14 resultados para Genomic data integration


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Dissertação apresentada para obtenção do Grau de Doutor em Engenharia do Ambiente pela Universidade Nova de Lisboa,Faculdade de Ciências e Tecnologia

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Dissertação para obtenção do Grau de Mestre em Engenharia Informática

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Thesis submitted to Faculdade de Ciências e Tecnologia of the Universidade Nova de Lisboa, in partial fulfillment of the requirements for the degree of Master in Computer Science

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FEMS Yeast Research, Vol. 9, nº 4

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Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

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Cork stopper manufacturing process includes an operation, known as stabilisation, by which humid cork slabs are extensively colonised by fungi. The effects of fungal growth on cork are yet to be completely understood and are considered to be involved in the so called “cork taint” of bottled wine. It is essential to identify environmental constraints which define the appearance of the colonising fungal species and to trace their origin to the forest and/or as residents in the manufacturing space. The present article correlates two sets of data, from consecutive years and the same season, of systematic biologic sampling of two manufacturing units, located in the North and South of Portugal. Chrysonilia sitophila dominance was identified, followed by a high diversity of Penicillium species. Penicillium glabrum, found in all samples, was the most frequent isolated species. P. glabrum intra-species variability was investigated using DNA fingerprinting techniques revealing highly discriminative polymorphic markers in the genome. Cluster analysis of P. glabrum data was discussed in relation to the geographical location of strains, and results suggest that P. glabrum arise from predominantly the manufacturing space, although cork resident fungi can also contrib

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RESUMO: Introdução: A espondilite anquilosante (EA) é uma doença inflamatória crónica caracterizada pela inflamação das articulações sacroilíacas e da coluna. A anquilose progressiva motiva uma deterioração gradual da função física e da qualidade de vida. O diagnóstico e o tratamento precoces podem contribuir para um melhor prognóstico. Neste contexto, a identificação de biomarcadores, assume-se como sendo muito útil para a prática clínica e representa hoje um grande desafio para a comunidade científica. Objetivos: Este estudo teve como objetivos: 1 - caracterizar a EA em Portugal; 2 - investigar possíveis associações entre genes, MHC e não-MHC, com a suscetibilidade e as características fenotípicas da EA; 3 - identificar genes candidatos associados a EA através da tecnologia de microarray. Material e Métodos: Foram recrutados doentes com EA, de acordo com os critérios modificados de Nova Iorque, nas consultas de Reumatologia dos diferentes hospitais participantes. Colecionaram-se dados demográficos, clínicos e radiológicos e colhidas amostras de sangue periférico. Selecionaram-se de forma aleatória, doentes HLA-B27 positivos, os quais foram tipados em termos de HLA classe I e II por PCR-rSSOP. Os haplótipos HLA estendidos foram estimados pelo algoritmo Expectation Maximization com recurso ao software Arlequin v3.11. As variantes alélicas dos genes IL23R, ERAP1 e ANKH foram estudadas através de ensaios de discriminação alélica TaqMan. A análise de associação foi realizada utilizando testes da Cochrane-Armitage e de regressão linear, tal como implementado pelo PLINK, para variáveis qualitativas e quantitativas, respetivamente. O estudo de expressão génica foi realizado por Illumina HT-12 Whole-Genome Expression BeadChips. Os genes candidatos foram validados usando qPCR-based TaqMan Low Density Arrays (TLDAs). Resultados: Foram incluídos 369 doentes (62,3% do sexo masculino, com idade média de 45,4 ± 13,2 anos, duração média da doença de 11,4 ± 10,5 anos). No momento da avaliação, 49,9% tinham doença axial, 2,4% periférica, 40,9% mista e 7,1% entesopática. A uveíte anterior aguda (33,6%) foi a manifestação extra-articular mais comum. Foram positivos para o HLA-B27, 80,3% dos doentes. Os haplótipo A*02/B*27/Cw*02/DRB1*01/DQB1*05 parece conferir suscetibilidade para a EA, e o A*02/B*27/Cw*01/DRB1*08/DQB1*04 parece conferir proteção em termos de atividade, repercussão funcional e radiológica da doença. Três variantes (2 para IL23R e 1 para ERAP1) mostraram significativa associação com a doença, confirmando a associação destes genes com a EA na população Portuguesa. O mesmo não se verificou com as variantes estudadas do ANKH. Não se verificou associação entre as variantes génicas não-MHC e as manifestações clínicas da EA. Foi identificado um perfil de expressão génica para a EA, tendo sido validados catorze genes - alguns têm um papel bem documentado em termos de inflamação, outros no metabolismo da cartilagem e do osso. Conclusões: Foi estabelecido um perfil demográfico e clínico dos doentes com EA em Portugal. A identificação de variantes génicas e de um perfil de expressão contribuem para uma melhor compreensão da sua fisiopatologia e podem ser úteis para estabelecer modelos com relevância em termos de diagnóstico, prognóstico e orientação terapêutica dos doentes. -----------ABSTRACT: Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder characterized by inflammation in the spine and sacroiliac joints leading to progressive joint ankylosis and in progressive deterioration of physical function and quality of life. An early diagnosis and early therapy may contribute to a better prognosis. The identification of biomarkers would be helpful and represents a great challenge for the scientific community. Objectives: The present study had the following aims: 1- to characterize the pattern of AS in Portuguese patients; 2- to investigate MHC and non-MHC gene associations with susceptibility and phenotypic features of AS and; 3- to identify candidate genes associated with AS by means of whole-genome microarray. Material and Methods: AS was defined in accordance to the modified New York criteria and AS cases were recruited from hospital outcares patient clinics. Demographic and clinical data were recorded and blood samples collected. A random group of HLA-B27 positive patients and controls were selected and typed for HLA class I and II by PCR-rSSOP. The extended HLA haplotypes were estimated by Expectation Maximization Algorithm using Arlequin v3.11 software. Genotyping of IL23R, ERAP1 and ANKH allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests as implemented in PLINK, for dichotomous and quantitative variables, respectively. Gene expression profile was carried out using Illumina HT-12 Whole-Genome Expression BeadChips and candidate genes were validated using qPCR-based TaqMan Low Density Arrays (TLDAs). Results: A total of 369 patients (62.3% male; mean age 45.4±13.2 years; mean disease duration 11.4±10.5 years), were included. Regarding clinical disease pattern, at the time of assessment, 49.9% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopathic disease. Acute anterior uveitis (33.6%) was the most common extra-articular manifestation. 80.3% of AS patients were HLA-B27 positive. The haplotype A*02/B*27/Cw*02/DRB1*01/DQB1*05 seems to confer susceptibility to AS, whereas A*02/B*27/Cw*01/DRB1*08/DQB1*04 seems to provide protection in terms of disease activity, functional and radiological repercussion. Three markers (two for IL23R and one for ERAP1) showed significant single-locus disease associations. Association of these genes with AS in the Portuguese population was confirmed, whereas ANKH markers studied did not show an association with AS. No association was seen between non-MHC genes and clinical manifestations of AS. A gene expression signature for AS was established; among the fourteen validated genes, a number of them have a well-documented inflammatory role or in modulation of cartilage and bone metabolism. Conclusions: A demographic and clinical profile of patients with AS in Portugal was established. Identification of genetic variants of target genes as well as gene expression signatures could provide a better understanding of AS pathophysiology and could be useful to establish models with relevance in terms of susceptibility, prognosis, and potential therapeutic guidance.

