chromosomal-instability

Chromosomal Instability Analysis

This analysis evaluates chromosomal instability by calculating chromosomal break point density calculations and circular plot visualization using CNV and SV data.

Table of Contents generated with DocToc

• Usage
• Methods and Output
• Summary of Custom Functions

Usage

This analysis can be run via the command line from the top directory of the repository as follows:

bash analyses/chromosome-instability/run_breakpoint_analysis.sh

Methods and Output

• 00-setup-breakpoint-data.R CNV and SV data are transformed into single breakpoint data as well as their intersection. These three datasets (intersection, CNV, and SV) are used to calculate genome wide breakpoint densities for each sample which are saved to three _breaks_densities.tsv files. Note that this script is set up to handle WXS and WGS separately, however currently our PBTA dataset only has CNV and SV data for WGS samples. Additionally, a breakpoint-data/breaks_lists.RDS file is saved which contains three data.frames:

1. intersection_of_breaks contains the intersection break counts for both SV and CNV break data.
2. cnv_breaks contains the number of break counts for CNV.
3. sv_breaks contains the number of break counts for SV.

• 01-localization-of-breakpoints.Rmd uses the data in breaks_lists.RDS to co-localize and map breakpoints by bins across the genome. These binned breakpoint counts are calculated by sample as well as by histology group.
  Bins are created using GenomicRanges::tileGenome using a one Mb window size. Genome bins above a percentage (default is 75%) of their total size being covered in uncallable regions are called as NA for all output statistics.
  The output of this notebook is three _binned_breakpoint_counts.tsv" for each dataset, and an RDS file with the histology binned data: histology_breakpoint_densities.RDS.

• 02a-plot-chr-instability-heatmaps.Rmd uses _binned_breakpoint_counts.tsv" datasets to create three heatmaps for the intersection, CNV, and SV data respectively. NA regions are gray.

• 02b-plot-chr-instability-by-histology.Rmd uses the _breaks_densities.tsv files and histology_breakpoint_binned_counts.RDS to plot breakpoint densities by short_histology group.

Summary of Custom Functions

For breakpoint analysis:

• make_granges : Given a data.frame with chr break coordinates, make a GenomicRanges object.
• break_density: Given data.frame(s) with chr break coordinates, calculate the density of the breaks.
• map_breaks_plot: Given a GenomicRanges object, use map the chromosomal coordinates to a ggplot2
• multipanel_break_plot: Given a list of GenomicRanges objects, plot them in a combined cowplot.
• breaks_cdf_plot: Given a genome wide breaks density file path, plot the CDF distribution for it by histology.