This is the repository for the analysis scripts accompanying the manuscript for The history of chromosomal instability in genome doubled tumors. The repository for GRITIC, the tool developed in this work can be found here.

These scripts are used run GRITIC on the PCAWG and Hartwig cohorts. They are also used to build simulated samples used to evaluate GRITIC, using PCAWG and Hartwig samples as the initial framework. Access to the original PCAWG and Hartwig data is required to run these scripts.

• HartwigDataLoader.py - A data loader for the Hartwig cohort.
• hartwig_handler.py Runs GRITIC on the Hartwig cohort.
• PCAWGDataLoader.py - A data loader for the PCAWG cohort..
• pcawg_handler.py Runs GRITIC on the PCAWG cohort.
• SampleSimulator.py Produces simulated tumor samples from a template.
• state_validation_run.py Simulates samples and runs through GRITIC.
• state_validation_run_titrate.py Simulates samples and runs through GRITIC.

These scripts produce the figures for the manuscript.

• arm_pre_post.py - A precursor script to generate a table for figures 4A,B and supplementary figures 37-41. Requires pre_post_non_gain.py and pre_post_non_loss.py to be run first.
• cancer_type_parsimony.py Produces figure 2D and supplementary figures 15D,E.
• cn_wgd_figures.py Produces figures 1A-C and supplementary figure 1. Requires access to PCAWG and Hartwig copy number and for hartwig_pcawg_copy_number_export.R to be run first.
• combinesamplegainplots.py Produces supplementary figures 19 and 26.
• DataTools.py Helper functions for data loading.
• evaluate_parsimony_penalty.py Evalutes the effect of the non-parsimony penalty on parsimony inference, a precursor to supplementary figures 17 and 18.
• event_proportions_relative_to_wgd_probabilistic.py Produces figures 4C,D and supplementary figures 42-49.
• fraction_of_gains_job.py Produces figure 3D and supplementary figures 28A-B. Requires pre_post_permute_job.py to be run first.
• gain_distributions_across_samples.py Produces figure 3C.
• GainClassificationAnalysis.R Produces supplementary figure 36, requires access to PCAWG structural variant data.
• GainClassifier.R Helper script for GainClassificationAnalysis.R.
• generic_gain_histograms.py Produces supplementary figure 27.
• hartwig_multiregion.py Produces supplementary figure 12. Requires raw data to run.
• hartwig_pcawg_copy_number_export.R A precursor script for cn_wgd_figures.py. Requires access to PCAWG and Hartwig copy number.
• major_3_4_analysis.py Produces supplementary figure 20.
• major_cn_timing_job.py Produces figures 2E,F and supplementary figure 22.
• make_sample_timing_plots.py Plots sample gain timing posteriors, a precursor to supplementary figures 19 and 26.
• min_dist_nearest_timing.R Helper function for permutation_final_prior_true.R and Run_WDnearest_prior_true.R.
• pan_gain_probabilistic.py Produces figure 3B and supplementary figures 24 and 25.
• parsimony_plots_with_bootstrapping.py Produces figure 3D and supplementary figures 15A,B and 16.
• permutation_final_prior_true.R Precursor script for Sync_Gain_04092024.R.
• plot_parsimony_prior_evaluations.py Produces supplementary figures 17 and 18.
• plot_wgd_sampling.py A helper script to produce figure 3B and supplementary figures 24 and 25.
• plot_wgd_timing_event_proportions.py Produces figures 3F,G and supplementary figures 30-33.
• plot_passage_cn_changes.R Produces figure 2B. Requires process_cn_passage_data.py to be run first.
• PlotTiming_posteriors.R Helper script for Sync_Gain_04092024.R.
• PlotTiming.R Helper script for Sync_Gain_04092024.R.
• pre_post_correlations_corrected.R Produces figures 4A,B and supplementary figures 37-41. Requires arm_pre_post.py to be run first.
• pre_post_major_cn.py Produces supplementary figures 21.
• pre_post_non_gain.py Precursor script to produce aggregated gain timing files. Required for arm_pre_post.py and event_proportions_relative_to_wgd_probabilistic.py.
• pre_post_non_loss.py Precursor script to produce aggregated loss timing files. Required for arm_pre_post.py and event_proportions_relative_to_wgd_probabilistic.py.
• pre_post_permute_job.py Precursor script to produce aggregated loss timing files.
• process_cn_passage_data.py Precursor script to produce figure 2B. Requires access to tetraploid passage CN data.
• route_calibration_plot.py Produces supplementary figures 8-11.
• route_difference_analysis.pyProduces supplementary figures 13-14.
• Run_WDnearest_prior_true.R Precursor script for Sync_Gain_04092024.R.
• Sync_Gain_04092024.R Produces figures 3H,I and supplementary figures 34D-F.
• timing_matchup_sim.py Produces figures 1H and supplementary figures 3-7.
• usarc_analysis_medicc.ipynb Produces figure 3A.
• wgd_calling_analysis_script.py Produces supplementary figure 51.
• wgd_constraint_analysis.py Produces supplementary figure 2.
• wgd_dist_permutation_job.py Produces figure 3E and supplementary figures 28C,D and 29.
• WGD_Chromothripsis_Fisher_Exact.R Produces supplementary figure 35, requires access to PCAWG chromothripsis data.