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UBC Theses and Dissertations

Prediction of graft-versus-host disease based on supervised temporal analysis on high-throughput flow cytometry data Lee, Shang-Jung


Despite recent advancements in human immune-genetics, graft-versus-host disease (GvHD) continues to be the major and potentially fatal complication of hematopoietic stem cell transplantations affecting up to 80% of transplant patients [1]. Very little is known regarding the pathophysiologic mechanisms behind the manifestation of either acute or chronic GvHD. Diagnosis and treatment assessment are often hindered as they rely primarily on ambiguous clinical symptoms, such as tissue inflammation. It is likely that the outcome for patients diagnosed with GvHD could be improved if they were treated in a pre-emptive fashion, before the development of full-scale clinical symptoms. Using flow cytometry high content screening [2], 123 subsets of immune cells were identified from blood samples taken at multiple time points from 31 patients who underwent allogenic bone marrow transplantations. I assembled a novel analysis pipeline specifically designed to process this high-throughput clinical flow cytometry dataset. The pipeline included a novel quality assurance test [3] and temporal classification via functional linear discriminant analysis [4]. Temporal patterns of multiple immune cell abundances both after the transplantation and around the acute GvHD diagnosis were screened for potential discriminative power for either acute or chronic GvHD. Among many potential discriminative patterns: higher proportion values in immune cell with CD3⁺CD4⁺CD8β⁺ phenotype were found in acute GvHD patients (21), compared to the patients unaffected by GvHD (3), between zero and 120 days post-transplant. I also generated a list of recommendations for an extended study designed to validate the current findings. The global approach of the highthroughput flow cytometry technique and the novel temporal analysis pipeline, implemented according to the list of recommendations would be beneficial in elucidating pathophysiologic mechanisms of complex immunologically based diseases including GvHD.

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