changeset 7:c14ba4629233 draft

planemo upload for repository https://github.com/maxplanck-ie/HiCExplorer/tree/master/galaxy/wrapper/ commit eec0a4d5a7c5ba4ec0fbd2ead8280c3d143bb9d8
author iuc
date Fri, 27 Apr 2018 03:38:09 -0400
parents 8926550196ce
children 18737f03d581
files hicMergeMatrixBins.xml involucro macros.xml macros.xml.orig static/images/hicAggregateContacts.png static/images/hicCompareMatrices_QC_log2_m50_matrix_plot (1).png static/images/hicCompareMatrices_m1bp_over_gst_log2_m50_matrix_plot (1).png static/images/hicCorrelate_Dmel_heatmap.png static/images/hicCorrelate_Dmel_scatterplot.png static/images/hicMergeMatrixBins_Xchr.png static/images/hicMergeMatrixBins_Xregion.png static/images/hicPCA.png static/images/hicPlotDistvsCounts.png static/images/hicPlotMatrix.png static/images/hicPlotTADs.png static/images/hicQC_distance.png static/images/hicQC_pairs_discarded.png static/images/hicQC_pairs_sequenced.png static/images/hicQC_read_orientation.png static/images/hicQC_unmappable_and_non_unique.png static/images/pulication_plots_viewpoint.png test-data/compare_matrices_log2ratio.h5 test-data/compare_matrices_pearson_ratio.cool test-data/covariance_small_50kb.cool test-data/covariance_small_50kb.h5 test-data/hicCorrectMatrix_result1.npz.h5 test-data/hicMergeMatrixBins_result1.npz.h5 test-data/hicPlotDistVsCounts_result2.png test-data/hicSumMatrices_result1.npz.h5 test-data/li_viewpoint_32-33Mb.png test-data/li_viewpoint_32Mb.png test-data/multiFDR_zscore_matrix.h5 test-data/obs_exp_small_50kb.cool test-data/obs_exp_small_50kb.h5 test-data/pca1.bw test-data/pearson_small_50kb.h5 test-data/pearson_small_50kb_transform.cool test-data/small_matrix_50kb_pearson_pca1_plot.svg test-data/small_test_matrix_2.h5
diffstat 39 files changed, 24343 insertions(+), 24909 deletions(-) [+]
line wrap: on
line diff
--- a/hicMergeMatrixBins.xml	Wed Mar 07 03:45:11 2018 -0500
+++ b/hicMergeMatrixBins.xml	Fri Apr 27 03:38:09 2018 -0400
@@ -1,5 +1,5 @@
 <tool id="hicexplorer_hicmergematrixbins" name="@BINARY@" version="@WRAPPER_VERSION@.0">
-    <description>Merges bins from a Hi-C matrix</description>
+    <description>merge adjacent bins from a Hi-C contact matrix to reduce its resolution</description>
     <macros>
         <token name="@BINARY@">hicMergeMatrixBins</token>
         <import>macros.xml</import>
@@ -19,7 +19,7 @@
         <expand macro='matrix_h5_cooler_macro' />
 
         <param argument="--numBins" type="integer" min="1" value="3" label="Number of bins to merge" />
-        <param argument="--runningWindow" type="boolean" falsevalue="" truevalue="--runningWindow" label="Merge using a running window of length --numBins" />
+        <param argument="--runningWindow" type="boolean" falsevalue="" truevalue="--runningWindow" label="Set to merge for using a running window of length --numBins. Usually not set." />
         <param name='outputFormat' type='select' label="Output file format">
             <option value='h5' selected='true'>HiCExplorer format</option>
             <option value="cool">cool</option>
@@ -44,31 +44,51 @@
 Change matrix resolution
 ========================
 
-``hicMergeMatrixBins`` is used to decrease the resolution of a matrix. With this tool you can create out of a 100 kb 
+**hicMergeMatrixBins** is used to decrease the resolution of a matrix. With this tool, you can for example create out of a 100 kb
 contact matrix a 1000 kb one:
 
 Number of bins to merge = 10
 
 100 kb * 10 = 1000 kb = 1 Mb
 
-This functionality is useful especially for plotting. The higher the resolution of an contact matrix is, the more likely it is
-to run out of memory while plotting. This is caused by the circumstances that we compute internally with a sparse matrices but 
-to plot we need a dense one. Furthermore, the higher the resolution of a matrix the more detailed it is which can make it 
-difficult to interpret, especially if the read depth of the Hi-C data is not high.
+Depending on the downstream analyses to perform on a Hi-C matrix generated with HiCExplorer, one might need different bin resolutions. For example using ``hicPlotMatrix`` to display chromatin interactions of a whole chromosome will not produce any meaningful vizualisation if it is performed on a matrix at restriction sites resolution (unmerged). Furthermore, the higher the resolution of a matrix, the more detailed it is, which can make it
+difficult to interpret, especially if the read depth of the Hi-C data is not high enough. **hicMergeMatrixBins** address these issues by merging a given number of adjacent bins to reduce Hi-C matrices resolution.
 
