Methods for inferring nucleosome positioning and transcription factor binding
Abstract/Contents
- Abstract
- Transcription factors bind DNA and regulate the expression of genes, thereby controlling cellular identity and differentiation. Where transcription factors bind is partially determined by DNA sequence, but is also influenced by chromatin architecture, with most transcription factors predominantly binding accessible, nucleosome-free DNA. Inferring when and where transcription factors bind is crucial for understanding how gene regulation is controlled during key cellular transitions. The Assay for Transpose Accessible Chromatin with high throughput sequencing (ATAC-seq) enables profiling of chromatin accessibility genome-wide and provides information about both nucleosome positioning and transcription factor binding within accessible regions of the genome. This work describes an algorithm for using ATAC-seq fragment size and position information to infer nucleosome positioning at high resolution within regulatory regions, as well as an extension of that algorithm for the inference of transcription factor binding. Recently, the ATAC-seq method was also adapted for application to single cells. While single-cell ATAC-seq can be used to probe heterogeneity in chromatin accessibility within populations, the resulting data is very sparse, presenting significant analytic challenges. This work also describes a method for using single cell or other sparse chromatin accessibility data to infer transcription factors associated with accessibility variation in single cells. The algorithms described in this work enable characterization of nucleosome positioning and transcription factor binding at high positional resolution using bulk, deeply sequenced data or characterization of transcription factor associated accessibility at single cell resolution using extremely sparse data. As studies continue to probe how cells differentiate or transition from one state to another, such interpretable analytic tools will be crucial for understanding how transcription factors and chromatin architecture mediate these complex processes.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Schep, Alicia |
|---|---|
| Associated with | Stanford University, Department of Genetics. |
| Primary advisor | Greenleaf, William James |
| Thesis advisor | Greenleaf, William James |
| Thesis advisor | Kundaje, Anshul, 1980- |
| Thesis advisor | Pritchard, Jonathan D |
| Thesis advisor | Steinmetz, Lars |
| Advisor | Kundaje, Anshul, 1980- |
| Advisor | Pritchard, Jonathan D |
| Advisor | Steinmetz, Lars |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Alicia Schep. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Alicia Nathalie Schep
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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