Applied single-cell methods for basic and translational immunology
Abstract/Contents
- Abstract
- The immune system is a complex network of specialized cells that coordinate to eliminate immune challenges while minimally damaging self. Understanding the role of each cell in that network requires accurate quantification of informative biological features of single cells. Here, we innovated and applied single-cell methods and purpose- driven computational analyses to problems in basic and translational immunology. We developed a highly-multiplexed screen to quantify the co-expression of 351 surface molecules on millions of human B cells. We identified differentially expressed molecules and aligned their variance with isotype usage, VDJ sequence, metabolic profile, biosynthesis activity, and signaling response. Based on these analyses, we proposed a classification scheme to segregate B cells from four lymphoid tissues into twelve unique subsets, providing a framework for further investigations of human B cell identity and function. Additionally, we introduced morphometry, a high-throughput, quantitative, single-cell mass-cytometry-based assay that measures cell morphological features by their underlying molecular components. We applied multiplexed morphometric profiling and surface molecule immunophenotyping to 71 diverse clinical hematopathology samples and demonstrated that our approach was superior to flow cytometry and comparable to expert microscopy for tumor cell identification and enumeration. We introduced linear discriminant analysis (LDA) to generate morphometric maps that facilitate visualization and quantification of tumor cells. This contextualization of traditional surface markers on independent morphometric frameworks permits more sensitive and automated diagnosis of complex hematopoietic diseases.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Glass, David Richard |
|---|---|
| Degree supervisor | Bendall, Sean, 1979- |
| Thesis advisor | Bendall, Sean, 1979- |
| Thesis advisor | Boyd, Scott, 1970- |
| Thesis advisor | Mallick, Parag, 1976- |
| Thesis advisor | Pulendran, B. (Bali) |
| Degree committee member | Boyd, Scott, 1970- |
| Degree committee member | Mallick, Parag, 1976- |
| Degree committee member | Pulendran, B. (Bali) |
| Associated with | Stanford University, Program in Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | David Richard Glass. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/xt954yp7889 |
Access conditions
- Copyright
- © 2021 by David Richard Glass
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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