-Input
+_________________
+
+Usage
 -----
 
-Parameters
-__________
-- contact matrix to change the resolution on
-- Number of bins to merge
-- running window
+To limit the loss of information, it is mandatory to perform **hicMergeMatrixBins** on matrices prior to any correction and any other bin merging (direct output from ``hicBuildMatrix``). After bin merging, ``hicCorrectMatrix`` must be used for downstream analyses requiring corrected matrices.
+
+_________________
 
 Output
 ------
 
-A contact matrix with the resolution ``original resolution * number of bins``.
+**hicMergeMatrixBins** outputs a Hi-C matrix with reduced resolution.
+
+Below, we will develop the example of a Hi-C matrix in *Drosophila melanogaster* that we want to display at the whole X-chromosome scale and at the scale of a 1Mb region of the X chromosome. To do this, we performed two different bin merging using **hicMergeMatrixBins** on an uncorrected matrix built at the restiction sites resolution using ``hicBuildMatrix``.
+
+Starting from a matrix with bins of a median length of 529bp (restriction enzyme resolution, here DpnII), running **hicMergeMatrixBins** with a number of bins to merge of 3 produced a matrix with bins of a median length of 1661bp, while **hicMergeMatrixBins** with a number of bins to merge of 50 produced a matrix with bins of a median length of 29798bp.
+
+After the correction of these three matrices using ``hicCorrectMatrix``, we plotted them using ``hicPlotMatrix`` at the scale of the whole X-chromosome and at the scale of the X:2000000-3000000 region to see the effect of bin merging on the interactions visualization.
+
+- **Effect of bins merging at the scale of a chromosome:**
+
+.. image:: $PATH_TO_IMAGES/hicMergeMatrixBins_Xchr.png
+   :width: 60 %
+
+When observed altogether, the plots above show that the merging of bins by 50 is the most adequate way to plot interactions for a whole chromosome in *Drosophila melanogaster* when starting from a matrix with bins of a median length of 529bp.
+
+- **Effect of bins merging at the scale of a specific region:**
+
+.. image:: $PATH_TO_IMAGES/hicMergeMatrixBins_Xregion.png
+   :width: 60 %
+
+When observed altogether, the plots above show that the merging of bins by 3 is the most adequate way to plot interactions for a region of 1Mb in Drosophila melanogaster when starting from a matrix with bins of a median length of 529bp.
+
+_________________
 
 | For more information about HiCExplorer please consider our documentation on readthedocs.io_
 
Binary file involucro has changed
--- a/macros.xml	Wed Mar 07 03:45:11 2018 -0500
+++ b/macros.xml	Fri Apr 27 03:38:09 2018 -0400
@@ -1,7 +1,6 @@
 <macros>
     <token name="@THREADS@">\${GALAXY_SLOTS:-4}</token>
-    <token name="@WRAPPER_VERSION@">2.1</token>
-
+    <token name="@WRAPPER_VERSION@">2.1.2</token>
     <token name="@USE_RANGE@">
         #if $use_range.select_use_range == "yes_use_range":
             --range $range_min:$range_max
@@ -28,7 +27,7 @@
     </xml>
     <xml name="use_range">
         <conditional name="use_range"> <!-- argparse specifies one argument of type min_range:max_range -->
-            <param name="select_use_range" type="select" label="Range restriction (in bp)" argument="--range">
+            <param name="select_use_range" type="select" label="Range restriction (in bp)" argument="--range" help="If given, only counts within the specified range are considered.">
                 <option value="no_use_range">No restriction</option>
                 <option value="yes_use_range">Only consider counts within a range</option>
             </param>
@@ -40,8 +39,8 @@
     </xml>
 
     <xml name="range">
-        <param name="range_min" type="integer" value="" min="0"/>
-        <param name="range_max" type="integer" value="" min="0"/>
+        <param name='range_min' label="Minimum range to consider interactions" type="integer" value="" min="0" help="The minimum range should be farer from the diagonal than median TAD size in order to reduce background interactions."/>
+        <param name='range_max' label="Maximum range to consider interactions" type="integer" value="" min="0"/>
     </xml>
 