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Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

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Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

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Dissertação para obtenção do Grau de Mestre em Engenharia Informática

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In the last few years, we have observed an exponential increasing of the information systems, and parking information is one more example of them. The needs of obtaining reliable and updated information of parking slots availability are very important in the goal of traffic reduction. Also parking slot prediction is a new topic that has already started to be applied. San Francisco in America and Santander in Spain are examples of such projects carried out to obtain this kind of information. The aim of this thesis is the study and evaluation of methodologies for parking slot prediction and the integration in a web application, where all kind of users will be able to know the current parking status and also future status according to parking model predictions. The source of the data is ancillary in this work but it needs to be understood anyway to understand the parking behaviour. Actually, there are many modelling techniques used for this purpose such as time series analysis, decision trees, neural networks and clustering. In this work, the author explains the best techniques at this work, analyzes the result and points out the advantages and disadvantages of each one. The model will learn the periodic and seasonal patterns of the parking status behaviour, and with this knowledge it can predict future status values given a date. The data used comes from the Smart Park Ontinyent and it is about parking occupancy status together with timestamps and it is stored in a database. After data acquisition, data analysis and pre-processing was needed for model implementations. The first test done was with the boosting ensemble classifier, employed over a set of decision trees, created with C5.0 algorithm from a set of training samples, to assign a prediction value to each object. In addition to the predictions, this work has got measurements error that indicates the reliability of the outcome predictions being correct. The second test was done using the function fitting seasonal exponential smoothing tbats model. Finally as the last test, it has been tried a model that is actually a combination of the previous two models, just to see the result of this combination. The results were quite good for all of them, having error averages of 6.2, 6.6 and 5.4 in vacancies predictions for the three models respectively. This means from a parking of 47 places a 10% average error in parking slot predictions. This result could be even better with longer data available. In order to make this kind of information visible and reachable from everyone having a device with internet connection, a web application was made for this purpose. Beside the data displaying, this application also offers different functions to improve the task of searching for parking. The new functions, apart from parking prediction, were: - Park distances from user location. It provides all the distances to user current location to the different parks in the city. - Geocoding. The service for matching a literal description or an address to a concrete location. - Geolocation. The service for positioning the user. - Parking list panel. This is not a service neither a function, is just a better visualization and better handling of the information.

