图片来源于网络MesKit

VAF - variant allele frequency

Variant allele fraction or frequency (VAF): the fraction of mutated reads for a given variant, which is a readout for the proportion of DNA mutated in the sequenced tissue.

测序时特定位点突变的reads数比上总的reads数，可以从VCF中获得。

CCF - cancer cell fraction

Cancer cell fraction (CCF): the fraction of cancer cells from the sequenced sample carrying a set of SNVs.

携带突变的癌细胞比例，可以通过pyclone（https://github.com/Roth-Lab/pyclone-vi）或sciclone（https://github.com/genome/sciclone）计算。

$$ CCF = VAF *\frac{1}{p}[pCN_t + CN_n(1-p)] $$

VAF: corresponds to the variant allele frequency at the mutated base

p: the tumor purity肿瘤纯度

CNt: the tumor locus specific copy number所在位置的拷贝数

CNn: the normal locus specific copy number (CNn was assumed to be 2 for autosomal chromosomes)正常样本的拷贝数

Clonal and subclonal mutation

根据CCF可以判断克隆或者亚克隆突变，不过不同的文章也有不同的做法。

https://www.sciencedirect.com/science/article/pii/S0002929719303878

For clonality, a mutation with a probability of >50% or the lower bound of the 95% confidence interval of its CCF >90% was classified as clonal and subclonal otherwise.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538405/

A clonal SNV will have a CCF of 1.0 (i.e., 100% of tumor cells). A subclonal mutation has a CCF less than 1.0 (for example, 0.4, or 40% of tumor cells).

https://www.nature.com/articles/s41467-019-09255-1