Linking cell dynamics with coexpression networks to characterize key events in chronic virus infection
- Autores: María Graciela Riera Domínguez
- Directores de la Tesis: Jordi Marquès Argilaguet (dir. tes.), Andreas Meyerhans (codir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2018
- Idioma: español
- Tribunal Calificador de la Tesis: Miguel Ángel Martínez de la Sierra (presid.), Cristina López Rodríguez (secret.), Juan Carlos Saíz Calahorra (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
- Materias:
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- Resumen
The host immune response against infection requires the coordinated action of many diverse cell subsets that dynamically adapt to a pathogen threat. Due to the complexity of such a response, most immunological studies have focused on a few genes, proteins, or cell types.
With the development of “omic”-technologies and computational analysis methods, attempts to analyze and understand complex system dynamics are now feasible. However, the decomposition of transcriptomic data sets generated from complete organs remains a major challenge. Here, we combined Weighted Gene Coexpression Network Analysis (WGCNA) and Digital Cell Quantifier (DCQ) to analyze time-resolved mouse splenic transcriptomes in acute and chronic Lymphocytic Choriomeningitis Virus (LCMV) infections. This enabled us to generate hypotheses about complex immune functioning after a virus-induced perturbation.
This strategy was validated by successfully predicting several known immune phenomena, such as effector cytotoxic T lymphocyte (CTL) expansion and exhaustion. Furthermore, we predicted and subsequently verified experimentally that virus-specific CD8+ T cells with an early effector transcriptome profile participate in the host adaptation to an overwhelming virus threat. Thus, the linking of gene expression changes with immune cell kinetics provides novel insights into the complex immune processes within infected tissues.