     <xml name="colormap">
@@ -189,9 +188,9 @@
 
 
     <xml name="multiple_input_matrices">
-        <repeat name="input_files" title="HiC Matrix files" min="2">
+        <repeat name="input_files" title="Hi-C Matrix files" min="2">
             <param name="matrix" type="data" format="h5,cool"
-                label="HiC Matrix file"
+                label="Hi-C Matrix file"
                 help=""/>
             <param name="mlabel" type="text" size="30" optional="true" value=""
                 label="Label"
--- a/macros.xml.orig	Wed Mar 07 03:45:11 2018 -0500
+++ /dev/null	Thu Jan 01 00:00:00 1970 +0000
@@ -1,585 +0,0 @@
-<macros>
-    <token name="@THREADS@">\${GALAXY_SLOTS:-4}</token>
-<<<<<<< HEAD
-    <token name="@WRAPPER_VERSION@">2.0</token>
-
-    <token name="@USE_RANGE@">
-        #if $use_range.select_use_range == "yes_use_range":
-            --range $range_min:$range_max
-        #end if
-    </token>
-
-=======
-    <token name="@WRAPPER_VERSION@">2.1alpha1</token>
->>>>>>> joachimwolff-master
-    <xml name="requirements">
-        <requirements>
-            <requirement type="package" version="@WRAPPER_VERSION@">hicexplorer</requirement>
-            <yield />
-        </requirements>
-        <version_command>@BINARY@ --version</version_command>
-    </xml>
-
-    <xml name="citations">
-        <citations>
-            <citation type="doi">10.5281/zenodo.1133705</citation>
-            <yield />
-        </citations>
-    </xml>
-
-    <xml name="zMax">
-        <param argument="--zMax" name="zMax" type="float" optional="true" label="zMax for 3D plot"/> <!-- this should only be enabled when both or 3d is selected for param whatToShow -->
-    </xml>
-    <xml name="use_range">
-        <conditional name="use_range"> <!-- argparse specifies one argument of type min_range:max_range -->
-            <param name="select_use_range" type="select" label="Range restriction (in bp)" argument="--range">
-                <option value="no_use_range">No restriction</option>
-                <option value="yes_use_range">Only consider counts within a range</option>
-            </param>
-            <when value="no_use_range"/>
-            <when value="yes_use_range">
-                <param name="range_min" type="integer" value="" min="0"/>
-                <param name="range_max" type="integer" value="" min="0"/>
-            </when>
-        </conditional>
-    </xml>
-    <xml name="colormap">
-        <param argument="--colorMap" name="colormap" type="select" optional="True" label="Color map to use for the heatmap" help=" Available color map names can be found here: https://matplotlib.org/examples/color/colormaps_reference.html">
-            <option value="RdYlBu">RdYlBu</option>
-            <option value="Accent">Accent</option>
-            <option value="Spectral">Spectral</option>
-            <option value="Set1">Set1</option>
-            <option value="Set2">Set2</option>
-            <option value="Set3">Set3</option>
-            <option value="Dark2">Dark2</option>
-            <option value="Reds">Reds</option>
-            <option value="Oranges">Oranges</option>
-            <option value="Greens">Greens</option>
-            <option value="Blues">Blues</option>
-            <option value="Greys">Greys</option>
-            <option value="Purples">Purples</option>
-            <option value="Paired">Paired</option>
-            <option value="Pastel1">Pastel1</option>
-            <option value="Pastel2">Pastel2</option>
-            <option value="spring">spring</option>
-            <option value="summer">summer</option>
-            <option value="autumn">autumn</option>
-            <option value="winter">winter</option>
-            <option value="hot">hot</option>
-            <option value="coolwarm">coolwarm</option>
-            <option value="cool">cool</option>
-            <option value="seismic">seismic</option>
-            <option value="terrain">terrain</option>
-            <option value="ocean">ocean</option>
-            <option value="rainbow">rainbow</option>
-            <option value="bone">bone</option>
-            <option value="flag">flag</option>
-            <option value="prism">prism</option>
-            <option value="cubehelix">cubehelix</option>
-            <option value="binary">binary</option>
-            <option value="pink">pink</option>
-            <option value="gray">gray</option>
-            <option value="copper">copper</option>
-            <option value="BrBG">BrBG</option>
-            <option value="BuGn">BuGn</option>
-            <option value="BuPu">BuPu</option>
-            <option value="GnBu">GnBu</option>
-            <option value="OrRd">OrRd</option>
-            <option value="PiYG">PiYG</option>
-            <option value="PRGn">PRGn</option>
-            <option value="PuOr">PuOr</option>
-            <option value="PuRd">PuRd</option>
-            <option value="PuBu">PuBu</option>
-            <option value="RdBu">RdBu</option>
-            <option value="RdGy">RdGy</option>
-            <option value="RdPu">RdPu</option>
-            <option value="YlGn">YlGn</option>
-            <option value="PuBuGn">PuBuGn</option>
