Beyond enhancer-promoter contact : leveraging deep learning to connect super-resolution DNA traces to transcription
Abstract/Contents
- Abstract
- Chromatin architecture plays an important role in gene regulation. Recent advances in super-resolution microscopy have made it possible to measure chromatin 3D structure and transcription in thousands of single cells. However, leveraging these complex datasets with a computationally unbiased method has not been achieved. In this dissertation, I present a deep learning-based approach to better understand to what degree chromatin structure relates to the transcriptional state of individual cells. Furthermore, I explore methods to "unpack the black box" to determine in an unbiased manner which structural features of chromatin regulation are most important for gene expression state. I apply this approach to the Optical Reconstruction of Chromatin Architecture dataset of the Bithorax gene cluster in Drosophila and show it significantly outperforms previous contact-focused methods. This work finds the structural information is distributed across the domain, overlapping and extending beyond domains identified by prior genetic analyses. Individual enhancer-promoter interactions are a minor contributor to predictions of activity.
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 | Rajpurkar, Aparna Rajiv |
|---|---|
| Degree supervisor | Boettiger, Alistair |
| Thesis advisor | Boettiger, Alistair |
| Thesis advisor | Bhatt, Ami (Ami Siddharth) |
| Thesis advisor | Kundaje, Anshul, 1980- |
| Thesis advisor | Winslow, Monte |
| Degree committee member | Bhatt, Ami (Ami Siddharth) |
| Degree committee member | Kundaje, Anshul, 1980- |
| Degree committee member | Winslow, Monte |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Aparna Rajiv Rajpurkar. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2021 by Aparna Rajiv Rajpurkar
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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