Code accompanying The evolutionary history of 2,658 cancers

Moritz Gerstung and Santiago Gonzalez, on behalf of the PCAWG-11 Evolution and Heterogeneity Working Group.

This repository contains analysis code for the aforementioned publication, especially, Figures 1b,e-h, 2, 4, 5 & Extended Data Figures 3, 6, 8 and 9. The output of the code is an rmarkdown html report, hosted at https://gerstung-lab.github.io/PCAWG-11.

Note that some referenced files in ref and final folders are protected access and are note part of this repository.

Contents

The code folder contains a number of scripts to run MutationTime.R to estimate the timing of point mutations and copy number gains in individual samples. This step can be parallelised across individual samples.

• code/PCAWG-functions.R A collection of utility functions. This is sourced before running. This functions also sources a number of working group output files, from ref and final folder, which are not part of the repository at the moment.
• code/VCF-annotate.R An R script to annotate point mutations and estimate the timing of copy number gains. It is usually envoked via

$ bsub < VCF-annotate.sh

which submits an array job to an LSF cluster. Input to this script are (assumed in final, not provided): * consensus copy number segments * consensus subclonal reconstruction * VCF files for SNVs and indels * inferred gender

The run time ranges from 5 minutes to about 8 hours, depending on the number of variants per sample (median about 10 minutes).

• The main code file is code/PCAWG-final.R; this is run on R-3.3.3 using

> rmarkdown::render("code/PCAWG-final.R", clean=FALSE)

The output is a html report with mixed code, results and figures, which can be found at run/PCAWG-final.html. Runtime is approximately 4hr, with most time spent on loading all data. It requires about 50Gb of memory per core.

• Experimental code can be found in PCAWG-sandbox.R.
• Code used for timing simulations is in PCAWG-simulate.R.
• modules/MutationTime.R contain the MutationTimeR submodule. Don't forget to run git submodule init.

Dependencies

The main analysis workflow is run in

R-3.3.3

Additionally it requires the following R libraries

Rsamtools
VariantAnnotation
MutationTimeR <https://github.com/gerstung-lab/MutationTimeR>
rstan
rmarkdown

Output

Main output is run/PCAWG-final.html, hosted at https://gerstung-lab.github.io/PCAWG-11/ in addition to this repository.