-            <option value="RdYlGn">RdYlGn</option>
-            <option value="YlGnBu">YlGnBu</option>
-            <option value="YlOrBr">YlOrBr</option>
-            <option value="YlOrRd">YlOrRd</option>
-            <option value="gist_gray">gist_gray</option>
-            <option value="gist_stern">gist_stern</option>
-            <option value="gist_earth">gist_earth</option>
-            <option value="gist_yarg">gist_yarg</option>
-            <option value="gist_ncar">gist_ncar</option>
-            <option value="gist_rainbow">gist_rainbow</option>
-            <option value="gist_heat">gist_heat</option>
-            <option value="gnuplot">gnuplot</option>
-            <option value="gnuplot2">gnuplot2</option>
-            <option value="CMRmap">CMRmap</option>
-            <option value="bwr">bwr</option>
-            <option value="hsv">hsv</option>
-            <option value="brg">brg</option>
-            <option value="jet">jet</option>
-            <option value="afmhot">afmhot</option>
-            <option value="Accent_r">Accent reversed</option>
-            <option value="Spectral_r">Spectral reversed</option>
-            <option value="Set1_r">Set1 reversed</option>
-            <option value="Set2_r">Set2 reversed</option>
-            <option value="Set3_r">Set3 reversed</option>
-            <option value="Dark2_r">Dark2 reversed</option>
-            <option value="Reds_r">Reds reversed</option>
-            <option value="Oranges_r">Oranges reversed</option>
-            <option value="Greens_r">Greens reversed</option>
-            <option value="Blues_r">Blues reversed</option>
-            <option value="Greys_r">Greys reversed</option>
-            <option value="Purples_r">Purples reversed</option>
-            <option value="Paired_r">Paired reversed</option>
-            <option value="Pastel1_r">Pastel1 reversed</option>
-            <option value="Pastel2_r">Pastel2 reversed</option>
-            <option value="spring_r">spring reversed</option>
-            <option value="summer_r">summer reversed</option>
-            <option value="autumn_r">autumn reversed</option>
-            <option value="winter_r">winter reversed</option>
-            <option value="hot_r">hot reversed</option>
-            <option value="coolwarm_r">coolwarm reversed</option>
-            <option value="cool_r">cool reversed</option>
-            <option value="seismic_r">seismic reversed</option>
-            <option value="terrain_r">terrain reversed</option>
-            <option value="ocean_r">ocean reversed</option>
-            <option value="rainbow_r">rainbow reversed</option>
-            <option value="bone_r">bone reversed</option>
-            <option value="flag_r">flag reversed</option>
-            <option value="prism_r">prism reversed</option>
-            <option value="cubehelix_r">cubehelix reversed</option>
-            <option value="binary_r">binary reversed</option>
-            <option value="pink_r">pink reversed</option>
-            <option value="gray_r">gray reversed</option>
-            <option value="copper_r">copper reversed</option>
-            <option value="BrBG_r">BrBG reversed</option>
-            <option value="BuGn_r">BuGn reversed</option>
-            <option value="BuPu_r">BuPu reversed</option>
-            <option value="GnBu_r">GnBu reversed</option>
-            <option value="OrRd_r">OrRd reversed</option>
-            <option value="PiYG_r">PiYG reversed</option>
-            <option value="PRGn_r">PRGn reversed</option>
-            <option value="PuOr_r">PuOr reversed</option>
-            <option value="PuRd_r">PuRd reversed</option>
-            <option value="PuBu_r">PuBu reversed</option>
-            <option value="RdBu_r">RdBu reversed</option>
-            <option value="RdGy_r">RdGy reversed</option>
-            <option value="RdPu_r">RdPu reversed</option>
-            <option value="YlGn_r">YlGn reversed</option>
-            <option value="PuBuGn_r">PuBuGn reversed</option>
-            <option value="RdYlBu_r" selected="True">RdYlBu reversed</option>
-            <option value="RdYlGn_r">RdYlGn reversed</option>
-            <option value="YlGnBu_r">YlGnBu reversed</option>
-            <option value="YlOrBr_r">YlOrBr reversed</option>
-            <option value="YlOrRd_r">YlOrRd reversed</option>
-            <option value="gist_gray_r">gist_gray reversed</option>
-            <option value="gist_stern_r">gist_stern reversed</option>
-            <option value="gist_earth_r">gist_earth reversed</option>
-            <option value="gist_yarg_r">gist_yarg reversed</option>
-            <option value="gist_ncar_r">gist_ncar reversed</option>
-            <option value="gist_rainbow_r">gist_rainbow reversed</option>
-            <option value="gist_heat_r">gist_heat reversed</option>
-            <option value="gnuplot_r">gnuplot reversed</option>
-            <option value="gnuplot2_r">gnuplot2 reversed</option>
-            <option value="CMRmap_r">CMRmap reversed</option>
-            <option value="bwr_r">bwr reversed</option>
-            <option value="hsv_r">hsv reversed</option>
-            <option value="brg_r">brg reversed</option>
-            <option value="jet_r">jet reversed</option>
