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Methodology Questions >> How to >> re: constant rate model http://www.hyphy.org/cgi-bin/hyphy_forums/YaBB.pl?num=1313508501 Message started by bioinfo_ucc on Aug 16th, 2011 at 8:28am |
Title: re: constant rate model Post by bioinfo_ucc on Aug 16th, 2011 at 8:28am
Dear Sergei,
I have just started to use Hyphy in the hope that it will help me in my project. My problem seems pretty simple or atleast to you, should be simple. I have an alignment of sequences and I have certain reasons to believe that there is some region in the middle of the alignment which has a regulatory role, hence should show enhanced conservation. And decreased synonymous (or even non-synonymous) substitution rate. I saw your MBE paper (2005- Site-to-Site Variation of Synonymous Substitution Rates) which incorporates quite complicated and parameter rich models. However I was thinking about a relatively simple approach. I could simply use the "Constant rates model". This would be my null hypothesis i.e. all sites in an alignment evolve under constant synonymous rates. Then I should have a probability of each site (codon) fitting the null model. And the outliers, that do not fit the model should be regions which, I believe, play regulatory role. Do you agree or do I have to start with a Dual model to get to this conclusion ? Regards Sankalp |
Title: Re: constant rate model Post by bioinfo_ucc on Aug 22nd, 2011 at 1:58am
Thank you very much Sergei.
Regards Sankalp |
Title: Re: constant rate model Post by bioinfo_ucc on Aug 22nd, 2011 at 4:05pm
Hi Sergei,
I think I was wrong in my presumption. In my last post, I had mentioned how I want to figure out regions within an alignment of protein coding genes with regulatory function by trying to identify sites which have a reduced dS and dN. However, reduced dS and dN simply imply that such sites are well conserved and not tolerable to any sort of substitutions. This inturn implies that the protein sequence is important, not necessarily the nucleotide sequence. If however, we find sites with low dS, irrespective of what dN is for those sites, it would imply that the selection is at the level of nucleotide and not peptide sequence. I have seen a few papers where people have tried to identify Exonic splicing enhancers by identifying regions with low dS, considering that ESE is another regulatory element in protein coding regions. Do you agree ? Regards Sankalp |
Title: Re: constant rate model Post by Sergei on Aug 25th, 2011 at 3:19pm
Hi Sankalp,
Sure, you can look for reduced dS as a proxy for nucleotide level conservation (with invariable sites being the complete extreme). You should still be able to explore this using FEL or REL on DataMonkey and plotting dS (or E[S]) over sites. Sergei |
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