Aplicación de la biología de sistemas al estudio de la malaria y búsqueda de biomarcadores y dianas terapéuticas

The purpose of this work is to apply systems biology tools to investigate the mechanisms involved in malaria parasite infection and identify potential biomarkers and therapeutic targets. We have started from a time series of microarray data of the spleen of mice infected with two strains of the para...

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Detalles Bibliográficos
Autor: Ferrer Almirall, Mireia
Tipo de recurso: tesis de maestría
Fecha de publicación:2019
País:España
Institución:Universitat Oberta de Catalunya (UOC)
Repositorio:O2, repositorio institucional de la UOC
OAI Identifier:oai:openaccess.uoc.edu:10609/91428
Acceso en línea:http://hdl.handle.net/10609/91428
Access Level:acceso abierto
Palabra clave:malaria
systems biology
therapeutic target
diana terapéutica
biología de sistemas
diana terapèutica
biologia de sistemes
malària
Biopharmaceutics -- TFM
Biofarmàcia -- TFM
Biofarmacia -- TFM
Descripción
Sumario:The purpose of this work is to apply systems biology tools to investigate the mechanisms involved in malaria parasite infection and identify potential biomarkers and therapeutic targets. We have started from a time series of microarray data of the spleen of mice infected with two strains of the parasite (NL and L) to determine the genes that are differentially expressed (DEG) with respect to control mice. From the DEG lists obtained, systems biology tools have been used in combination with biological significance analyses to obtain an integrated view of the biological processes that are altered in the disease and to identify possible biomarkers/therapeutic targets. To this end, the protein-protein interaction networks of the DEG have been modeled and the highly interconnected modules have been identified as possible functional units. DEG have also been characterized based on their temporal expression pattern to discover coregulated modules and characterize the processes involved in the different post-infection days. On the other hand, topological analyzes have been carried out to determine the most influential DEG of the network and of the different modules analyzed, obtaining a list of possible candidates for therapeutic targets. Finally, a druggability analysis has been carried out to validate the list of candidates obtained. Together, these analyzes offer an integrated view of the biological processes that determine the course of the disease, beyond the individual genes, as well as the identification of possible therapeutic targets and biomarkers of the disease.