based on enhanced suffix arrays to map short sequences to larger reference genomes. The algorithm builds on the idea of an error-tolerant traversal of the suffix array for the reference genome in conjunction with the concept of matching statistics introduced by Chang and a bitvector based alignment algorithm proposed by Myers. The algorithm supports paired-end and mate-pair alignments and the implementation offers methods for primer detection, primer and poly-A trimming. In our own benchmarks as well as independent bench- marks this tool outcompetes other currently available tools with respect to sensitivity and specificity in simulated and real data sets for a large number of sequencing protocols. Second, we introduce a novel dynamic programming algorithm for the spliced alignment problem. The advantage of this algorithm is its capability to not only detect co-linear splice events, i.e. local splice events on the same genomic strand, but also circular and other non-collinear splice events. This succinct and simple algorithm handles all these cases at the same time with a high accuracy. While it is at par with other state- of-the-art methods for collinear splice events, it outcompetes other tools for many non-collinear splice events. The application of this method to publically available sequencing data led to the identification of a novel isoform of the tumor suppressor gene p53. Since this gene is one of the best studied genes in the human genome, this finding is quite remarkable and suggests that the application of our algorithm could help to identify a plethora of novel isoforms and genes. Third, we present a data adaptive method to call single nucleotide variations (SNVs) from aligned high-throughput sequencing reads. We demonstrate that our method based on empirical log-likelihoods automatically adjusts to the quality of a sequencing experiment and thus renders a \"decision\" on when to call an SNV. In our simulations this method is at par with current state-of-the-art tools. Finally, we present biological results that have been obtained using the special features of the presented alignment algorithm. / Diese Arbeit stellt drei verschiedene algorithmische und statistische Strategien für die Analyse von Hochdurchsatz-Sequenzierungsdaten vor. Zuerst führen wir eine auf enhanced Suffixarrays basierende heuristische Methode ein, die kurze Sequenzen mit grossen Genomen aligniert. Die Methode basiert auf der Idee einer fehlertoleranten Traversierung eines Suffixarrays für Referenzgenome in Verbindung mit dem Konzept der Matching-Statistik von Chang und einem auf Bitvektoren basierenden Alignmentalgorithmus von Myers. Die vorgestellte Methode unterstützt Paired-End und Mate-Pair Alignments, bietet Methoden zur Erkennung von Primersequenzen und zum trimmen von Poly-A-Signalen an. Auch in unabhängigen Benchmarks zeichnet sich das Verfahren durch hohe Sensitivität und Spezifität in simulierten und realen Datensätzen aus. Für eine große Anzahl von Sequenzierungsprotokollen erzielt es bessere Ergebnisse als andere bekannte Short-Read Alignmentprogramme. Zweitens stellen wir einen auf dynamischer Programmierung basierenden Algorithmus für das spliced alignment problem vor. Der Vorteil dieses Algorithmus ist seine Fähigkeit, nicht nur kollineare Spleiß- Ereignisse, d.h. Spleiß-Ereignisse auf dem gleichen genomischen Strang, sondern auch zirkuläre und andere nicht-kollineare Spleiß-Ereignisse zu identifizieren. Das Verfahren zeichnet sich durch eine hohe Genauigkeit aus: während es bei der Erkennung kollinearer Spleiß-Varianten vergleichbare Ergebnisse mit anderen Methoden erzielt, schlägt es die Wettbewerber mit Blick auf Sensitivität und Spezifität bei der Vorhersage nicht-kollinearer Spleißvarianten. Die Anwendung dieses Algorithmus führte zur Identifikation neuer Isoformen. In unserer Publikation berichten wir über eine neue Isoform des Tumorsuppressorgens p53. Da dieses Gen eines der am besten untersuchten Gene des menschlichen Genoms ist, könnte die Anwendung unseres Algorithmus helfen, eine Vielzahl weiterer Isoformen bei weniger prominenten Genen zu identifizieren. Drittens stellen wir ein datenadaptives Modell zur Identifikation von Single Nucleotide Variations (SNVs) vor. In unserer Arbeit zeigen wir, dass sich unser auf empirischen log-likelihoods basierendes Modell automatisch an die Qualität der Sequenzierungsexperimente anpasst und eine \"Entscheidung\" darüber trifft, welche potentiellen Variationen als SNVs zu klassifizieren sind. In unseren Simulationen ist diese Methode auf Augenhöhe mit aktuell eingesetzten Verfahren. Schließlich stellen wir eine Auswahl biologischer Ergebnisse vor, die mit den Besonderheiten der präsentierten Alignmentverfahren in Zusammenhang stehen.

