Next-generation sequencing (NGS) and the third generation sequencing (TGS) have recently allowed us to develop algorithms to quantitatively dissect the extent of het- erogeneity within a tumour, resolve cancer evolution history and identify the somatic variations and aneuploidy events. Simulation of tumor NGS and TGS data serves as a powerful and cost-effective approach for benchmarking these algorithms, however, there is no available tool that could simulate all the distinct subclonal genomes with diverse aneuploidy events and somatic variations according to the given tumor evolution history. We provide a simulation package, Pysubsim-tree, which could simulate the tumor genomes according to their evolution history defined by the somatic variations and aneuploidy events.
Pysubsim-tree could be run individually or strung with art_illumina, bwa and samtools to generate Next-Generation Sequencing (NGS) reads according to the different cancer genomes, which can be mixed with specified proportions.
python $PYSUBSIMTREEPATH/pysubsimtree.py -c $CONFIG_PATH/ini.config -p $PREFIX
A full demo is given in ./test.
In Pysubsim-tree, Node labelled 1 is normal genome.
Node labelled 1.1 is tumor subclone genome, Node 1 is parent node of Node 1.1.
./test/config/init.conf main configuration file
[pysubsimtree_settings]
# Tumor evolution tree configuration file
SV_config_file=/media/d/github/pysubsimtree/test/config/variantTree.conf
# reference genome
ref_fasta=/media/d/github/pysubsimtree/test/small.fa
# dbsnp file
dbsnp=/media/d/github/pysubsimtree/test/small.vcf
# number of germline snps
germline_num=2
# ratio of heterozygou germline snps
hyp_rate=0.5
# chromosome
chrome=chr1
# Tumor subpopulation fraction configuration file
population_fraction_config_file=/media/d/github/pysubsimtree/test/config/pf_config
./test/config/variantTree.conf Tumor evolution tree configuration file
# This is variant tree configuration file
# The sv configuration
#
# CNV
# Variant node label Variant node type Variant type chrom Length of CNVs Copy number Genotype Number
1.1 SV CNV chr1 2 0 NONE 1
1.3.1 SV CNV chr1 2 0 NONE 1
1.3.1 SV CNV chr1 2 1 P 1
#1.1 SV CNV chr1 2 1 M 1
1.3.1 SV CNV chr1 2 2 PP 1
1.2 SV CNV chr1 2 2 MM 1
1.2.1 SV CNV chr1 2 3 PPM 1
#1.2.1 SV CNV chr1 2 3 PMM 1
#1.2.1 SV CNV chr1 2 3 MMM 1
#1.2.1 SV CNV chr1 2 4 PPPP 1
#1.2.1 SV CNV chr1 2 4 PPPM 1
#1.3 SV CNV chr1 2 4 PPMM 1
#1.3 SV CNV chr1 2 4 PMMM 1
1.3.1 SV CNV chr1 2 4 MMMM 1
#
# INVERTION
# Variant node label Variant node type Variant type chrom haplotype(Paternal or Maternal) index of chromatid Length Genotype Number
1.3.1 SV INVERTION chr1 P 0 4 2
#
# TANDEMDUP
# Variant node label Variant node type Variant type chrom haplotype(Paternal or Maternal) index of chromatid Length Number
1.3.1 SV TANDEMDUP chr1 P 0 4 2 2
#
# INSERTION
# Variant node label Variant node type Variant type chrom haplotype(Paternal or Maternal) index of chromatid Length Genotype Number
1.3.1 SV INSERTION chr1 P 0 4 2
#
# DELETION
# Variant node label Variant node type Variant type chrom haplotype(Paternal or Maternal) index of chromatid Length Genotype Number
1.3.1 SV DELETION chr1 M 0 4 2
#
# TRANSLOCATION
# Variant node label Variant node type Variant type chrom from haplotype(Paternal or Maternal) from index of chromatid from Length chrom to haplotype(Paternal or Maternal) to index of chromatid to Number
1.3.1 SV TRANSLOCATION chr1 M 0 4 chr1 P 0 2
#
# SNV
# Variant node label Variant node type chrom is heterozygous is overlaped number
1.3.1 SNV chr1 FALSE TRUE 2 2
1.3.1 SNV chr1 TRUE TRUE 2 2
1.3.1 SNV chr1 FALSE FALSE 2 2
#
# Aneuploidy event
# Variant node label Variant node type chrom ploidy number before ploidy number after ploidy status before ploidy status after
1.3 PLOIDY chr1 2 1 PM PPM
./test/config/pf_config Tumor subpopulation fraction configuration file
#name fraction
1 0.2
1.1 0.3
1.2 0.2
1.2.1 0.1
1.3 0.1
1.3.1 0.1