Hi Sergei,
   We are finding the best nucleotide substitution model for a number of alignments using the best nucleotide substitution analysis (with gamma+inv rates) in HYPHY.  From this analysis, we get an estimate of alpha for each alignment.  However, the alpha estimate obtained using the best nucleotide substitution model does not always agree with the alpha obtained using the HYPHY GUI, where we input the chosen nucleotide model and use the built in likelihood method to estimate the rate parameters (including alpha).  Can you help? I have listed the steps involved for each method and can email a problem alignment if you'd like.
   
1 - Standard Analysis: NucModelCompare:-Global w/variation - Once - Gamma+Inv- 4 rate classes - significance of .0002;

2 - Hyphy GUI: created a new model (011010) from the NucModelCompare results with het. rates; applied this model to the whole alignment (build likelihood, optimize) and got an estimate of alpha.

The problem is that the two estimates of alpha do not agree. For one alignment, method 1 yielded an alpha of 2.15, while method 2 yieleded an alpha of 1.41.

Thanks very much,
Jennifer Knies

Dear Jennifer,

I am pretty sure that the GUI based model does not include the invariant rate class - hence the difference in the results. It's not something included in the GUI tools, although you can add it relatively easily. Download Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to Login into the SubsitutionClasses/RateHeterogenity folder of your HyPhy distribution and restart HyPhy.

When you create a GUI model (using the model editor in GUI), make sure you set WHICH rate variation model you want to use from the Model->Rate Variation menu.

Cheers,
Sergei