-            <option value="afmhot_r">afmhot reversed</option>
-        </param>
-    </xml>
-
-
-    <xml name="multiple_input_matrices">
-        <repeat name="input_files" title="HiC Matrix files" min="2">
-            <param name="matrix" type="data" format="h5,cool"
-                label="HiC Matrix file"
-                help=""/>
-            <param name="mlabel" type="text" size="30" optional="true" value=""
-                label="Label"
-                help="Label to use in the output. If not given the dataset name will be used instead."/>
-        </repeat>
-    </xml>
-
-    <token name="@multiple_input_matrices@">
-        #set $matrices = []
-        #set $mlabels = []
-        #for $counter, $i in enumerate($input_files):
-            ln -s $i.matrix #echo str($counter)+'_matrix'#;
-            #silent $matrices.append( '%s_matrix' % $counter )
-
-            #if str($i.mlabel.value) != "":
-                #set $mlabels += ['"%s"' % ($i.mlabel.value)]
-            #else
-                #set $mlabels += ['"%s"' % ($i.matrix.name)]
-            #end if
-        #end for
-        #set $mlabels = ' '.join($mlabels)
-        #set $matrices = ' '.join($matrices)
-    </token>
-
-
-    <xml name="region">
-        <param name="region" type="text" label="Region of the genome to limit the operation"
-            help="The format is chr:start-end. Also valid is just to specify a chromosome, for example chr10:10-500" argument="--region"/>
-    </xml>
-
-
-
-    <xml name="kmeans_clustering">
-        <conditional name="used_multiple_regions">
-            <param name="used_multiple_regions_options" type="select"
-                label="Did you compute the matrix with more than one groups of regions?"
-                help="Would you like to cluster the regions according to the similarity of the signal distribution? This is only possible if you used computeMatrix on only one group of regions.">
-                <option value="yes">Yes, I used multiple groups of regions</option>
-                <option value="no">No, I used only one group</option>
-            </param>
-            <when value="no">
-                <conditional name="clustering">
-                    <param name="clustering_options" type="select" label="Clustering algorithm">
-                        <option value="none">No clustering</option>
-                        <option value="kmeans">Kmeans clustering</option>
-                    </param>
-                    <when value="kmeans">
-                        <param name="k_kmeans" type="integer" value="0" label="Number of clusters to compute"
-                            help="When this option is set, then the matrix is split into clusters using the kmeans algorithm. Only works for data that is not grouped, otherwise only the first group will be clustered. If more specific clustering methods are required it is advisable to save the underlying matrix and run the clustering using other software. The plotting of the clustering may fail (Error: Segmentation fault) if a cluster has very few members compared to the total number or regions. (default: None)."/>
-                    </when>
-                    <when value="none" />
-                </conditional>
-            </when>
-            <when value="yes" />
-        </conditional>
-    </xml>
-
-    <token name="@KMEANS_CLUSTERING@">
-        #if $advancedOpt.used_multiple_regions.used_multiple_regions_options == 'no':
-            #if $advancedOpt.used_multiple_regions.clustering.clustering_options == 'kmeans':
-                #if int($advancedOpt.used_multiple_regions.clustering.k_kmeans) > 0:
-                    --kmeans $advancedOpt.used_multiple_regions.clustering.k_kmeans
-                #end if
-            #end if
-        #end if
-    </token>
-
-    <xml name="samFlag">
-        <param name="samFlag" type="integer" optional="true" value=""
-            label="Filter reads based on the SAM flag"
-            help= "For example to get only reads that are the first mate use a flag of 64. This is useful to count properly paired reads only once, otherwise the second mate will be also considered for the coverage. (--samFlag)"/>
-    </xml>
-    <xml name="plotNumbers">
-        <param name="plotNumbers" type="boolean" truevalue="--plotNumbers" falsevalue=""
-            label="Plot the correlation value"
-            help="If set, then the correlation number is plotted on top of the heatmap. (--plotNumbers)"/>
-    </xml>
-    <xml name="doNotExtendPairedEnds">
-        <param name="doNotExtendPairedEnds" type="boolean" truevalue="--doNotExtendPairedEnds" falsevalue=""
-            label="Do not extend paired ends"
-            help="If set, reads are not extended to match the fragment length reported in the BAM file, instead they will be extended to match the fragment length. Default is to extend the reads if paired end information is available. (--doNotExtendPairedEnds)"/>
-    </xml>
-
-    <xml name="ignoreDuplicates">
-        <param name="ignoreDuplicates" type="boolean" truevalue="--ignoreDuplicates" falsevalue=""
-            label="Ignore duplicates"
