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Multiple methods and the FUBAR paper (Read 7686 times)
Day
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Multiple methods and the FUBAR paper
Mar 26th, 2013 at 6:48am
 
Hi there,

I'm trying to ascertain which would be the best method(s) for trying to find positively selected sites from a small number of MHC Class I exon 3 sequences (2 species together, n=26 (10 of species 1 and 16 of species 2).

I am currently just running REL, MEME and FUBAR and hoping to get some congruence between them. I've read that REL is good for small sample sizes and the site seems to strongly recommend using MEME and FUBAR anyway as they are quite encompassing techniques. However, you might have guessed I'm incredibly new to this - any suggestions would be very helpful indeed!

I was hoping to be able to read up about the FUBAR method but my university does not provide access to Molecular Biology and Evolution journal, so not sure if it would be relevant in my situation?

Many thanks,

Day
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konrad
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Re: Multiple methods and the FUBAR paper
Reply #1 - Mar 26th, 2013 at 2:33pm
 
Dear Day,

REL is an older method, and has been superseded by MEME and FUBAR for most purposes - what you read about small sample sizes will have been written before MEME and FUBAR came out. We recommend MEME if you want to take heterotachy (rates changing over time) into account, e.g. for detecting sites which experienced positive selection _some of the time_ (rather than on average over all time, as assumed by most methods). FUBAR does not take heterotachy into account, but instead provides robustness against heterogeneity of selective strength; however, its main advantage is the massive speed increase. (The FUBAR paper compares it with FEL and REL (we think it is better than both), but not MEME - so you probably don't need to read the paper for your purposes.)

I should also point out that none of these methods (or other phylogenetic methods) are designed for intra-population data, which reflects polymorphism rather than divergence - in your case this may complicate interpretation of results as you have multiple samples from the same species. E.g. see Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login Login
for a discussion of why phylogenetic methods may not be appropriate for such data.

Hope this helps,
Konrad
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Day
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Re: Multiple methods and the FUBAR paper
Reply #2 - Mar 27th, 2013 at 11:11am
 
Hi Konrad,

Thank you very much for your helpful response. I am concerned I might have misunderstood how I am able to identify positively selected sites; I have read a few papers that used datamonkey's REL & FEL methods etc to infer PSS by analysing sequences aligned from across species 4 or so species. I thought by including two different but related species I would avoid the problems highlighted in Kryazhimskiy & Plotkin's paper?

I guess the sensible solution to finding PSS in my species would thus be to use both MEME and FUBAR (and look for congruence) and look across a broader group of species (there's 8 or so species now with available genetic info)?

Many thanks again. I'm slowly trying to unravel the mysteries of it all.

Kind regards,

Day

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