Massively parallel sequencing has rapidly revolutionized DNA and RNA research. Sample preparations are steadfastly advancing, sequencing costs have plummeted and throughput is ever growing. This progress has resulted in exponential growth in data generation with a corresponding demand for bioinformatic solutions. This thesis addresses methodological aspects of this sequencing revolution and applies it to selected biological topics. Papers I and II are technical in nature and concern sample preparation and data anal- ysis of RNA sequencing data. Paper I is focused on RNA degradation and paper II on generating strand specific RNA-seq libraries. Paper III and IV deal with current biological issues. In paper III, whole exomes of cancer patients undergoing chemotherapy are sequenced and their genetic variants associ- ated to their toxicity induced adverse drug reactions. In paper IV a comprehensive view of the gene expression of the endometrium is assessed from two time points of the menstrual cycle. Together these papers show relevant aspects of contemporary sequencing technologies and how it can be applied to diverse biological topics. / <p>QC 20160329</p>

Nursing as a profession presents an interesting context for studying meaning of work, as it centres on the care of patients; the motivation behind choosing such a profession. Furthermore, taking into consideration the current economic situation and the shortage of nurses in the country, it is important to investigate the kind of impact that the meaning they receive from their work may have on their commitment to the hospital and their level of engagement in their work. What nurses do and how well they do it relates directly to the quality of care the patient receives. Therefore, the objective of this study was to investigate the relationship between meaning of work, organisational commitment and work engagement among nurses of various hospitals in the Vaal Triangle. Also investigated were biographical factors such as gender, race, age, citizenship, qualification, years of service, job level and employment status. A survey design was used on a sample of nurses (N = 199) in hospitals. A biographical questionnaire, the Organisational Commitment Questionnaire, the Utrecht Work Engagement Scale and Work-Life Questionnaire were administered. The statistical analyses were carried out by means of SPSS (2009). Factor analyses were conducted to determine construct validity and Cronbach’s alphas and inter-item correlation coefficients assessed the internal consistency of the instruments. Cronbach’s alpha coefficients ranging from 0,94 to 0,62 were obtained for the above-mentioned questionnaires. Results showed that the majority of nurses viewed their work as either a job or a calling. More African nurses viewed their work as a calling than did any other race group. Younger workers, specifically those with a Grade 12 qualification, viewed their work as a career, while the more experienced nurses and those on management level viewed their work as either a career or a calling. Furthermore, nurses viewing their work as a calling are more committed to the organisation and more engaged in their work, whereas nurses viewing their work as a job are less committed and engaged. Lastly, a positive relationship exists between organisational commitment and work engagement. Therefore, the more strongly nurses view their work as a calling, the more committed they will be to the hospital and the more engaged they will be in their work. Based on the above findings, recommendations were made for the hospitals and future research. / MCom, Industrial Psychology, North-West University, Vaal Triangle Campus, 2011

Genotype microarrays assay hundreds of thousands of genetic variants on an individual's genome. The availability of this high throughput genotyping capability has transformed the field of genetics over the past decade by enabling thousands of individuals to be rapidly assayed. This has lead to the discovery of hundreds of genetic variants that are associated with disease and other phenotypes in genome wide association studies (GWAS). These data have also brought with them a number of new statistical and computational challenges. This thesis deals with two primary analysis problems involving microarray data; genotype calling and haplotype inference. Genotype calling involves converting the noisy bivariate fluorescent signals generated by microarray data into genotype values for each genetic variant and individual. Poor quality genotype calling can lead to false positives and loss of power in GWAS so this is an important task. We introduce a new genotype calling method that is highly accurate and has the novel capability of fusing microarray data with next-generation sequencing data for greater accuracy and fewer missing values. Our new method compares favourably to other available genotype calling software. Haplotype inference (or phasing) involves deconvolving these genotypes into the two inherited parental chromosomes for an individual. The development of phasing methods has been a fertile field for statistical genetics research for well over ten years. Depending on the demography of a cohort, different phasing methods may be more appropriate than others. We review the popular offerings and introduce a new approach to try and unify two distinct problems; the phasing of extended pedigrees and the phasing of unrelated individuals. We conduct an extensive comparison of phasing methods on real and simulated data. Finally we demonstrate some preliminary results on extending methodology to sample sizes in the tens of thousands.

