Variant allele frequency or allelic balance?

[Kulvait]

Hi,
we are conducting some study of cancer genomes or their parts. We are studying clonality in single samples. We do a NGS and when we obtain a mutation, we typically observe it in 1%-100% of reads.

We are explaining our observation by the fact that cell populations in our samples are different and therefore we can have mutation present in say 10% of cells.

However the question is how to call that 10%. When performing analysis, this number is reported as Allelic Balance. But colleagues of mine tend to report it as Variant allele frequency. I feel that VAF is a term that is used frequently with regard to populations of many individuals and therefore I am unsure how to call the proportion of the cells (or alleles) in the sample that carry particular variant.

Thank you, Vojtech.

[Brian Bushnell]

I think variant allele frequency is the correct term. Variant callers typically use "AF" or "Allele Frequency", and it does not imply a population study, just the fraction of reads indicating the variant allele, regardless of whether they came from an individual or a population.

[Kulvait]

I am not aware of any single variant caller that assigns to AF this ratio. I know that samtools do assign that as allele balance (AB).

Instead if you search for Allele frequency you get as a first result

Allele frequency, or gene frequency, is the relative frequency of an allele (variant of a gene) at a particular locus in a population, expressed as a fraction or percentage. Specifically, it is the fraction of all chromosomes in the population that carry that allele.

Can you please send me an example of variant caller that really assigns AF to this ratio?

[raimotanzi]

you should try DEPArray sorting to isolate 100% pure tumor cells from even your lowest cellularity sample, fresh or FFPE. At that point your VAF will only display as 0%-50% -100% on the pure cells. You will easily detect LoH, CNV, somatic variants.
You could also try to sequence single cells, afte WGA.

[jilguero888]

I am not aware of any single variant caller that assigns to AF this ratio. I know that samtools do assign that as allele balance (AB).

Instead if you search for Allele frequency you get as a first result

Allele frequency, or gene frequency, is the relative frequency of an allele (variant of a gene) at a particular locus in a population, expressed as a fraction or percentage. Specifically, it is the fraction of all chromosomes in the population that carry that allele.

Can you please send me an example of variant caller that really assigns AF to this ratio?

yes, you are right