Methods and models of screening genomic variants
Genomes are the basis of human biology and human disease. Understanding the role of each gene on a healthy or diseased phenotype requires an intervention to causally link between genotype and phenotype. Advances in RNA-guided endonucleases have enabled such pooled screens in human cells. I first con...
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| Format: | Thesis |
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Massachusetts Institute of Technology
2023
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| Online Access: | https://hdl.handle.net/1721.1/152824 |
| _version_ | 1826194175829213184 |
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| author | Frangieh, Chris J. |
| author2 | Zhang, Feng |
| author_facet | Zhang, Feng Frangieh, Chris J. |
| author_sort | Frangieh, Chris J. |
| collection | MIT |
| description | Genomes are the basis of human biology and human disease. Understanding the role of each gene on a healthy or diseased phenotype requires an intervention to causally link between genotype and phenotype. Advances in RNA-guided endonucleases have enabled such pooled screens in human cells. I first consider a model to understand drivers of immune evasion in a pooled knockout screen conducted in an in vitro model of metastatic melanoma. Next, I discuss strategies for scaling these screens to encompass a larger set of genes from the human genome. Finally, I explore how next-generation genome editors can move beyond knockout screens to identify the biological role of any sequence at any location in the human genome. |
| first_indexed | 2024-09-23T09:52:07Z |
| format | Thesis |
| id | mit-1721.1/152824 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:52:07Z |
| publishDate | 2023 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1528242023-11-03T03:54:13Z Methods and models of screening genomic variants Frangieh, Chris J. Zhang, Feng Regev, Aviv Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Genomes are the basis of human biology and human disease. Understanding the role of each gene on a healthy or diseased phenotype requires an intervention to causally link between genotype and phenotype. Advances in RNA-guided endonucleases have enabled such pooled screens in human cells. I first consider a model to understand drivers of immune evasion in a pooled knockout screen conducted in an in vitro model of metastatic melanoma. Next, I discuss strategies for scaling these screens to encompass a larger set of genes from the human genome. Finally, I explore how next-generation genome editors can move beyond knockout screens to identify the biological role of any sequence at any location in the human genome. Ph.D. 2023-11-02T20:19:08Z 2023-11-02T20:19:08Z 2023-09 2023-09-21T14:26:27.029Z Thesis https://hdl.handle.net/1721.1/152824 In Copyright - Educational Use Permitted Copyright retained by author(s) https://rightsstatements.org/page/InC-EDU/1.0/ application/pdf Massachusetts Institute of Technology |
| spellingShingle | Frangieh, Chris J. Methods and models of screening genomic variants |
| title | Methods and models of screening genomic variants |
| title_full | Methods and models of screening genomic variants |
| title_fullStr | Methods and models of screening genomic variants |
| title_full_unstemmed | Methods and models of screening genomic variants |
| title_short | Methods and models of screening genomic variants |
| title_sort | methods and models of screening genomic variants |
| url | https://hdl.handle.net/1721.1/152824 |
| work_keys_str_mv | AT frangiehchrisj methodsandmodelsofscreeninggenomicvariants |