Neste trabalho faz-se o questionamento e a caracterização do executivo, buscando inicialmente observar como seu papel pode ser compreendido de uma perspectiva sociológica, tomando a Administração de Empresas como profissão e verificando a hipótese de se enquadrar o executivo como profissional. O cargo e a função do executivo são examinados sob o ângulo da burocracia, em sentido geral e no capitalismo, e são identificadas suas competências e condutas demandadas no atual estágio de racionalização das modernas organizações, mostrando que a atuação do executivo transcende o âmbito estritamente burocrático. A vocação do executivo, dimensão \"irracional\" como no sentido de paixão, é revelada em aparente contradição com seu lado racional de planejamento ou controle do negócio e da carreira - e também disso depende sua ascensão profissional. Por fim, revela-se o executivo como portador de um capitalismo, responsável pela continuidade de um sistema de dominação racionalmente legitimado e pela reprodução e expansão do capital, para o que não raro deve promover transformações em sua própria estrutura, a organização capitalista. Nesse sentido o executivo pode nos sinalizar um novo paradigma de profissional no capitalismo moderno. / This work questions and characterizes the executive, initially trying to understand his role under a sociological perspective and Business Administration as a profession to check the hypothesis of framing executive effectively as a professional. The executive function and position are examined by the viewpoint of burocracy, both in a general sense and in special in the capitalism. His competencies and conducts required in the modern organization present stage of rationalization, to reveal that he plays a role that is beyond the mere burocratic domain. The vocation of the executive, \"non rational\" dimension as in the sense of passion, is shown in apparent contradiction to his rational business and own career control and planning - this is also decisive in his professional progress. Finally, the executive is revealed as \"carrier\" of Capitalism, responsible for the continuity de a system of authority rationally legitimated and for the reproduction and growth of capital, for which sake he must eventually promote transformations in its own structure, the capitalist organization. In so far, the executive can point out to a new professional paradigm in contemporary Capitalism.

Conversations concerning the missional posture of 1 Peter have been dictated largely by the now (in)famous debate between David Balch’s assimilationist position over and against John Elliott’s more sectarian position. More recent work has sought to bridge the gap between Balch and Elliott with a variety of more nuanced positions such as Miroslav Volf’s “Soft Difference”. Most of the discussion revolves around the practicalities of cultural engagement and what it might mean for church members to interact with the world as “Christians” in an increasingly hostile environment. The present thesis takes a step back from the coal face of missional engagement to focus on how that mission is shaped. More particularly, I am concerned with how 1 Peter utilises the language of divine calling (καλέω) that appears in five specific instances (1:13–21; 2:4–10; 2:18–25; 3:8–17; 5:6–14), alongside central events and motifs from the Old Testament, to cultivate a narrative that forges a distinct Christian identity and mission, that has its basis in Israel’s history and the life of Christ. Our concern with narrative and cultural interaction leads us to consider the relevant Petrine texts, through the dual lenses of Social Identity and Narrative Transportation theories which reveal how various groups interact, and how narratives shape actions and beliefs respectively. I argue that through the language of calling, and with the assistance of key OT motifs, 1 Peter seeks to develop a Christian identity that might be best described as “elect sojourners”; that believers are those who are elect of God and yet rejected by the world. This identity manifests itself in a life of “resident-alien-ness”—in the world, yet no longer of the world—that consequently leads to various forms of suffering. Amid such suffering, 1 Peter calls the church to a priestly ministry—representing God to the people, and the people to God—through a life geared towards blessing, even when such a life leads to suffering. This is the life to which the Anatolian believers have been called: a life of holiness as a priestly community, committed to the gracious endurance of suffering, and of blessing those who would oppose them.

Neste trabalho faz-se o questionamento e a caracterização do executivo, buscando inicialmente observar como seu papel pode ser compreendido de uma perspectiva sociológica, tomando a Administração de Empresas como profissão e verificando a hipótese de se enquadrar o executivo como profissional. O cargo e a função do executivo são examinados sob o ângulo da burocracia, em sentido geral e no capitalismo, e são identificadas suas competências e condutas demandadas no atual estágio de racionalização das modernas organizações, mostrando que a atuação do executivo transcende o âmbito estritamente burocrático. A vocação do executivo, dimensão \"irracional\" como no sentido de paixão, é revelada em aparente contradição com seu lado racional de planejamento ou controle do negócio e da carreira - e também disso depende sua ascensão profissional. Por fim, revela-se o executivo como portador de um capitalismo, responsável pela continuidade de um sistema de dominação racionalmente legitimado e pela reprodução e expansão do capital, para o que não raro deve promover transformações em sua própria estrutura, a organização capitalista. Nesse sentido o executivo pode nos sinalizar um novo paradigma de profissional no capitalismo moderno. / This work questions and characterizes the executive, initially trying to understand his role under a sociological perspective and Business Administration as a profession to check the hypothesis of framing executive effectively as a professional. The executive function and position are examined by the viewpoint of burocracy, both in a general sense and in special in the capitalism. His competencies and conducts required in the modern organization present stage of rationalization, to reveal that he plays a role that is beyond the mere burocratic domain. The vocation of the executive, \"non rational\" dimension as in the sense of passion, is shown in apparent contradiction to his rational business and own career control and planning - this is also decisive in his professional progress. Finally, the executive is revealed as \"carrier\" of Capitalism, responsible for the continuity de a system of authority rationally legitimated and for the reproduction and growth of capital, for which sake he must eventually promote transformations in its own structure, the capitalist organization. In so far, the executive can point out to a new professional paradigm in contemporary Capitalism.

