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Question on YangNielsonBranchSite2005.bf (Read 1957 times)
Djm59
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Question on YangNielsonBranchSite2005.bf
Dec 28th, 2009 at 3:14am
 
Hi there,

I hope you don't mind spending a bit time to answer my question!

A reviewer has asked me to perform (with PAML) a branch-site test (i.e. improved Yand and Nielson model) to examine directional selection on a branch where I observed a notable increase in dN/dS relative to prior lineages.

I have been avoiding using PAML until now, since I havent found a test I couldnt perform equally well in HyPhy. My main question here is: how does your "YangNielsonBranchSite2005.bf" differ in relation to the PAML test? Further, what are the relative merits of this test vs. say a 2-rate FEL specifiying the branch of interest?

I have had a small play with the YangNielsonBranchSite2005.bf, specifying the branch of interest as foreground and indeed find many sites assigned to class 2A. However, I can't find any details of the PAML-type LRT between the alternative and null models to actually infer positive selection initially?

Any insights would be most appreciated!

Best Regards

Dan
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Sergei
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Re: Question on YangNielsonBranchSite2005.bf
Reply #1 - Dec 28th, 2009 at 6:29am
 
Dear Dan,

The branch-site test (when it works) can only test for DIVERSIFYING (i.e. elevated dN/dS) selection on a branch, not DIRECTIONAL selection. FEL can, likewise test only for diversifying selection. In some cases directional selection can be detected by both tests. YangNielsonBranchSite2005.bf should be equivalent to the PAML implementation (except HyPhy doesn't implement BEB). I have found branch site tests to be subject to serious issues due to model misspecification, i.e. they can tell you that selection happens on branch A, when in fact it is happening elsewhere in the tree, but I don't think there is a published reference for that. I am attaching an unpublished simulation study we did a few years ago - it has some background on the test as well.

The relative merit of REL-type tests (BranchSite) is that they are geared to tell you whether there was elevated dN/dS along branch A somewhere in the alignment (under strong model assumptions), but not so much to detect which SITES experienced said selection for small alignments.

Sergei
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