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# subclonal.yaml — Complex clonal architecture with subclones
#
# Models a tumour with a four-clone hierarchy: one founding clone, two
# parallel early subclones (branching evolution), and one late subclone
# that arose within branch B.
#
# Clone tree:
#
# founding (CCF 1.0)
# ├── branch_a (CCF 0.45) — e.g. acquired KRAS mutation
# └── branch_b (CCF 0.55) — e.g. acquired TP53 mutation
# └── late_b (CCF 0.20) — e.g. acquired drug resistance allele
#
# Effective VAF for a mutation private to branch_b at 60% purity:
# VAF ≈ purity × CCF_b / 2 = 0.60 × 0.55 / 2 ≈ 0.165
#
# Suitable for benchmarking subclonal deconvolution tools (PyClone-VI,
# MOBSTER, Canopy) and clonal evolution analysis pipelines.
#
# Run:
# varforge simulate --config examples/subclonal.yaml
reference: ${reference} # set with --set reference=/path/to/hg38.fa
output:
directory: out/subclonal
fastq: true
bam: true
truth_vcf: true
manifest: true
sample:
name: SUBCLONAL_TUMOUR
read_length: 150
coverage: 60.0
platform: illumina
fragment:
model: normal
mean: 290.0
sd: 45.0
quality:
mean_quality: 36
tail_decay: 0.003
tumour:
purity: 0.60
ploidy: 2
clones:
- id: founding
ccf: 1.0
- id: branch_a
ccf: 0.45
parent: founding
- id: branch_b
ccf: 0.55
parent: founding
- id: late_b
ccf: 0.20
parent: branch_b
mutations:
random:
count: 2000
vaf_min: 0.01
vaf_max: 0.60
snv_fraction: 0.80
indel_fraction: 0.15
mnv_fraction: 0.05
# Chromosome-level copy number alterations.
copy_number:
- region: "chr8:128000000-146000000" # MYC amplification (8q24)
tumor_cn: 6
normal_cn: 2
major_cn: 5
minor_cn: 1
- region: "chr17:7500000-8000000" # TP53 locus deletion (17p13)
tumor_cn: 1
normal_cn: 2
major_cn: 1
minor_cn: 0
- region: "chr9:21900000-22100000" # CDKN2A homozygous deletion (9p21)
tumor_cn: 0
normal_cn: 2
major_cn: 0
minor_cn: 0
gc_bias:
enabled: true
model: default
severity: 1.0
seed: 3141
threads: 8