Hi All,

Is there documentation for the various ways HyPhy can test for episodic selection? I understand it can do a branch-sites test a la PAML, a new an improved branchsiteREL, TestBranchDNDS.bf, and perhaps lineagedual would work. Are there others?

My specific problem is that I am testing for episodic selection in a *very* conserved protein. There are four amino acid changes along the branch that I care about; two of these aa changes have functional consequences (and are fixed in descendant lineages) and two do not  functional consequences (these two changes appear to be evolving neutrally). There also appears to be synonymous rate variation across the tree.

Ideally I would like to test for an elevated dN along this branch accounting for syn rate variation (though that may not matter for testing dN), and in the best of all possible worlds, use a branch-site like to see if the functionally important aa changes were positively selected while the non-functional aa changes fall into some other site class.

I suspect this means that the improved branchsiteREL and TestBranchDNDS.bf are the best methods (????)

Thanks
Vinny

Hi Sergei (and others),

Thanks for the info/reference. Since I am interested in selection along one (or two) specific lineages I am most interested in the identification of sites with evidence for directional selection.

I have been using the dNdSRateAnalysis.bf with dual and lineage dual because there is significant site-to-site variation in dS among codons. I am curious what your (and every else how might want to chime in) thoughts are about using the lineage dual model (when it is significantly better than dual) to ID sites under selection, and then mapping amino acid changes at those sites onto the phylogeny to ID lineages in which they were selected?

Best,
Vinny

I am definitely interested.

The lineage dual model actually seems to give meaningful results (when interpreted in a biological context), but if it hasn't been bench marked are the results likely to be unreliable?

It is interesting that the dual model does not identify any sites under selection, but that lineage dual does. My naive interpretation is that this suggests no evidence of diversifying selection, but evidence for episodic directional selection at the sites ID's from lineage dual.

Best,
Vinny

Hi Segei,

Fitting a free ratio (in PAML at least) suggests there is a lot of variation in the magnitude of the rates, but it is limited to 2-3 branches with most others having a low rate. The free rate model has essentially the same likelihood as the one rate model. This is not terribly surprising since it is a small very conserved protein; ~150aa, with only 10 aa changes in the part of the tree I care about (composed of 8 mammals with a basal divergence of ~40MYA).

What would be involved in accuracy testing? (I assume it can be done within hyphy???).

Best,
Vinny

Hi Sergei,

I've been looking through the various output files from the dNdSRateAnalysis.bf trying to get a better understanding of what the models are doing. Are the "r" values in the .fit file for Lineage Dual (for example: givenTree.Node6.r=5.242482728475014) the branch correction parameters (omega_b) in this model?

Thanks,
Vinny