It is increasingly recognized that in order to gain further insights into human disorders and develop new therapeutic strategies and diagnostic tools, it is critical to have a comprehensive... Show moreIt is increasingly recognized that in order to gain further insights into human disorders and develop new therapeutic strategies and diagnostic tools, it is critical to have a comprehensive overview of immune cell subsets resident in tissues under physiological and pathological conditions. Flow cytometry has been the golden standard for analyzing immune cell subsets, and with a typical experiment, dozens of immune subsets can be discriminated. Due to the lack of spectrally-resolvable fluorochromes, mass cytometry utilizing metal-conjugated antibodies has shown to be a powerful tool for dissecting the immune landscape even further. Inflammatory intestinal diseases can only be understood by studying specialized cell types within the tissue niche itself. In this thesis, we applied mass cytometry and data-driven, automated analysis approaches to investigate the complex compositions of heterogeneous cell subsets, such as those encountered in intestinal biopsies. These types of data have the potential to greatly improve our understanding of human disease. In concert with clinical data, mass cytometry could enable a finer classification of patients and might aid in the development of improved diagnostics, prognostics and personalized therapeutic regimens. Show less
In this dissertation we developed a number of automatic methods for multi-modal data registration, mainly between mass spectrometry imaging, imaging microscopy, and the Allen Brain Atlas. We... Show moreIn this dissertation we developed a number of automatic methods for multi-modal data registration, mainly between mass spectrometry imaging, imaging microscopy, and the Allen Brain Atlas. We have shown the importance of these methods for performing large scale preclinical biomarker discovery investigations for neurological disorders. We have also proposed a data-driven approach to stratify patients’ tumor tissues into molecularly distinct tumor subpopulations and automatically identify those tumor subpopulations that drive patient outcome. Show less
