HyPhy-FEL (version 2.5.47+galaxy0)

Input FASTA or NEXUS file:

If the input file type is NEXUS and it includes a valid newick tree, that tree will override an uploaded newick tree

Input newick file:

Genetic code:

Set of branches to test:

P-value:

Include synonymous rate variation:

Allow synonymous rates to vary from site to site

Compute profile likelihood confidence intervals for each variable site:

Perform parametric bootstrap resampling to derive site-level null LRT distributions:

Warning: This will result in a significantly slower analysis. This parameter specifies the maximum number of replicates per site.

Optimization precision for preliminary fits:

FEL : Fixed effects likelihood

What question does this method answer?

Which site(s) in a gene are subject to pervasive, i.e. consistently across the entire phylogeny, diversifying selection?

Recommended Applications

The phenomenon of pervasive selection is generally most prevalent in pathogen evolution and any biological system influenced by evolutionary arms race dynamics (or balancing selection), including adaptive immune escape by viruses. As such, FEL is ideally suited to identify sites under positive selection which represent candidate sites subject to strong selective pressures across the entire phylogeny.

FEL is our recommended method for analyzing small-to-medium size datasets when one wishes only to study pervasive selection at individual sites.

Brief description

FEL (Fixed Effects Likelihood) estimates site-wise synonymous (alpha) and non-synonymous rates (beta), and uses a likelihood ratio test to determine if beta != alpha at a site. The estimates aggregate information over all branches, so the signal is derived from pervasive diversification or conservation. A subset of branches can be selected for testing as well, in which case an additional (nuisance) parameter will be inferred -- the non-synonymous rate on branches NOT selected for testing.

Input

A FASTA sequence alignment.
A phylogenetic tree in the Newick format

Note: the names of sequences in the alignment must match the names of the sequences in the tree.

Output

A JSON file with analysis results (http://hyphy.org/resources/json-fields.pdf). A custom visualization module for viewing these results is available (see http://vision.hyphy.org/FEL for an example)

Tool options

--code              Which genetic code to use

--branches          Which branches should be tested for selection?
                        All [default] : test all branches

                        Internal : test only internal branches (suitable for
                        intra-host pathogen evolution for example, where terminal branches
                        may contain polymorphism data)

                        Leaves: test only terminal (leaf) branches

                        Unlabeled: if the Newick string is labeled using the {} notation,
                        test only branches without explicit labels
                        (see http://hyphy.org/tutorials/phylotree/)

 --pvalue           The significance level used to determine significance

 --srv              Include site-to-site synonymous rate variation?
                        Yes [default] or No