Double base substitutions annotation

[andreyurch]

Dear Inigo,

I found the following message while running the tools: "Mutations observed in contiguous sites within a sample. Please annotate or remove dinucleotide or complex substitutions for best results." I do have many double-base substitutions (due to skin cancer samples). I can annotate them, but how should I provide the file to the tool afterwards.

Best regards,
Andrey

[im3sanger]

Hi Andrey,

Thanks. Say that you have a double base substitution currently annotated as follows:

sampleID	chr	pos	ref	mut
Sample1	X	10023	C	T
Sample1	X	10024	A	T

If you input this as two mutations, dndscv will count them as two independent mutations, which is not correct if they are a double-base substitution (a single mutational event). Counting them as two independent events could lead to a likely modest inflation of the significance of the gene (if the mutations are non-synonymous) or inflation of the mutation rate overdispersion (if they are synonymous). Instead, you can input the double base substitution above as follows:

sampleID	chr	pos	ref	mut
Sample1	X	10023	CA	TT

Hope it helps,
Inigo