Using high-throughput genomics to open and understand new biological questions
Abstract/Contents
- Abstract
- High-throughput genomics has enabled the profiling of cells and cell states at previously unprecedented resolution. These genomic technologies include methods such as RNA-sequencing, which provides insight into the transcriptional state of cells, and ATAC-sequencing, which provides insight into the epigenetic chromatin state of cells. These methods can be performed at single-cell levels, providing a fine-grained look into heterogeneous tissues. In this dissertation, I describe the use of genomic technologies toward three areas of interest. First, using large-scale bulk RNA-sequencing datasets to computationally predict the transcriptional start site of a circular RNA, ciRS-7. This allowed the identification of the linear host RNA from which ciRS-7 is transcribed. Second, I describe the combining of single-cell ATAC-sequencing with CRISPR profiling in a new method, Perturb-ATAC. Perturb-ATAC allows the analysis of the regulatory landscape in single cells after a variety of CRISPR perturbations, allowing the linkage of transcriptional regulators to their epigenetic targets. Third, I apply single-cell RNA-sequencing analysis to understanding the clinical profile of CD19-directed CAR-T therapy. CD19-directed CAR-T has shown tremendous promise for the treatment of B cell malignancies, but also a high incidence of neurotoxicity, and through the use of single-cell analyses, I identify a CD19-positive population within the brain. These three applications of high-throughput genomics demonstrate the power of genomic analyses to understanding novel questions in biology, and individually resolve particular questions of interest while posing new questions for future work in their respective areas.
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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Parker, Kevin |
|---|---|
| Degree supervisor | Chang, Howard Y. (Howard Yuan-Hao), 1972- |
| Thesis advisor | Chang, Howard Y. (Howard Yuan-Hao), 1972- |
| Thesis advisor | Khavari, Paul A |
| Thesis advisor | Majeti, Ravindra, 1972- |
| Thesis advisor | Satpathy, Ansuman |
| Degree committee member | Khavari, Paul A |
| Degree committee member | Majeti, Ravindra, 1972- |
| Degree committee member | Satpathy, Ansuman |
| Associated with | Stanford University, Department of Stem Cell Biology and Regenerative Medicine |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kevin Parker. |
|---|---|
| Note | Submitted to the Department of Stem Cell Biology and Regenerative Medicine. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Kevin Parker
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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