<?xml version="1.0"?>
<tool id="hyphy_cfel" name="HyPhy-CFEL" version="@TOOL_VERSION@+galaxy1" profile="19.09">
    <description>Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches</description>
    <macros>
        <import>macros.xml</import>
    </macros>
    <expand macro="requirements"/>
    <command detect_errors="exit_code"><![CDATA[
        @SYMLINK_FILES@
        hyphy contrast-fel
            --code '$gencodeid'
            #for $i, $branch in enumerate($branch_repeat):
                --branch-set '$branch.branch_label'
            #end for
            --srv '$srv'
            --permutations '$permutations'
            --pvalue '$pvalue'
            --qvalue '$qvalue'
            --output '$cfel_output'
            $input_file
            @INPUT_TREE@
        @ERRORS@
    ]]></command>
    <inputs>
        <expand macro="inputs"/>
        <expand macro="gencode"/>
        <repeat name="branch_repeat" title="Branch set" min="1">
            <param name="branch_label" type="text" value="Test" optional="false" label="Label for set">
                <sanitizer invalid_char="">
                    <valid initial="default" />
                </sanitizer>
            </param>
        </repeat>
        <param argument="--permutations" type="boolean" truevalue="Yes" falsevalue="No" label="Perform permutation significance tests"/>
        <param argument="--pvalue" type="float" value=".05" min="0" max="1" label="Significance value for site-tests"/>
        <param argument="--qvalue" type="float" value=".2" min="0" max="1" label="Significance value for FDR reporting"/>
        <param argument="--srv" type="select" label="Include synonymous rate variation" help = "Allow synonymous rates to vary from site to site">
            <option value="Yes">Yes (recommended)</option>
            <option value="No">No</option>
        </param>
    </inputs>
    <outputs>
        <data name="cfel_output" format="hyphy_results.json" />
    </outputs>
    <tests>
        <test>
            <param name="input_file" ftype="fasta" value="absrel-in1.fa"/>
            <param name="input_nhx" ftype="nhx" value="absrel-in1.nhx"/>
            <repeat name="branch_repeat">
                <param name="branch_label" value="Internal branches" />
            </repeat>
            <repeat name="branch_repeat">
                <param name="branch_label" value="Terminal branches" />
            </repeat>
            <output name="cfel_output" file="cfel-out1.json" compare="sim_size"/>
        </test>
    </tests>
    <help><![CDATA[
Contrast-FEL : A Test for Differences in Selective Pressures at Individual Sites among Clades and Sets of Branches
==================================================================================================================

A number of evolutionary hypotheses can be tested by comparing selective pressures among sets of branches in a phylogenetic tree. When the question of interest is to identify specific sites within genes that may be evolving differently, a common approach is to perform separate analyses on subsets of sequences and compare parameter estimates in a post hoc fashion. This approach is statistically suboptimal and not always applicable. Here, we develop a simple extension of a popular fixed effects likelihood method in the context of codon-based evolutionary phylogenetic maximum likelihood testing, Contrast-FEL. It is suitable for identifying individual alignment sites where any among the K≥2 sets of branches in a phylogenetic tree have detectably different ω ratios, indicative of different selective regimes. Using extensive simulations, we show that Contrast-FEL delivers good power, exceeding 90% for sufficiently large differences, while maintaining tight control over false positive rates, when the model is correctly specified. We conclude by applying Contrast-FEL to data from five previously published studies spanning a diverse range of organisms and focusing on different evolutionary questions.
]]>

    </help>

    <expand macro="citations">
        <citation type="doi">10.1093/molbev/msaa263</citation>
    </expand>
</tool>