Thursday, September 29, 2016

BISTRO - Laura Seaman

4:00 PM

2036 Palmer Commons

"High-resolution mapping of chromosomal aberrations in the colorectal cancer nucleome by chromosome conformation capture and gene expression"

BISTRO is restricted to U-M Bioinformatics Graduate Program students and faculty.


Chromosomal translocations and aneuploidy are hallmarks of cancer genomes. The impact of these genomic aberrations on structure-function relationships in the cancer genome, i.e. the cancer nucleome, is not yet understood. We analyze the nucleome of the colorectal cancer cell line HT-29 using chromosome conformation capture (Hi-C) to study genome structure complemented with RNA-seq to determine consequent changes in the transcriptome. We observe that translocations and copy number changes can be identified at high resolution from Hi-C data and the structure-function relationship present in normal cells is maintained in cancer. We introduce an entropy-based quantification of chromatin conformation to analyze the impact of chromosomal aberrations on the genomic stability of the region and its relationship to transcription. Using this method, we show translocations result in an increase in the correlation between gene expression and chromatin organization. Additionally, the homogeneously staining region (HSR) of HT-29, which includes the MYC oncogene, is positioned stochastically in different nuclei, interacting with various loci throughout the genome. Our methods can be applied to the assessment of the nucleome in many cell types.