-            help="If set, reads that have the same orientation and start position will be considered only once. If reads are paired, the mate position also has to coincide to ignore a read. (--ignoreDuplicates)" />
-    </xml>
-
-    <xml name="minMappingQuality">
-        <param argument="--minMappingQuality" type="integer" optional="true" value="" min="1"
-            label="Minimum mapping quality"
-            help= "If set, only reads that have a mapping quality score higher than the given value are considered.
-                *Note* Bowtie's Mapping quality is related to uniqueness: the higher the score, the more unique is a read.
-                A mapping quality defined by Bowtie of 10 or less indicates that there is at least a 1 in 10 chance that the read truly originated elsewhere."/>
-    </xml>
-
-    <xml name="skipZeros">
-        <param name="skipZeros" type="boolean" truevalue="--skipZeros" falsevalue=""
-            label ="Skip zeros"
-            help  ="If set, then zero counts that happen for *all* BAM files given are ignored. This might have the effect that fewer regions are considered than indicated in the option where the number of samples is defined. (--skipZeros)" />
-    </xml>
-
-    <xml name="fragmentLength">
-        <param name="fragmentLength" type="integer" value="300" min="1"
-            label="Fragment length used for the sequencing"
-            help ="If paired-end reads are used, the fragment length is computed from the BAM file. (--fragmentLength)"/>
-    </xml>
-
-    <xml name="scaleFactor">
-        <param name="scaleFactor1" type="float" value="1" label="Scale factor for treatment" help="(--scaleFactors)"/>
-        <param name="scaleFactor2" type="float" value="1" label="Scale factor for input" help="(--scaleFactors)"/>
-    </xml>
-
-    <xml name="xMax">
-        <param argument="--xMax" name="xMax" type="integer" optional="true" value=""
-            label="Max value for the x-axis in counts per bin" />
-    </xml>
-
-    <xml name="filterThreshold">
-        <param argument="--filterThreshold" name="filterThreshold_low" type="float" value="-1.5"
-            label="Remove bins of low coverage" help="e.g. -1.5; Both Thresholds needs to be set to take effect."/>
-
-        <param argument="--filterThreshold" name="filterThreshold_large" type="float" value="5.0"
-            label="Remove bins of large coverage" help="e.g. 5; Both Thresholds needs to be set to take effect."/>
-    </xml>
-
-    <xml name="pseudocount">
-        <param name="pseudocount" type="float" value="1" label="Pseudocount" help="Small number to avoid dividing by zero."/>
-    </xml>
-    <xml name='matrix_h5_cooler_macro'>
-        <param name='matrix_h5_cooler' type="data" format="h5,cool"
-            label="Matrix to compute on"/>
-    </xml>
-    <xml name='matrix_h5_cooler_multiple_macro'>
-        <param name='matrix_h5_cooler_multiple' type="data" format="h5,cool"
-            label="Matricies to compute on" multiple="true"/>
-    </xml>
-    <token name="@REFERENCES@">
-
-.. class:: infomark
-
-For more information on the tools, please visit our `help site`_.
-
-If you would like to give us feedback or you run into any trouble, please send an email to deeptools@googlegroups.com
-
-This tool is developed by the `Bioinformatics and Deep-Sequencing Unit`_ at the `Max Planck Institute for Immunobiology and Epigenetics`_.
-
-.. _Bioinformatics and Deep-Sequencing Unit: http://www3.ie-freiburg.mpg.de/facilities/research-facilities/bioinformatics-and-deep-sequencing-unit/
-.. _Max Planck Institute for Immunobiology and Epigenetics: http://www3.ie-freiburg.mpg.de
-.. _help site: https://hicexplorer.readthedocs.org
-
-    </token>
-
-
-    <xml name="multiple_input_bams">
-        <repeat name="input_files" title="BAM files" min="2">
-            <param name="bamfile" type="data" format="bam"
-                label="Bam file"
-                help="The BAM file must be sorted."/>
-            <param name="label" type="text" size="30" optional="true" value=""
-                label="Label"
-                help="Label to use in the output. If not given the dataset name will be used instead."/>
-        </repeat>
-    </xml>
-
-    <xml name="multiple_input_bigwigs">
-        <repeat name="input_files" title="BigWig files" min="2">
-            <param name="bigwigfile" type="data" format="bigwig"
-                label="Bigwig file"
-                help="The Bigwig file must be sorted."/>
-            <param name="label" type="text" size="30" optional="true" value=""
-                label="Label"
-                help="Label to use in the output. If not given the dataset name will be used instead."/>
-        </repeat>
-    </xml>
-
-    <xml name="plotTitle">
-        <param name="plotTitle" type="text" value="" size="30" optional="True"
-            label="Title of the plot"
-            help="Title of the plot, to be printed on top of the generated image. (--plotTitle)" />
-    </xml>
-
-    <token name="@multiple_input_bams@">
-        #import tempfile
-        #set $temp_dir = os.path.abspath(tempfile.mkdtemp())
-        #set files=[]
-        #set labels=[]
-        #for $i in $input_files:
-            #set $temp_input_handle = tempfile.NamedTemporaryFile( dir=$temp_dir )