Com o desenvolvimento do sequenciamento em larga escala, novas tecnologias surgiram para auxiliar o estudo de sequências de ácidos nucleicos (DNA e cDNA); como consequência, o desenvolvimento de novas ferramentas para analisar o grande volume de dados gerados fez-se necessário. Entre essas novas tecnologias, uma, em particular, chamada Imunoprecipitação de Cromatina seguida de sequenciamento de DNA em larga escala ou CHIP-Seq, tem recebido muita atenção nos últimos anos. Esta tecnologia tornou-se um método usado amplamente para mapear sítios de ligação de proteínas de interesse no genoma. A análise de dados resultantes de experimentos de ChIP-Seq é desaadora porque o mapeamento das sequências no genoma apresenta diferentes formas de viés. Os métodos existentes usados para encontrar picos em dados de ChIP-Seq apresentam limitações relacionadas ao número de amostras de controle e tratamento usadas, e em relação à forma como essas amostras são combinadas. Nessa tese, mostramos que métodos baseados em testes estatísticos de hipótese tendem a encontrar um número muito maior de picos à medida que aumentamos o tamanho da amostra, o que os torna pouco conáveis para análise de um grande volume de dados. O presente estudo descreve um método estatístico Bayesiano, que utiliza meta-análise para encontrar sítios de ligação de proteínas de interesse no genoma resultante de experimentos de ChIPSeq. Esse métodos foi chamado Meta-Analysis Bayesian Approach ou MABayApp. Nós mostramos que o nosso método é robusto e pode ser utilizado com diferentes números de amostras de controle e tratamentos, assim como quando comparando amostras provenientes de diferentes tratamentos. / With the development of high-throughput sequencing, new technologies emerged for the study of nucleic acid sequences (DNA and cDNA) and as a consequence, the necessity for tools to analyse a great volume of data was made necessary. Among these new technologies, one in special Chromatin Immunoprecipitation followed by massive parallel DNA Sequencing, or ChIP-Seq, has been evidenced during the last years. This technology has become a widely used method to map locations of binding sites for a given protein in the genome. The analysis of data resulting from ChIP-Seq experiments is challenging since it can have dierent sources of bias during the sequencing and mapping of reads to the genome. Current methods used to nd peaks in this ChIP-Seq have limitations regarding the number of treatment and control samples used and on how these samples should be used together. In this thesis we show that since most of these methods are based on traditional statistical hypothesis tests, by increasing the sample size the number of peaks considered signicant changes considerably. This study describes a Bayesian statistical method using meta-analysis to discover binding sites of a protein of interest based on peaks of reads found in ChIP-Seq data. We call it Meta- Analysis Bayesian Approach or MABayApp. We show that our method is robust and can be used for dierent number of control and treatment samples, as well as when comparing samples under dierent treatments.

Retention in care is pivotal to preventing an AIDS diagnosis among people living with HIV. Poor adherence to scheduled primary care appointments is associated with negative health outcomes among HIV patients. The present study examined the impact of an automated appointment reminder system on primary medical care and behavioral health appointment attendance at an urban HIV clinic. The study employed data from appointments at NO/AIDS Task Force between January 15, 2012 and April 15, 2013. Appointments categorized as “attended” or “no show” during the study period were analyzed and findings suggested utilization of an automated appointment reminder system was associated with increased attendance to primary care and psychiatric appointments. Additional factors studied and found to be predictors of poor primary care and behavioral health appointment attendance were younger age and African American race. These findings suggest other urban HIV clinics should consider utilizing automated appointment reminder systems if their patient population has suitable phone access as it is an effective way to improve appointment adherence. / acase@tulane.edu