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MEME interpretation - 0 branches? #1721

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glitterseaworms opened this issue Jul 11, 2024 · 4 comments
Open

MEME interpretation - 0 branches? #1721

glitterseaworms opened this issue Jul 11, 2024 · 4 comments

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@glitterseaworms
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Hello, I was wondering if we should not consider codon sites that have significant p-values but have 0 branches listed? For example:
Based on the likelihood ratio test, episodic diversifying selection has acted on 1 sites in this dataset (p≤0.05).

Codon Partition alpha non-syn rate (beta) distribution, rates : weights LRT Episodic selection detected? # branches List of most common codon substitutions at this site
168 1 0.120 0.05/2808.48 : 0.00/1.00 15.009 Yes, p = 0.0002 0 [1]GTt>AAt,GTt>TAt,GTT>TCC,GTt>TCt,TCT>AAC,tcT>tcC
@spond
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spond commented Jul 11, 2024

Dear @glitterseaworms,

This is a bit counterintuitive, but here's an explanation. For the site you provide as an example, MEME allocates 100% of the available ω weight to the positive selection regime: β = 2808.49.

When MEME calculates which, if any, branches may be subject to selection, it attempts to estimate a Bayes Factor (empirical Bayes), that β > α (or ω > 1) at that branch. However, the PRIOR probability for ω > 1 is estimated to be exactly 1, which makes the prior odds (needed to calculate Bayes Factors) infinite. So MEME cannot calculate a Bayes Factor for sites where all the weight is assigned to β > α, and you end up with the 0 estimate.

Hope this helps,
Sergei

@glitterseaworms
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Ah ok thanks for the explanation. In that case, would you say it is reasonable to hypothesize that the site may still be under diversifying selection then?

@spond
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spond commented Jul 11, 2024

Dear @glitterseaworms,

Yes, and the selection is pervasive (applies to all branches), or at least we have no ability to resolve it further down to specific branches.

Best,
Sergei

@glitterseaworms
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Thank you kindly for your help. I really appreciate you!

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