-            #set $temp_input_path = $temp_input_handle.name
-            #silent $temp_input_handle.close()
-            #silent os.system("ln -s %s %s.bam" % (str($i.bamfile), $temp_input_path))
-            #silent os.system("ln -s %s %s.bam.bai" % (str($i.bamfile.metadata.bam_index), $temp_input_path))
-            #silent $files.append('%s.bam' % $temp_input_path)
-
-            ##set $files += [str($i.bamfile)]
-            #if str($i.label.value) != "":
-                #set $labels += ["\"%s\"" % ($i.label.value)]
-            #else
-                #set $labels += ["\"%s\"" % ($i.bamfile.name)]
-            #end if
-        #end for
-    </token>
-
-    <token name="@multiple_input_bigwigs@">
-        #import tempfile
-        #set $temp_dir = os.path.abspath(tempfile.mkdtemp())
-        #set files=[]
-        #set labels=[]
-        #for $i in $input_files:
-            #set $temp_input_handle = tempfile.NamedTemporaryFile( dir=$temp_dir )
-            #set $temp_input_path = $temp_input_handle.name
-            #silent $temp_input_handle.close()
-            #silent os.system("ln -s %s %s.bw" % (str($i.bigwigfile), $temp_input_path))
-            #silent $files.append('%s.bw' % $temp_input_path)
-
-            ##set $files += [str($i.bigwigfile)]
-            #if str($i.label.value) != "":
-                #set $labels += ["\"%s\"" % ($i.label.value)]
-            #else
-                #set $labels += ["\"%s\"" % ($i.bigwigfile.name)]
-            #end if
-        #end for
-    </token>
-
-    <xml name="reference_genome_source">
-        <conditional name="source">
-            <param name="ref_source" type="select" label="Reference genome">
-                <option value="cached">locally cached</option>
-                <option value="history">in your history</option>
-            </param>
-            <when value="cached">
-                <param name="input1_2bit" type="select" label="Using reference genome" help="If your genome of interest is not listed, contact the Galaxy team">
-                    <options from_data_table="deepTools_seqs">
-                        <filter type="sort_by" column="1" />
-                        <validator type="no_options" message="No indexes are available." />
-                    </options>
-                </param>
-            </when>
-            <when value="history">
-                <param name="input1" type="data" format="twobit" label="Select a reference dataset in 2bit format" />
-            </when>
-        </conditional>
-    </xml>
-
-    <token name="@reference_genome_source@">
-    #if $source.ref_source=="history":
-        --genome $source.input1
-    #else:
-        --genome "${source.input1_2bit.fields.path}"
-    #end if
-    </token>
-
-    <xml name="effectiveGenomeSize">
-        <conditional name="effectiveGenomeSize">
-            <param name="effectiveGenomeSize_opt" type="select" label="Effective genome size"
-                help="The effective genome size is the portion of the genome that is mappable. Large fractions of the genome are stretches of NNNN that should be discarded.
-                    Also, if repetitive regions were not included in the mapping of reads, the effective genome size needs to be adjusted accordingly.
-                    See Table 2 of http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030377 or http://www.nature.com/nbt/journal/v27/n1/fig_tab/nbt.1518_T1.html for several effective genome sizes.">
-                <option value="93260000">ce10 (93260000)</option>
-                <option value="121400000">dm3 (121400000)</option>
-                <option value="2451960000" selected="true">hg19 (2451960000)</option>
-                <option value="2150570000">mm9 (2150570000)</option>
-                <option value="specific">user specified</option>
-            </param>
-            <when value="specific">
-                <param name="effectiveGenomeSize" type="integer" value="" label="Effective genome size" help="e.g. ce10: 93260000, dm3: 121400000, hg19: 2451960000, mm9: 2150570000"/>
-            </when>
-            <when value="2150570000" />
-            <when value="2451960000" />
-            <when value="121400000" />
-            <when value="93260000" />
-        </conditional>
-    </xml>
-
-    <xml name="image_file_format">
-        <param name="outFileFormat" type="select" label="Image file format">
-            <option value="png" selected="true">png</option>
-            <option value="pdf">pdf</option>
-            <option value="svg">svg</option>
-            <option value="eps">eps</option>
-            <option value="emf">emf</option>
-        </param>
-    </xml>
-
-    <xml name="missingDataAsZero">
-                <param name="missingDataAsZero" type="boolean" truevalue="yes" falsevalue="no" checked="True"
-                    label ="Treat missing data as zero"
-                    help  ="This parameter determines if missing data should be treated as zeros. If unchecked, missing data will be ignored and not included in the output file. Missing data is defined as those regions for which both BAM files have 0 reads." />
-    </xml>
-
-    <xml name="input_save_matrix_values">
