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Tratamento de dados de NGS para pesquisa de novas mutações associadas à miocardiopatia hipertrófica
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Resumo(s)
A Sequenciação de Nova Geração (NGS - Next Generation Sequencing) está a revolucionar a investigação na área da biomédica, contribuindo significativamente para o avanço da medicina personalizada. A NGS, apoiando-se nos conhecimentos da Estatística Bayesiana e da Bioinformática para a análise e tratamento dos dados que esta técnica origina, torna-se num excelente exemplo dos novos campos multidisciplinares emergentes da Ciência. As novas potencialidades da NGS que a tornam tão atractiva para tantos novos projectos de investigação são a sua capacidade de misturar diversas amostras numa só leitura, com recurso a um sistema de código de barras, diminuindo custos e aumentando a rapidez da obtenção das amostras. Com o intuito de descobrir potenciais novas mutações associadas à Miocardiopatia Hipertrófica, estudou-se uma coorte de indivíduos que possuiam o diagnóstico clínico da doença, mas que, no entanto, não apresentavam qualquer mutação exónica patogénica. Tornam-se claras as vantagens desta nova metodologia, pois trazendo mais rapidez e permitindo uma análise a um maior número de genes, com custos reduzidos, torna possível a análise de todos os genes com associação conhecida e descrita na literatura. Neste projecto, obtiveram-se resultados positivos em relação a muitos genes já conhecidos que pela sequenciação padrão não tinham sido sequenciados ou detectados. A NGS demonstrou ter todo o potencial para tornar-se o novo método padrão de diagnóstico, sendo, por isso, necessário continuar aperfeiçoar e a melhorar a metodologias de tratamento e análise de dados provenientes desta nova técnica. Foram descobertos sete genes (CAV3, GLA, LDB3, MYLK2, MYOZ2, PRKAG2 e VCL) que ainda não foram oficialmente associados à patologia, sendo que na literatura apenas são referidas mutações a nível exónico. Apenas o gene ANKRD1 detectado com alterações já foi descrito com mutações exónicas e intrónicas. O gene CAV3 surge como associado à doença oficialmente em 2010, num artigo de revisão.
The Next-Generation Sequencing (NGS) is revolutionizing biomedical research, signi ficantly contributing to the enrichment of health sciences' field, inclusively towards a personalized medicine. NGS takes advantage of Bayesian Statistics and Bioinformatics knowledge, in order to analyse and process data, which is originated by this technique. NGS is an excellent example of the new multidisciplinary fields of Sciences. The innovative NGS's features, which make this technique so attractive for so many different research projects , are the possibility of mix several samples in just one read, using an associated barcode, which can reduce costs. Obtaining samples is quicker than with the standard method. With the purpose of discover unknown mutations associated with Hypertrophic Cardiomyopathy, we studied a group of individuals, which, in spite of presenting the disease's symptoms, did not have any pathogenic exonic mutation with the standard method of sequentiation. The advantages of this new methodology are quite clear. Accomplishing faster results and allowing analysis of a larger number of genes, with reduced costs, which allows to diagnose the patient concerning all genes described in the literature. In this project, we obtained positive results for many genes already known that were not sequenced or not detected by standard sequencing method. The NGS shown to have the necessary potential to become the new standard diagnostic method, and is therefore imperative to further re- fine and improve methods of treatment and analysis of data originated by this technique. In our project, we found seven genes (CAV3, GLA, LDB3, MYLK2, MYOZ2, PRKAG2 and VCL) which were not officially associated with the disease yet and in the literature only exonic mutations were described. Only ANKRD1 gene was detected with both exonic and intronic mutations. CAV3 gene appears in 2010 as officially associated with thedisease, in a review article.
The Next-Generation Sequencing (NGS) is revolutionizing biomedical research, signi ficantly contributing to the enrichment of health sciences' field, inclusively towards a personalized medicine. NGS takes advantage of Bayesian Statistics and Bioinformatics knowledge, in order to analyse and process data, which is originated by this technique. NGS is an excellent example of the new multidisciplinary fields of Sciences. The innovative NGS's features, which make this technique so attractive for so many different research projects , are the possibility of mix several samples in just one read, using an associated barcode, which can reduce costs. Obtaining samples is quicker than with the standard method. With the purpose of discover unknown mutations associated with Hypertrophic Cardiomyopathy, we studied a group of individuals, which, in spite of presenting the disease's symptoms, did not have any pathogenic exonic mutation with the standard method of sequentiation. The advantages of this new methodology are quite clear. Accomplishing faster results and allowing analysis of a larger number of genes, with reduced costs, which allows to diagnose the patient concerning all genes described in the literature. In this project, we obtained positive results for many genes already known that were not sequenced or not detected by standard sequencing method. The NGS shown to have the necessary potential to become the new standard diagnostic method, and is therefore imperative to further re- fine and improve methods of treatment and analysis of data originated by this technique. In our project, we found seven genes (CAV3, GLA, LDB3, MYLK2, MYOZ2, PRKAG2 and VCL) which were not officially associated with the disease yet and in the literature only exonic mutations were described. Only ANKRD1 gene was detected with both exonic and intronic mutations. CAV3 gene appears in 2010 as officially associated with thedisease, in a review article.
Descrição
Tese de mestrado em Bioestatística, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2012
Palavras-chave
Sequenciação de nova geração Estatística Bayesiana Bioinformática Miocardiopatia hipertrófica Teses de mestrado - 2012