Question: Effect size in power analysis when dealing with Poisson based variant caller
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gravatar for CY
5 weeks ago by
CY370
United States
CY370 wrote:

I was trying to estimate the minimum sequencing depth required to confidently detect somatic variant using Poisson distribution based variant caller (such as somatic variant caller or Pisces from illumina).

Power analysis is used which requires significance level (0.05), power / sensitivity (99%) and effect size to estimate sample size (sequencing depth). I am not sure how to calculate the effect size in such context. Can anyone share some insight? Thanks a lot.

variant calling • 115 views
ADD COMMENTlink modified 5 weeks ago by markus.riester480 • written 5 weeks ago by CY370

Yeh, but, a somatic mutation / variant at which frequency? Technically speaking, in a bulk biopsy of 1 million cells, a rare sub-population of 100 cells may harbour the key mutation that will eventually bring about metastasis. The frequency of this would be ~0.01%, though. You may want to simulate a pileup that follows a Poisson (based on its read depth) and 'randomly' impute this with variants at 'random' frequencies. Then, you could go about calculating what you need. Just typing out loud.

ADD REPLYlink modified 5 weeks ago • written 5 weeks ago by Kevin Blighe47k

I will have to give up detecting somatic variant with very low frequency (<1%) since matched normal is absence. In terms of intuitive understanding of effect size of somatic variant. I guess the VAF can be viewed as effect size(say, the frequency of noise is 1%, higher VAF of variant indicates greater effect size of such somatic variant). Does this round reasonable?

ADD REPLYlink written 5 weeks ago by CY370
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gravatar for markus.riester
5 weeks ago by
markus.riester480 wrote:

Such a power calculation is described in Carter el al. You can find a well documented implementation in our PureCN R package.

Essentially this calculates the probability of sampling sufficient supporting reads so that you can rule out a sequencing error.

ADD COMMENTlink written 5 weeks ago by markus.riester480
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