README for PyLOH 1.0

INTRODUCTION

Estimation of tumor purity is a crucial step in understanding the complex copy number landscapes of heterogeneous tumor samples through next-generation sequencing data. A prominent problem in tumor purity estimation is how to disambiguate multiple compatible solutions, as distinct combinations of tumor purity and ploidy can fit the sequencing data equivalently well. Current methods "break the tie" relying on either prior information or numerical heuristics rather than comprehensively explaining the sequencing data itself. Such approaches will lead to fundamental bias when the ground truth significantly deviates from the prior information. Here we propose a full probabilistic model-based method PyLOH that leverage the cluster pattern of loss of heterozygosity observed in paired cancer sequencing data to disambiguate multiple compatible solutions. We also introduce a novel visualization method "BAF heat map" to to characterize the cluster pattern of LOH.

INSTALL

Prerequisites

• Although not mandatory, Linux system is recommended.

• Python (2.7). Python 2.7.3 is recommended.

• Numpy(>=1.6.1). You can download the source of Numpy from here.

• Scipy(>=0.10). You can download the source of Scipy from here.

• Pysam(>=0.7). To install Pysam, you also need to install Cython first.

• matplotlib(>=1.2.0) is required to plot BAF heat map.

Altough not required by PyLOH, samtools can be useful for creating bam, bam index and fasta index files which are required by the pysam module of PyLOH.

Install from source

Download the compressed source file PyLOH-*.tar.gz and do as follows:

$ tar -xzvf PyLOH-*.tar.gz
$ cd PyLOH-*
$ python setup.py install

If you prefer to install PyLOH other than the default directory, you can also use this command:

$ python setup.py install --prefix /home/yili/

There are also config/ and bin/ folders under PyLOH-*. The config/ folder contains example priors and the bin/ folder contains useful utilities, such as the R code to run BICseq and the python script to convert BICseq results to BED file. You can copy these two folders somewhere easily accessible.