Hi, I'm working on a virus dataset that is characterized by many historical host shifts among many different host species, which now each maintain mostly independent epidemiological cycles that are subject to purifying selection. I have datasets for 3 genes and I am interested in identifying sites under positive selection which might be signals of host adaptation. There are multiple virus sequences for each host-specific virus lineage for each gene.

If I analyze these datasets under FEL (or REL or SLAC), it seems like I would overestimate dS by including multiple representatives per viral lineage (since any selection would have already happened on the branches leading to that clade). It seems like MEME would be a good solution here since selection would be expected to be episodic over time. My first question is whether that sounds like a reasonable approach or would it be better to reduce the dataset to have only 1 representative sequence per clade per gene to reduce the purifying selection happening within host-associated clades and use site-only methods?

Second, I have tried both FEL and MEME on the full dataset, and the latter identifies more sites under selection than FEL, which makes sense to me. However, there are a few sites that are identified as being under positive selection (p<0.1) by FEL, but not by MEME. Is there an explanation for how a site could be under selection when averaging across all branches, but not episodically when only a subset of branches are considered? If there a way to come to some consensus on this, I would appreciate any advice.

Thanks,
Daniel

Hi Sergie,

Thanks for your quick reply. I am not being allowed to post links, but the upload number for both the FEL and MEME jobs is: 21233339386635.1

However, I had a closer look at the results for each run for this dataset and another that had apparently conflicting results and in each case the FEL result was just barely significant (p<0.099) and the MEME result was just barely non-significant (p=0.10; codon 357). So maybe not so different after all?

More generally, this brings up the issue of p values for these analyses. Are there guidelines based on sample size for what is appropriate?

Thanks,
Daniel

Great. Thanks for clearing that up.

Daniel

Hi Daniel,

Sure; please send me an e-mail and I can send you what we currently have submitted. What you see if perfectly normal though -- bursts of positive selection are often followed by extensive conservation -- on average over all branches (FEL), this will yield dN/dS < 1, while with MEME, a small proportion of branches will be correctly assigned to a class with dN>dS.

Sergei

streicker wrote on Jan 6^th, 2012 at 10:52am: