<tool id="hicexplorer_hicpca" name="@BINARY@" version="@TOOL_VERSION@+galaxy@VERSION_SUFFIX@">
    <description>compute the principal components for A / B compartment analysis</description>
    <macros>
        <token name="@BINARY@">hicPCA</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' &&
        mkdir output &&
        @BINARY@ --matrix 'matrix.$matrix_h5_cooler.ext'

        @CHROMOSOME_LIST@

        #set $eigenvectors = ' '.join([ '\'%s\'' % $eigenvector for $eigenvector in str($whichEigenvectors).split(' ') ])
       --whichEigenvectors $eigenvectors
       
        #set $eigenvectors_output = ' '.join([ '\'output/pca%s.%s\'' % ($eigenvector, $outputFormat) for $eigenvector in str($whichEigenvectors).split(' ') ])

        --outputFileName $eigenvectors_output
        --format $outputFormat

        #if $ligation_factor:
            $ligation_factor
        #end if

        #if $ignoreMaskedBins:
            $ignoreMaskedBins
        #end if

        #if $extra_track_conditional.extra_track_selection == 'gene_density':
            --extraTrack '$extra_track_conditional.extraTrack'
        #elif $extra_track_conditional.extra_track_selection == 'histon_mark':
            --extraTrack '$extra_track_conditional.extraTrack'
            --histonMarkType '$extra_track_conditional.histonMarkType'
        #end if

        #if $pearsonMatrix:
            --pearsonMatrix pearson.$matrix_h5_cooler.ext
        #end if

        #if $obsexpMatrix:
            --obsexpMatrix obsexp.$matrix_h5_cooler.ext
        #end if

        #if $pearsonMatrix:
            && mv pearson.$matrix_h5_cooler.ext pearson
        #end if

        #if $obsexpMatrix:
            && mv obsexp.$matrix_h5_cooler.ext obsexp
        #end if

]]>
    </command>
    <inputs>
        <expand macro="matrix_h5_cooler_macro" />
        <param name="outputFormat" type="select" label="Output file format">
            <option value="bigwig" selected="true">bigwig</option>
            <option value="bedgraph">bedgraph</option>
        </param>

        <expand macro="chromosome_list" />
        <param argument="--whichEigenvectors" optional="true" type="text" value="1 2" label="Eigenvectors to compute" help= "Define the eigenvectors that should be computed as a list. For example 1 2 5 to compute the first, second and fifth eigenvetor." />

        <param name="ligation_factor" type="boolean" truevalue="--ligation_factor" label="Multiplies a scaling factor to each entry of the expected matrix to take care of the proximity ligation" />
        <param name="ignoreMaskedBins" type="boolean" truevalue="--ignoreMaskedBins" label="This option removes the masked bins before the PCA is computed" />

        <conditional name="extra_track_conditional">
            <param name="extra_track_selection" label="Extra track type" type="select">
                <option value="" selected="true">No track</option>
                <option value="gene_density">Gene density</option>
                <option value="histon_mark">Histon mark coverage</option>
            </param>
            <when value="gene_density" >
                <param name="extraTrack" type="data" format="bed" label="Correlate PCA with e.g. gene density or histon marks to flip sign" />
            </when>
            <when value="histon_mark">
                <param name="extraTrack" type="data" format="bed,bigwig" label="Correlate PCA with e.g. gene density or histon marks to flip sign" />
                <param name="histonMarkType" type="select" label="Histon mark type">
                    <option value="active" selected="true">active</option>
                    <option value="inactive">inactive</option>
                </param>
            </when>
            <when value="" />
        </conditional>
        <param argument="--pearsonMatrix" type="boolean" truevalue="--pearsonMatrix" falsevalue="" label="Return internally used Pearson matrix" />
        <param argument="--obsexpMatrix" type="boolean" truevalue="--obsexpMatrix" falsevalue="" label="Return internally used observed / expected matrix" />

    </inputs>
    <outputs>
        <data format="bedgraph" name="pca">
            <discover_datasets pattern="__name_and_ext__" directory="output" visible="true" />
            <change_format>
                <when input="outputFormat" value="bigwig" format="bigwig" />
            </change_format>
        </data>

        <data name="pearson_outfile" from_work_dir="pearson" format="cool" label="${tool.name} on ${on_string}: Pearson matrix">
            <filter>pearsonMatrix</filter>
            <change_format>
                <when input_dataset="matrix_h5_cooler" attribute="ext" value="h5" format="h5"/>
            </change_format>
        </data>
        <data name="obsexp_outfile" from_work_dir="obsexp" format="cool" label="${tool.name} on ${on_string}: observed / expected matrix">
            <filter>obsexpMatrix</filter>
            <change_format>
                <when input_dataset="matrix_h5_cooler" attribute="ext" value="h5" format="h5" />
            </change_format>
        </data>
    </outputs>
    <tests>
        <test expect_num_outputs="1">
            <param name="matrix_h5_cooler" value="small_test_matrix.cool" />
            <param name="outputFormat" value="bigwig" />
            <conditional name="extra_track_conditional">
                <param name="extra_track_selection" value="" />
            </conditional>
             <output name="pca">
                <discovered_dataset designation="pca1" file="hicPCA/pca1_test1.bw" ftype="bigwig" compare="sim_size" delta="100000" />
                <discovered_dataset designation="pca2" file="hicPCA/pca2_test1.bw" ftype="bigwig" compare="sim_size" delta="100000" />
            </output>

        </test>
        <test expect_num_outputs="1">
            <param name="matrix_h5_cooler" value="small_test_matrix.cool" />
            <param name="outputFormat" value="bigwig" />
            <param name="ligation_factor" value="True" />

