Princeton University Library Catalog
- Author/Artist:
- Boix, Carles [Browse]
- Format:
- Senior thesis
- Language:
- English
- Advisor(s):
- Storey, John [Browse]
- Department:
- Princeton University. Department of Molecular Biology [Browse]
- Class year:
- 2015
- Description:
- 107 pages
- Summary note:
- Characterizing the impact of changes in chromatin accessibility on gene expression is
essential to both obtaining an understanding of how gene mis-regulation leads to disease
and predicting the effects of non-coding mutations. We continue the work presented in
Marstrand & Storey (2014) identifying genes showing cell-specific concordance between
expression and chromatin accessibility among 20 cell lines using the angle ratio statistic
(ARS), a novel statistic developed to detect concordant outliers between two datasets. This
paper extends the analysis to 126 cell lines and reworks the generation of null statistics for
the ARS method. Our work proposes several extensions to the ARS method which use redundant
cell lines to increase the power to detect associations in these groups. We find that
enriched GO terms for significant genes called by ARS match cell line function and demonstrate
that correlated ARS lines correspond to biological groupings. Finally, we identify
local regions which significantly contribute to expression and chromatin accessibility concordance
and report transcription factor binding sites that are over and under represented
in these sequences. The ARS statistical framework can be extended to multiple dimensions
to incorporate additional genome-wide measurements of chromatin accessibility, applied
to alternative splicing instead of expression, or used to evaluate potential enhancers.
