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Overlapping coding regions (Read 3069 times)

jlopez YaBB Newbies Offline I love YaBB 1G - SP1! Posts: 1	Overlapping coding regions Jun 2^nd, 2006 at 9:37am I am trying to apply REL for HBV sequences. Could you tell me please if I have to do some correction when I analyze overlapping coding regions? Thanks in advance. Jose Luis
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Sergei YaBB Administrator Offline Datamonkeys are forever... Posts: 1658 UCSD Gender:	Re: Overlapping coding regions Reply #1 - Jun 2^nd, 2006 at 9:42am Dear Jose, Incidentally, I am implementing an overlapping RF model for a collaborator. Stay tuned. In the meantime, the best you can do is analyze both frames separately. Cheers, Sergei
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Caro T

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Re: Overlapping coding regions
Reply #2 - Jan 4^th, 2010 at 6:31am

Dear Sergei,

Has been implemented in Hyphy a model to analyze selectives pressures in overlapping reading frames?

I was told (in the last Bioinformatic workshop) to use the Dual model for both genes... do you agree?...
Also, I read the paper where a codon substitution model for overlapping reading frames is developped... but I couldn't find it in Hyphy...

[Chung W-Y, Wadhawan S, Szklarczyk R, Pond SK, Nekrutenko A (2007) A First Look at ARFome: Dual-Coding Genes in Mammalian Genomes. PLoS Comput Biol 3(5): e91. doi:10.1371/journal.pcbi.0030091].

Thank you very much!

Caro.

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Re: Overlapping coding regions
Reply #3 - Jan 6^th, 2010 at 10:43am

Hi Caro,

As far as I know, there are no good (biologically realistic) models for estimating selection in dually coding reading frames. The suggestion you received for analyzing each reading frame separately is perfectly reasonable; but be careful to not overinterpret the results. I can send you the code for the models we fitted in the PLoS CB paper, but they tend to be very computationally intensive, and the code is not very user friendly. I will be happy to run your data through the model on our cluster and send you the results.

Sergei

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Caro T

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Re: Overlapping coding regions
Reply #4 - Jan 11^th, 2010 at 11:45am

Dear Sergei,

Thank you for your reply. Yes, I’d like you to run the codon substitution model on our data set. Do you need just an alignment?
Also, I’d like to learn how to use it on my own… but I’m a beginner with Hyphy and I’m afraid it won´t be easy…I will need some help with it.
I understand that some of the results obtained with this model are the rates "alpha", "beta10", "beta11" and "betaStop"… (Am I right?) Are these rates obtained on each codon position of the alignment or they are obtained globally for the alignment? (And in the first case, it would be possible to map where in the alignment are the SS, SN, NS and NN substitutions…?).
Besides, is there a way of using the result obtained with this model to analyze selective pressures on overlapping genes? I’m sorry if it is a naive question… and I suppose that the answer is NO according to your post (“there are no good (biologically realistic) models for estimating selection in dually coding reading frames”)… but I ask you for being completely sure…

Finally, do you think that the use of Dual model on my alignments of overlapping genes (instead of a Non synonymous model) would “break” less assumptions of the models in order to estimate selective pressures?

I figure out that in any case I should be careful with the interpretation of the results.

Thanks a lot!

Caro.

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Sergei

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Re: Overlapping coding regions
Reply #5 - Jan 14^th, 2010 at 3:20pm

Dear Caro,

The code requires an alignment (dual coding) and a phylogenetic tree. It estimates 4 global substitution rates (all relative to the baseline synonymous (in both frames) rate alpha):

R_01 - the rate of substitutions which are synonymous in the first frame and the non-synonymous in the second frame
R_10 - non-syn (frame 1)/syn (frame 2)
R_11 - non-syn (both frames)
R_stop - substitutions which introduce stop codons in one of the frames

You can interpret R_01, R_10 and R_11 as you would the traditional dN/dS ratio, but in the multiple coding alignment setting.

The code also conducts tests for

R_stop == 0. If this hypothesis is rejected (low p-value), then one of the frames in the alignment may be non-functional.
R_11 >= MIN (R_01,R_10); if this hypothesis is rejected, then the rate of accumulating dually-non-synonymous substitutions is relatively low, indicating that the overall pattern of selection is convervative.
R_10 = R_01; if this hypothesis is rejected, then one of the frames is under more/less selection than the other.

The analysis does NOT perform any site-by-site mapping, but U can fairly easily add the code that map the substitutions to classes.

The batch file is attached; download HyPhy and run it on your alignment through the analysis and let me know how it goes.

Sergei

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Caro T YaBB Newbies Offline Feed your monkey! Posts: 3	Re: Overlapping coding regions Reply #6 - Jan 18^th, 2010 at 12:56pm Dear Sergei, Thank you very much! I will let you know how it goes. Caro.
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