Integração de estudos de associação genômica ampla de doenças crônicas com dados de sequenciamento de RNA de célula única (scRNAseq) do hipotálamo de humanos
Arquivos
Data
2024-12-06
Autores
Kim, Gloria Bada 
Orientadores
Mecawi, André de Souza
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
As doenças crônicas não transmissíveis (DCNT), como hipertensão arterial, depressão maior e obesidade, representam as principais causas de morbimortalidade global, afetando milhões de pessoas. Estas condições multifatoriais estão frequentemente relacionadas ao hipotálamo, uma região cerebral responsável pela regulação de diversos mecanismos fisiológicos, como controle de ritmo circadiano e respostas ao estresse, termorregulação, regulação de comportamentos reprodutivos, alimentares, de crescimento, entre outros. Este trabalho buscou compreender as vias fisiopatológicas subjacentes a essas doenças nos níveis celular e molecular por meio da integração de dados de estudos de associação genômica ampla (GWAS) destas três doenças com dados de sequenciamento de RNA de célula única (scRNAseq) do hipotálamo de camundongos, convertidos para os ortólogos humanos. Para essa análise, foi utilizada a ferramenta bioinformática MAGMA.Celltyping, empregando dados de transcriptoma de célula única em três níveis de clusterização celular: 7, 25 e 66 tipos celulares. Os resultados revelaram que genes com polimorfismos associados às DCNT analisadas podem estar enriquecidos mais ou menos convergentes nos diferentes tipos celulares hipotalâmicos, de acordo com o nível de clusterização utilizado. Além disso, desafios técnicos, como problemas de versionamento dos pacotes, foram identificados ao implementar outras ferramentas bioinformáticas, como CELLECT e sc-linker, que também integram dados de GWAS e de scRNAseq.
Non-communicable chronic diseases (NCDs), including hypertension, major depression, and obesity, rank among the leading global causes of morbidity and mortality, affecting millions worldwide. These multifactorial conditions are often linked to the hypothalamus, a brain region crucial for regulating various physiological processes. The hypothalamus plays a central role in circadian rhythm control, stress responses, thermoregulation, and behaviors related to reproduction, feeding, and growth, among others. This study aimed to investigate the underlying pathophysiological pathways of these diseases at the cellular and molecular levels. For this purpose, genome-wide association study (GWAS) data for the three diseases were integrated with single-cell RNA sequencing (scRNAseq) data from the hypothalamus of mice, converted to their human orthologs. The bioinformatics tool MAGMA.Celltyping was used to perform this integration. Single-cell transcriptomic data were analyzed at three levels of cellular clustering: 7, 25, and 66 cell types. The results revealed that genes with polymorphisms associated with the analyzed NCDs may show differential enrichment and convergence across hypothalamic cell types, depending on the clustering level applied. In addition, technical challenges were encountered during the implementation of other bioinformatics tools, such as CELLECT and sc-linker, which also integrate GWAS and scRNAseq data. One notable issue was package versioning, which impacted the usability of these tools. This work provides insights into the cellular and molecular mechanisms linking NCDs to the hypothalamus and highlights the potential of integrative approaches in unraveling disease-related pathways.
Non-communicable chronic diseases (NCDs), including hypertension, major depression, and obesity, rank among the leading global causes of morbidity and mortality, affecting millions worldwide. These multifactorial conditions are often linked to the hypothalamus, a brain region crucial for regulating various physiological processes. The hypothalamus plays a central role in circadian rhythm control, stress responses, thermoregulation, and behaviors related to reproduction, feeding, and growth, among others. This study aimed to investigate the underlying pathophysiological pathways of these diseases at the cellular and molecular levels. For this purpose, genome-wide association study (GWAS) data for the three diseases were integrated with single-cell RNA sequencing (scRNAseq) data from the hypothalamus of mice, converted to their human orthologs. The bioinformatics tool MAGMA.Celltyping was used to perform this integration. Single-cell transcriptomic data were analyzed at three levels of cellular clustering: 7, 25, and 66 cell types. The results revealed that genes with polymorphisms associated with the analyzed NCDs may show differential enrichment and convergence across hypothalamic cell types, depending on the clustering level applied. In addition, technical challenges were encountered during the implementation of other bioinformatics tools, such as CELLECT and sc-linker, which also integrate GWAS and scRNAseq data. One notable issue was package versioning, which impacted the usability of these tools. This work provides insights into the cellular and molecular mechanisms linking NCDs to the hypothalamus and highlights the potential of integrative approaches in unraveling disease-related pathways.
Descrição
Citação
KIM, Gloria Bada. Integração de estudos de associação genômica ampla de doenças crônicas com dados de sequenciamento de RNA de célula única (scRNAseq) do hipotálamo de humanos. 2024. 76 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.
ODS
Não se aplica