-        <param name="saveMatrix" type="boolean" label="Save the matrix of values underlying the heatmap"/>
-    </xml>
-
-    <xml name="input_graphic_output_settings">
-        <conditional name="output" >
-            <param name="showOutputSettings" type="select" label="Show advanced output settings" >
-                <option value="no" selected="true">no</option>
-                <option value="yes">yes</option>
-            </param>
-            <when value="no" />
-            <when value="yes">
-                <yield />
-                <param name="saveData" type="boolean" label="Save the data underlying the average profile"/>
-                <param name="saveSortedRegions" type="boolean" label="Save the regions after skipping zeros or min/max threshold values" help="The order of the regions in the file follows the sorting order selected. This is useful, for example, to generate other heatmaps keeping the sorting of the first heatmap."/>
-            </when>
-        </conditional>
-    </xml>
-
-    <xml name="input_image_file_format">
-        <param name="outFileFormat" type="select" label="Image file format">
-            <option value="png" selected="true">png</option>
-            <option value="pdf">pdf</option>
-            <option value="svg">svg</option>
-            <option value="eps">eps</option>
-            <option value="emf">emf</option>
-        </param>
-    </xml>
-
-    <xml name="output_image_file_format">
-        <data format="png" name="outFileName" label="${tool.name} image">
-            <change_format>
-                <when input="output.outFileFormat" value="pdf" format="pdf" />
-                <when input="output.outFileFormat" value="svg" format="svg" />
-                <when input="output.outFileFormat" value="eps" format="eps" />
-                <when input="output.outFileFormat" value="emf" format="emf" />
-            </change_format>
-        </data>
-    </xml>
-
-    <xml name="output_save_matrix_values">
-        <data format="tabular" name="outFileNameMatrix" label="${tool.name} on ${on_string}: Heatmap values">
-            <filter>
-            ((
-                output['showOutputSettings'] == 'yes' and
-                output['saveMatrix'] is True
-            ))
-            </filter>
-        </data>
-    </xml>
-
-    <xml name="output_graphic_outputs">
-        <data format="tabular" name="outFileNameData" label="${tool.name} on ${on_string}: averages per matrix column">
-            <filter>
-            ((
-                output['showOutputSettings'] == 'yes' and
-                output['saveData'] is True
-            ))
-            </filter>
-        </data>
-        <data format="bed" name="outFileSortedRegions" label="${tool.name} on ${on_string}: sorted/filtered regions">
-            <filter>
-            ((
-                output['showOutputSettings'] == 'yes' and
-                output['saveSortedRegions'] is True
-            ))
-            </filter>
-        </data>
-    </xml>
-
-    <xml name="track_input_h5_macro">
-        <param name="track_input_h5" type="data" format="h5, cool" label="Track file h5 or cool format"/>
-    </xml>
-    <xml name="track_input_bed_macro">
-        <param name="track_input_bed" type="data" format="bed" label="Track file bed format"/>
-    </xml>
-    <xml name="track_input_bedgraph_macro">
-        <param name="track_input_bedgraph" type="data" format="bedgraph" label="Track file bedgraph format"/>
-    </xml>
-    <xml name="track_input_bigwig_macro">
-        <param name="track_input_bigwig" type="data" format="bigwig" label="Track file bigwig format"/>
-    </xml>
-    <xml name="track_input_bedgraph_matrix_macro">
-        <param name="track_input_bedgraph_matrix" type="data" format="bedgraph" label="Track file bigwig format"/>
-    </xml>
-    <xml name="track_input_tabular_macro">
-        <param name="track_input_tabular" type="data" format="tabular" label="Track file tabular format"/>
-    </xml>
-    <xml name="plot_title">
-        <param name="title" type="text" optional="true" label="Plot title"/>
-    </xml>
-
-    <xml name="spacer_macro">
-        <param name="spacer_width" type="float" value="" optional="True"
-              label="Include spacer at the end of the track." help="Width of the spacer." />
-    </xml>
-    <xml name="fontsize_macro">
-        <param name="fontsize" type="integer" value="" optional="True" label="Fontsize" />
-    </xml>
-</macros>
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--- a/test-data/small_matrix_50kb_pearson_pca1_plot.svg	Wed Mar 07 03:45:11 2018 -0500
+++ b/test-data/small_matrix_50kb_pearson_pca1_plot.svg	Fri Apr 27 03:38:09 2018 -0400
@@ -19,25 +19,25 @@
   </g>
   <g id="axes_1">
    <g id="patch_2">
-    <path d="M 78.425 350.781389 
-L 380.762475 350.781389 
-L 380.762475 65.420504 
-L 78.425 65.420504 
+    <path d="M 78.675 350.879598 
+L 380.736238 350.879598 
+L 380.736238 65.685669 
+L 78.675 65.685669 
 z
 " style="fill:#ffffff;"/>
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-      <g transform="translate(72.556889 57.195527)rotate(-45)scale(0.0833 -0.0833)">
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" 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