Question: dn/ds ratio for somatic mutation
gravatar for deepaksrna
5.3 years ago by
deepaksrna40 wrote:

HI all

I would like to calculate the dn/ds ratio for a specifc gene according to the somatic mutation data available from TCGA. Is there any tool which can help to perform.



dna mutation tcga • 2.0k views
ADD COMMENTlink modified 5.2 years ago by Juke345.0k • written 5.3 years ago by deepaksrna40
gravatar for Cyriac Kandoth
5.3 years ago by
Cyriac Kandoth5.5k
Memorial Sloan Kettering, New York, USA
Cyriac Kandoth5.5k wrote:

I'd encourage you to write your own script for this. In TCGA MAF files, column 9 determines silent or non-silent status of mutations. Silent mutations are explicitly annotated as Silent. Non-silent mutations are annotated as Missense_Mutation, Nonsense_Mutation, and Nonstop_Mutation. This website provides a good overview of the different types of mutations.

Be aware that dn/ds is used in the context of germline SNPs... to distinguish negative/positive selection pressure across generations. When doing the math on somatic SNPs, you have to be very careful how you interpret it. Tumor samples are heterogenous and not all the cells will have all the reported mutations. As you go through the literature, you will find many other reasons why cancer genetics is very different from germline genetics.

ADD COMMENTlink modified 14 months ago by _r_am32k • written 5.3 years ago by Cyriac Kandoth5.5k
gravatar for Juke34
5.2 years ago by
Juke345.0k wrote:

You can write your own script but it will be a bit more complicated than what has been described previously.

Indeed the real formula to compute the dn/ds is

[ (Number of synonymous mutation / Number of Synonymous sites) / (Number of Non-synonymous mutation / Number of Non-Synonymous sites) ]

In other therm you have to take in account the codon composition of your sequences to determine the number of Synonymous and Non-synonymous sites.

You can have a look at codeml, or MapnH.

For your information Dn/Ds is also called Ka/Ks. There is many discussion about it (e.g Best Practices/Softwares To Calculate Ka/Ks Ratio ).

ADD COMMENTlink modified 14 months ago by _r_am32k • written 5.2 years ago by Juke345.0k

Thanks for the correction. I removed the formula from my comment... and added more notes on why dn/ds makes no sense for somatic mutations... unless you're doing single cell sequencing.

ADD REPLYlink written 5.2 years ago by Cyriac Kandoth5.5k
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