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RESUMO: A Nigéria tem uma população estimada em cerca de 170 milhões de pessoas. O número de profissionais de saúde mental é muito diminuto, contando apenas com 150 psiquiatras o que perfaz aproximadamente um rácio de psiquiatra: população de mais de 1:1 milhão de pessoas. O Plano Nacional de Saúde Mental de 1991 reconheceu esta insuficiência e recomendou a integração dos serviços de saúde mental nos cuidados de saúde primários (CSP). Depois de mais de duas décadas, essa política não foi ainda implementada. Este estudo teve como objetivos mapear a estrutura organizacional dos serviços de saúde mental da Nigéria, e explorar os desafios e barreiras que impedem a integração bem-sucedida dos serviços de saúde mental nos cuidados de saúde primários, isto segundo a perspectiva dos profissionais dos cuidados de saúde primários. Com este objetivo, desenvolveu-se um estudo exploratório sequencial e utilizou-se um modelo misto para a recolha de dados. A aplicação em simultâneo de abordagens qualitativas e quantitativas permitiram compreender os problemas relacionados com a integração dos serviços de saúde mental nos CSP na Nigéria. No estudo qualitativo inicial, foram realizadas entrevistas com listagens abertas a 30 profissionais dos CSP, seguidas de dois grupos focais com profissionais dos CSP de duas zonas governamentais do estado de Oyo de forma a obter uma visão global das perspectivas destes profissionais locais sobre os desafios e barreiras que impedem uma integração bem-sucedida dos serviços de saúde mental nos CSP. Subsequentemente, foram realizadas entrevistas com quatro pessoas-chave, especificamente coordenadores e especialistas em saúde mental. Os resultados do estudo qualitativo foram utilizados para desenvolver um questionário para análise quantitativa das opiniões de uma amostra maior e mais representativa dos profissionais dos CSP do Estado de Oyo, bem como de duas zonas governamentais locais do Estado de Osun. As barreiras mais comummente identificadas a partir deste estudo incluem o estigma e os preconceitos sobre a doença mental, a formação inadequada dos profissionais dos CPS sobre saúde mental, a perceção pela equipa dos CSP de baixa prioridade de ação do Governo, o medo da agressão e violência pela equipa dos CSP, bem como a falta de disponibilidade de fármacos. As recomendações para superar estes desafios incluem a melhoria sustentada dos esforços da advocacia à saúde mental que vise uma maior valorização e apoio governamental, a formação e treino organizados dos profissionais dos cuidados primários, a criação de redes de referência e de apoio com instituições terciárias adjacentes, e o engajamento da comunidade para melhorar o acesso aos serviços e à reabilitação, pelas pessoas com doença mental. Estes resultados fornecem indicações úteis sobre a perceção das barreiras para a integração bem sucedida dos serviços de saúde mental nos CSP, enquanto se recomenda uma abordagem holística e abrangente. Esta informação pode orientar as futuras tentativas de implementação da integração dos serviços de saúde mental nos cuidados primários na Nigéria.------------ABSTRACT: Nigeria has an estimated population of about 170 million people but the number of mental health professionals is very small, with about 150 psychiatrists. This roughly translates to a psychiatrist:population ratio of more than 1:1 million people. The National Mental Health Policy of 1991 recognized this deficiency and recommended the integration of mental health into primary health care (PHC) delivery system. After more than two decades, this policy has yet to be implemented. This study aimed to map out the organizational structure of the mental health systems in Nigeria, and to explore the challenges and barriers preventing the successful integration of mental health into primary health care, from the perspective of the primary health care workers. A mixed methods exploratory sequential study design was employed, which entails the use of sequential timing in the combined methods of data collection. A combination of qualitative and uantitative approaches in sequence, were utilized to understand the problems of mental health services integration into PHC in Nigeria. The initial qualitative phase utilized free listing interviews with 30 PHC workers, followed by two focus group discussions with primary care workers from two Local Government Areas (LGA) of Oyo State to gain useful insight into the local perspectives of PHC workers about the challenges and barriers preventing successful integration of mental health care services into PHC. Subsequently, 4 key informant interviews with PHC co-ordinators and mental health experts were carried out. The findings from the qualitative study were utilized to develop a quantitative study questionnaire to understand the opinions of a larger and more representative sample of PHC staff in two more LGAs of Oyo State, as well as 2 LGAs from Osun State. The common barriers identified from this study include stigma and misconceptions about mental illness, inadequate training of PHC staff about mental health, low government priority, fear of aggression and violence by the PHC staff, as well as non-availability of medications. Recommendations for overcoming these challenges include improved and sustained efforts at mental health advocacy to gain governmental attention and support, organized training and retraining for primary care staff, establishment of referral and supportive networks with neighbouring tertiary facilities and community engagement to improve service utilization and rehabilitation of mentally ill persons. These findings provide useful insight into the barriers to the successful integration of mental health into PHC, while recommending a holistic and comprehensive approach. This information can guide future attempts to implement the integration of mental health into primary care in Nigeria.