            <conditional name="extra_track_conditional">
                <param name="extra_track_selection" value="" />
            </conditional>
            <output name="pca">
                <discovered_dataset designation="pca1" file="hicPCA/pca1_test1.bw" ftype="bigwig" compare="sim_size" delta="100000" />
                <discovered_dataset designation="pca2" file="hicPCA/pca2_test1.bw" ftype="bigwig" compare="sim_size" delta="100000" />
            </output>

        </test>
        <test expect_num_outputs="1">
            <param name="matrix_h5_cooler" value="small_test_matrix.cool" />
            <param name="outputFormat" value="bigwig" />
            <param name="ignoreMaskedBins" value="True" />

            <conditional name="extra_track_conditional">
                <param name="extra_track_selection" value="" />
            </conditional>

            <output name="pca">
                <discovered_dataset designation="pca1" file="hicPCA/pca1_test1.bw" ftype="bigwig" compare="sim_size" delta="100000" />
                <discovered_dataset designation="pca2" file="hicPCA/pca2_test1.bw" ftype="bigwig" compare="sim_size" delta="100000" />
            </output>
        </test>
        <test expect_num_outputs="1">
            <param name="matrix_h5_cooler" value="small_test_matrix.h5" />
            <param name="outputFormat" value="bigwig" />
            <conditional name="extra_track_conditional">
                <param name="extra_track_selection" value="gene_density" />
                <param name="extraTrack" value="dm3_genes.bed.gz" />
            </conditional>

            <repeat name="chromosome_list">
                <param name="chromosomes" value="chrX" />
            </repeat>
            <repeat name="chromosome_list">
                <param name="chromosomes" value="chrXHet" />
            </repeat>

            <output name="pca">
                <discovered_dataset designation="pca1" file="hicPCA/pca1_test2.bw" ftype="bigwig" compare="sim_size" delta="100000" />
                <discovered_dataset designation="pca2" file="hicPCA/pca2_test2.bw" ftype="bigwig" compare="sim_size" delta="100000" />
            </output>
        </test>
        <test expect_num_outputs="3">
            <param name="matrix_h5_cooler" value="small_test_matrix.h5" />

            <param name="outputFormat" value="bigwig" />
            <conditional name="extra_track_conditional">
                <param name="extra_track_selection" value="" />
            </conditional>
            <param name="pearsonMatrix" value="True" />
            <param name="obsexpMatrix" value="True" />

            <repeat name="chromosome_list">
                <param name="chromosomes" value="chrX" />
            </repeat>
            <repeat name="chromosome_list">
                <param name="chromosomes" value="chrXHet" />
            </repeat>

            <output name="pca">
                <discovered_dataset designation="pca1" file="hicPCA/pca1_test3.bw" ftype="bigwig" compare="sim_size" delta="100000" />
                <discovered_dataset designation="pca2" file="hicPCA/pca2_test3.bw" ftype="bigwig" compare="sim_size" delta="100000" />
            </output>

            <output name="pearson_outfile" ftype="h5">
                <assert_contents>
                    <has_h5_keys keys="intervals,matrix" />
                </assert_contents>
            </output>
            <output name="obsexp_outfile" ftype="h5">
                <assert_contents>
                    <has_h5_keys keys="intervals,matrix" />
                </assert_contents>
            </output>
        </test>
    </tests>
    <help><![CDATA[

Principal component analysis
============================

`Lieberman-Aiden et al. (2009)`_ demonstrated that open and closed chromatin domains throughout the genome occupy different spatial compartments in the nucleus, defined as A (activate) and B (inactive) compartments.

**hicPCA** computes two eigenvector files based on the input matrix for an A / B compartment analysis following the computation steps detailed by `Lieberman-Aiden et al. (2009)`_: the transformation of the contact matrix
into an observed vs. expected matrix and consecutively a Pearson correlation matrix shows a plaid pattern. These plaid pattern are called A and B. Applying a PCA on the obs/exp matrix gives the eigenvectors
and Lieberman-Aiden shows that the values of the eigenvectors correspond to the distribution of genes and with features of open and closed chromatin. In some cases the first principal component corresponds to the two
chromosomes arms and the second eigenvector to the plaid pattern. Therefore always the first two principal components needs to be returned and investigated.

_________________

Usage
-----

This tool must be used on Hi-C contact matrices with large bins (over 20kb) using ``hicMergeMatrixBins`` and corrected with ``hicCorrectMatrix``. Using matrices with a too high resolution (small bins or at restriction enzyme resolution) might take several days to run (even with over 100 CPU) or will fail due to memory limitations.

_________________

Output
------
Two files are outputed by **hicPCA**, one with the first (pca1) and one with the second (pca2) eigenvector as bigwig or bedgraph. These files can be plotted alongside Hi-C heatmaps, gene density or external datasets such as open chromatin or histone marks enrichment using ``pyGenomeTracks`` or ``hicPlotMatrix``.

For example, below you can find a ``hicPlotMatrix`` of the Pearson correlation matrix derived from a contact matrix for chromosome 6 in mouse computed with ``hicTransform`` (which is part of A/B compartments computation). The optional data track at the bottom shows the first eigenvector for A/B compartment obtained using **hicPCA**.

.. image:: $PATH_TO_IMAGES/hicPCA.png
   :scale: 35 %

_________________

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

.. _readthedocs.io: http://hicexplorer.readthedocs.io/en/latest/index.html
.. _`Lieberman-Aiden et al. (2009)`: https://pubmed.ncbi.nlm.nih.gov/19815776/
]]>    </help>
    <expand macro="citations" />
</tool>