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Statistical analysis of longitudinal RBC omics data

2025Dissertação de mestrado Acesso aberto
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dc.contributor.authorSilva, Carolina Simões Gonçalves
dc.contributor.institutionFaculty of Sciences
dc.contributor.institutionDepartment of Statistics and Operational Research
dc.contributor.supervisorAntunes, Marília Cristina de Sousa
dc.contributor.supervisorPenque, Deborah
dc.date.accessioned2026-01-06T16:15:01Z
dc.date.available2026-01-06T16:15:01Z
dc.date.issued2025
dc.descriptionTese de Mestrado, Bioestatística, 2025, Universidade de Lisboa, Faculdade de Ciências
dc.description.abstractRed blood cells (RBCs) are emerging as important modulators of the immune system. Despite evidence that alterations in RBC functionality are associated with disease severity in COVID-19 patients, there is no information regarding the impact of RBC activity on the immune response to COVID-19 vaccination. This work aims to establish an adequate methodology for the statistical analysis of longitudinal RBC metabolomics data collected during COVID-19 vaccination (n=22, 5 time points) to identify metabolites with significant changes throughout the immunization process. For the pre-treatment of the metabolomics data set, different pre-treatment methodologies comprised of imputation and normalization steps were compared to investigate which algorithm and application order was more adequate. Testing of these methods showed that normalization followed by kNN imputation using cosine distance was highlighted as the best-performing pre-treatment strategy. Following its application, generalized estimating equations (GEEs) created from the normalized data led to the identification of 30 metabolites with significant changes in concentration between different time points of COVID-19 vaccination. Significant RBC metabolites were linked to major metabolic pathways in the cells, such as the metabolism of amino acids and purines, and the transport of small molecules through the cellular membrane. Some of these metabolites were discovered to have relevant functions in the development of an effective immune response against infections, like COVID-19. The connections between these metabolites and the defense mechanisms commonly used by cells to fight viral infections offer a strong clue for the immune functions that those metabolites may have in the human body, suggesting that the RBC metabolism could play a significant part in the generation of an immune response to COVID-19 vaccination. Further work is in progress to integrate and correlate proteomic data retrieved from the same longitudinal experiment for a comprehensive depiction of the RBC function in the COVID-19 vaccine-induced immunization process.en
dc.formatapplication/pdf
dc.identifier.tid204121795
dc.identifier.urihttp://hdl.handle.net/10400.5/116491
dc.language.isoeng
dc.subjectCOVID-19 vaccination
dc.subjectImmune response
dc.subjectLongitudinal data
dc.subjectMetabolomic analysis
dc.subjectRed blood cells
dc.titleStatistical analysis of longitudinal RBC omics dataen
dc.typemaster thesis
dspace.entity.typePublication
rcaap.rightsopenAccess

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