CisChecker

Introduction

CisChecker is a software to check if two mutations in a same gene are located in the same allele (in cis) or not (in trans) using next-generation sequencing data.

Citation

Please cite the following paper when using CisChecker.

Saito, Y., Koya, J., Araki, M. et al. Landscape and function of multiple mutations within individual oncogenes. Nature 582, 95–99 (2020). https://doi.org/10.1038/s41586-020-2175-2

Dependency

Python

Python (2.7), pysam (0.14.1), pandas(0.16.2) packages (Other versions are not checked)

Input files

Mutation files

Mutations are provided in a Mutation Annotation Format (MAF) file.

Sample sheet of BAM files

Sample list needs be tab-delimited.

Each line contains a sample name, a tab character, and a path to the BAM file of the sample.

sample1	/home/usr/bam/sample1.bam
sample2	/home/usr/bam/sample2.bam

How to use

Before usage, type the sentence below.

python setup.py install --user

$ cischecker -h
usage: cischecker [-h] [--version] {listing,cis_check} ...

positional arguments:
  {listing,cis_check}
    listing            Make multiple mutation list from A Mutation Annotation
                       Format (MAF) file (.maf)
    cis_check          merge, compress and index break point file generated by
                       parse function

optional arguments:
  -h, --help           show this help message and exit
  --version            show program's version number and exit

CisChecker consists of two steps.

1, make multiple mutation lists

First, make multiple mutation file from MAF file.

Multiple mutation file returns lists with multiple mutations in a same gene in a same sample.

If there are more than three mutations in a same gene in a same sample, list of all two combinations will be returned.

$ cischecker listing -h
usage: cischecker listing [-h] [-g GENE] [-s SAMPLE] [-v] input.maf output_file

positional arguments:
  input.maf             path to input MAF file
  output_file           path to output file

optional arguments:
  -h, --help            show this help message and exit
  -g GENE, --gene GENE  specify the gene you want to check (if you want to choose multiple genes, separate them with colon) (default: all genes)
  -s SAMPLE, --sample SAMPLE
                        specify the sample you want to check (if you want to choose multiple samples, separate them with colon) (default: all samples)
  -v, --vaf             use VAF (variant allele fraction) information

Example

$ cischecker listing example/test_maf.txt example/test_list.txt

2, check if multiple mutations are in cis or not

Second, check if multiple mutations are located in cis.

$ cischecker cis_check -h
usage: cischecker cis_check [-h] [--baseq BASEQ] [--mapq MAPQ] [--overlaps] [--stepper {all,nofilter,samtools}] [--orphans] [-v] [-m] [-d] multiple_mutation_list sample_list.txt output_file

positional arguments:
  multiple_mutation_list
                        path to multiple mutation file (generated by listing function)
  sample_list.txt       path to sample list
  output_file           path to output file

optional arguments:
  -h, --help            show this help message and exit
  --baseq BASEQ         Minimum base quality (samtools option; default = 0) (default: 0)
  --mapq MAPQ           Minimum mapping quality (samtools option; default = 0) (default: 0)
  --overlaps            If set to True, detect if read pairs overlap and only take the higher quality base (samtools option; default True) (default: True)
  --stepper {all,nofilter,samtools}
                        The stepper controls how the iterator advances. (samtools option; default all) (default: all)
  --orphans             Ignore orphans (paired reads that are not in a proper pair) (samtools option; default True) (default: True)
  -v, --vaf             use VAF (variant allele fraction) information (default: False)
  -m, --mapping_difference
                        Indel mapping differs between mapping tools. If MAF file and BAM file were mapped with a different mapping tool (or same tool with different parameters), use this argument. (default: False)
  -d, --debug           debug function (default: False)

Example

$ cischecker cis_check example/test_list.txt example/sample_list.txt example/test_output.txt