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Sub-phenotypes of Macrophages and Monocytes in COPD and Molecular Pathways for Novel Drug Discovery

Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder and the third leading cause of mortality. In this thesis we performed a clustering analysis of four specific immune cells in the GSE136831 dataset, using the default recommended parameters of the Seurat package in R, and obtained 16 subclasses with various COPD and cell-type proportions. Clusters 3, 7 and 9 had more pronounced independence and were all composed of macrophage-dominated control samples. The results of the pseudo-time analysis based on Monocle 3 package in R showed three different patterns of cell evolution. All started with a high percentage of COPD states, one ended with a high rate of Control states, and the other two still finished with a high percentage of COPD states. The results of differentially expressed gene analysis corroborated the existence of finer clusters and provided support for their rational categorization based on the similar marker genes. The gene ontology (GO) enrichment analysis for cluster 0 and cluster 6 provided feedback on enriched biological process terms with significant and unique characteristics, which could help explore latent novel COPD treatment directions. Finally, some top-ranked potential pharmaceutical molecules were searched via the connectivity map (cMAP) database. / Graduate / 2023-08-12

Identiferoai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/14119
Date22 August 2022
CreatorsYan, Yichen
ContributorsZhang, Xuekui
Source SetsUniversity of Victoria
LanguageEnglish, English
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf
RightsAvailable to the World Wide Web

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