<tool id="hicexplorer_hicdetectloops" name="@BINARY@" version="@WRAPPER_VERSION@.0">
    <description>searches for enriched regions</description>
    <macros>
        <token name="@BINARY@">hicDetectLoops</token>
        <import>macros.xml</import>
    </macros>
    <expand macro="requirements" />
    <command detect_errors="exit_code"><![CDATA[
        ln -s '$matrix_h5_cooler' 'matrix.$matrix_h5_cooler.ext' &&
        @BINARY@

            --matrix  'matrix.$matrix_h5_cooler.ext'

            #if $peakWidth:
                --peakWidth $peakWidth
            #end if

            #if $windowSize:
                --windowSize $windowSize
            #end if

            #if $pValuePreselection:
                --pValuePreselection $pValuePreselection
            #end if

            #if $peakInteractionsThreshold:
                --peakInteractionsThreshold $peakInteractionsThreshold
            #end if

            #if $maximumInteractionPercentageThreshold:
                --maximumInteractionPercentageThreshold $maximumInteractionPercentageThreshold
            #end if
            #if $pValue:
                --pValue $pValue
            #end if
            #if $maxLoopDistance:
                --maxLoopDistance $maxLoopDistance
            #end if

            #if $region:
                --region '$region'
            #end if

            #if $chromosomes:
                #set $chromosome = ' '.join([ '\'%s\'' % $chrom for $chrom in str($chromosomes).split(' ') ])
                --chromosomes $chromosome
            #end if

            --statisticalTest $statisticalTest_selector

            --outFileName output_loop.bedgraph

            --threads @THREADS@ -tpc @THREADS@
]]>
    </command>
    <inputs>
        <expand macro="matrix_h5_cooler_macro" />
        <param argument="--peakWidth" type="integer" optional='true' label="Peak width" help= "The width of the peak region in bins. The square around the peak will include (2 * peakWidth)^2 bins." />
        <param argument="--windowSize" type="integer" optional='true' label="Window size" help= "The window size for the neighborhood region the peak is located in. All values from this region (exclude the values from the peak
                           region) are tested against the peak region for significant difference. The square will have the size of (2 * windowSize)^2 bins" />
        <param argument="--pValuePreselection" type="float" label="P-value preselection" help= "Only candidates with p-values less the given threshold will be considered as candidates.
                                For each genomic distance a negative binomial distribution is fitted and for each pixel a p-value given by the cumulative density function is given.
                                This does NOT influence the p-value for the neighborhood testing." value='0.05'/>
        <param argument="--peakInteractionsThreshold" type="integer" label="Minimum interaction number" help= "The minimum number of interactions a detected peaks needs to have to be considered." value='5' />
        <param argument="--maximumInteractionPercentageThreshold" type="float" value='0.1' label="Maximum interaction share" help= "For each genomic distance the maximum value is considered and all candidates need to have at least \'max_value * maximumInteractionPercentageThreshold\' interactions." />
        <param argument="--pValue" type="float" label="P-value" help= "Rejection level for the statistical test for H0. H0 is peak region and background have the same distribution." value='0.05'/>
        <param argument="--maxLoopDistance" optional='true'  type="integer" label="Maximal loop distance" help= "Maximum genomic distance of a loop, usually loops are within a distance of ~2MB." value='2000000'/>
        <param argument="--minLoopDistance" optional='true'  type="integer" label="Minimum loop distance" help= "Minimum genomic distance of a loop to be considered." value='100000'/>
        <param argument="--chromosomes" optional='true'  type="text" label="Chromosomes to include" help= "Chromosomes to include in the analysis. If not set, all chromosomes are included." />
        <param argument="--region" optional='true'  type="text" label="Chromosomes to include" help= "The format is chr:start-end." />
        <param name="statisticalTest_selector" type="select" label="Stistical test">
            <option value="wilcoxon-rank-sum" selected="True">Wilcoxon rank-sum'</option>
            <option value="anderson-darling">Anderson-Darling</option>
        </param>
    </inputs>
    <outputs>
        <data name='output_loops' from_work_dir='output_loop.bedgraph' format='bedgraph' label='Computed loops'/>
    </outputs>
    <tests>
        <test>
            <param name="matrix_h5_cooler" value="small_test_matrix.cool"/>
            <param name="maxLoopDistance" value="30000000"/>
            <param name="windowSize" value="5"/>
            <param name="peakWidth" value="2"/>
            <param name="pValue" value="0.5"/>
            <param name="pValuePreselection" value="0.55"/>
            <!-- <param name="chromosomes" value="X"/> -->
            <output name="output_loops" file="hicDetectLoops/loops.bedgraph" ftype="bedgraph" compare="sim_size"/>
        </test>
    </tests>
    <help><![CDATA[

Loop detection
==============

Computes enriched regions (peaks) or long range contacts on the given contact matrix.

hicDetectLoops can detect enriched interaction regions (peaks / loops) based on a strict candidate selection, negative binomial distributions and Anderson-Darling / Wilcoxon rank-sum tests.

The algorithm was mainly develop on GM12878 cells from Rao 2014 on 10kb and 5kb fixed bin size resolution.

_________________

Usage
-----

A command line example is available below (easily matchable in Galaxy using each field information):

̀`$ hicDetectLoops -m matrix.cool -o loops.bedgraph --maxLoopDistance 2000000 --windowSize 10 --peakWidth 6 --pValuePreselection 0.05 --pValue 0.05 --peakInteractionsThreshold 20 --maximumInteractionPercentageThreshold 0.1 --statisticTest anderson-darling`

The candidate selection is based on the restriction of the maximum genomic distance, here 2MB. This distance is given by Rao 2014. For each genomic distance a negative binomial distribution is computed and only interaction pairs with a threshold less than ``--pValuePreselection`` are accepted. Detected candidates need to have at least an interaction count of ``--maximumInteractionPercentageThreshold`` times the maximum value for their genomic distance. Please note that ``--maximumInteractionPercentageThreshold`` was introduced with HiCExplorer release 3.2. Earlier versions did not have this parameter yet and therefore their outputs may differ. In a second step, each candidate is considered compared to its neighborhood. This neighborhood is defined by the ``--windowSize`` parameter in the x and y dimension. Per neighborhood only one candidate is considered, therefore only the candidate with the highest peak values is accepted. As a last step, the neighborhood is split into a peak and background region (parameter ``--peakWidth``). The peakWidth can never be larger than the windowSize. However, we recommend for 10kb matrices a windowSize of 10 and a peakWidth of 6.

The output file (´´-o loops.bedgraph``) contains the x and y position of each loop and its corresponding p-value of the Anderson-Darling test.

`1   120000000       122500000       1       145000000       147500000       0.001`

The results can visualized via hicPlotMatrix:

`$ hicPlotMatrix -m matrix.cool -o plot.png --log1p --region 1:18000000-22000000 --loops loops.bedgraph`

.. image:: $PATH_TO_IMAGES/hicDetectLoops.png
   :width: 50%


For more information about HiCExplorer please consider our documentation on readthedocs.io_.

.. _readthedocs.io: http://hicexplorer.readthedocs.io/en/latest/index.html

]]></help>
    <expand macro="citations" />
</tool>