<tool id="MaREA" name="Metabolic Reaction Enrichment Analysis" version="1.1.2">
	<macros>
		<import>marea_macros.xml</import>
	</macros>
	<requirements>
		<requirement type="package" version="0.23.0">pandas</requirement>
		<requirement type="package" version="1.1.0">scipy</requirement>
		<requirement type="package" version="0.10.1">cobra</requirement>
		<requirement type="package" version="4.2.1">lxml</requirement>
		<requirement type="package" version="0.8.1">svglib</requirement>
		<requirement type="package" version="3.4.0">reportlab</requirement>
	</requirements>
	<command detect_errors="exit_code">
		<![CDATA[
      	python $__tool_directory__/marea.py

      	--tool_dir $__tool_directory__
      	--option $cond.type_selector
        --out_log $log		
	
        #if $cond.type_selector == 'datasets':
            --input_datas
            #for $data in $cond.input_Datasets:
                ${data.input}
            #end for
            --names
            #for $data in $cond.input_Datasets:
                ${data.input_name}
            #end for
            --comparison ${cond.comparis.comparison}
            #if ${cond.advanced.cond_map.cond_map_choice} == 'true':
            	--custom_rules true
            	--custom_map ${cond.advanced.cond_map.custom_map}
            #end if
            #if $cond.advanced.choice == 'true':
      	       --pValue ${cond.advanced.pValue}
      	       --fChange ${cond.advanced.fChange}
	           --generate_svg ${cond.advanced.generateSvg}
	    	   --generate_pdf ${cond.advanced.generatePdf}
     	    #else 
	            --pValue 0.05
	            --fChange 1.5
	            --generate_svg false
	            --generate_pdf true
	            --generate_ras false
	        #end if
        #elif $cond.type_selector == 'dataset_class':
            --input_data ${input_data}
            --input_class ${input_class}
            --comparison ${cond.comparis.comparison}
            #if $cond.comparis.comparison == 'onevsmany'
            	--control ${cond.comparis.controlgroup}
            #end if
            #if $cond.advanced.cond_map.cond_map_choice == 'true':
            	--custom_rules true
            	--custom_map ${cond.advanced.cond_map.custom_map}
            #end if
            #if $cond.advanced.choice == 'true':
      	        --pValue ${cond.advanced.pValue}
      	        --fChange ${cond.advanced.fChange}
	            --generate_svg ${cond.advanced.generateSvg}
	            --generate_pdf ${cond.advanced.generatePdf}
	        #else 
	            --pValue 0.05
	            --fChange 1.5
	            --generate_svg false
	            --generate_pdf true
	        #end if
        #end if
        ]]>
	</command>
	<inputs>
		<conditional name="cond">
			<param name="type_selector" argument="--option" type="select" label="Input format:">
				<option value="datasets" selected="true">RAS of group 1 + RAS of group 2 + ... + RAS of group N</option>
				<option value="dataset_class">RAS of all samples + sample group specification</option>
			</param>
			<when value="datasets">
				<repeat name="input_Datasets" title="RAS dataset" min="2">
					<param name="input" argument="--input_datas" type="data" format="tabular, csv, tsv" label="add dataset" />
					<param name="input_name" argument="--names" type="text" label="Dataset's name:" value="Dataset" help="Default: Dataset" />
				</repeat>
				<conditional name="comparis">
					<param name="comparison" argument="--comparison" type="select" label="Groups comparison:">
						<option value="manyvsmany" selected="true">One vs One</option>
						<option value="onevsrest">One vs All</option>
						<option value="onevsmany">One vs Control</option>
					</param>
					<when value="onevsmany">
						<param name="controlgroup" argument="--controlgroup" type="text" label="Control group label:" value="0" help="Name of group label to be compared to others"/>
					</when>
				</conditional>
				<conditional name="advanced">
					<param name="choice" type="boolean" checked="false" label="Use advanced options?" help="Use this options to choose custom parameters for evaluation: pValue, Fold-Change threshold, how to solve (A and NaN) and specify output maps.">
						<option value="true" selected="true">No</option>
						<option value="false">Yes</option>
					</param>
					<when value="false"></when>
					<when value="true">
						<conditional name="cond_map">
						<param name="cond_map_choice" type="boolean" checked="false" label="Use custom map?" help="Use this option only if you have generated RAS using a custom set of rules">
							<option value="false" selected="true">No</option>
							<option value="true">Yes</option>
						</param>
						<when value="true">				
							<param name="Custom_map" argument="--custom_map" type="data" format="xml, svg" label="custom-map.svg"/>
						</when>
					</conditional>
						<param name="pValue" argument="--pValue" type="float" size="20" value="0.01" max="1" min="0" label="P-value threshold:" help="min value 0" />
						<param name="fChange" argument="--fChange" type="float" size="20" value="1.2" min="1" label="Fold-Change threshold:" help="min value 1" />
						<param name="generateSvg" argument="--generateSvg" type="boolean" checked="false" label="Generate SVG map" help="should the program generate an editable svg map of the processes?" />
						<param name="generatePdf" argument="--generatePdf" type="boolean" checked="true" label="Generate PDF map" help="should the program return a non editable (but displayble) pdf map of the processes?" />
					</when>
			</conditional>
			</when>
			<when value="dataset_class">
                <param name="input_data" argument="--input_data" type="data" format="tabular, csv, tsv" label="RAS of all samples" />
                <param name="input_class" argument="--input_class" type="data" format="tabular, csv, tsv" label="Sample group specification" />
                <conditional name="comparis">
					<param name="comparison" argument="--comparison" type="select" label="Groups comparison:">
						<option value="manyvsmany" selected="true">One vs One</option>
						<option value="onevsrest">One vs All</option>
						<option value="onevsmany">One vs Control</option>
					</param>
					<when value="onevsmany">
						<param name="controlgroup" argument="--controlgroup" type="text" label="Control group label:" value="0" help="Name of group label to be compared to others"/>
					</when>
				</conditional>
				<conditional name="advanced">
				<param name="choice" type="boolean" checked="false" label="Use advanced options?" help="Use this options to choose custom parameters for evaluation: pValue, Fold-Change threshold, how to solve (A and NaN) and specify output maps.">
					<option value="true" selected="true">No</option>
					<option value="false">Yes</option>
				</param>
				<when value="false"></when>
				<when value="true">
					<conditional name="cond_map">
						<param name="cond_map_choice" type="boolean" checked="false" label="Use custom map?" help="Use this option only if you have generated RAS using a custom set of rules">
							<option value="false" selected="true">No</option>
							<option value="true">Yes</option>
						</param>
						<when value="true">								
							<param name="custom_map" argument="--custom_map" type="data" format="xml, svg" label="custom-map.svg"/>
						</when>
					</conditional>
					<param name="pValue" argument="--pValue" type="float" size="20" value="0.01" max="1" min="0" label="P-value threshold:" help="min value 0" />
					<param name="fChange" argument="--fChange" type="float" size="20" value="1.2" min="1" label="Fold-Change threshold:" help="min value 1" />
					<param name="generateSvg" argument="--generateSvg" type="boolean" checked="false" label="Generate SVG map" help="should the program generate an editable svg map of the processes?" />
					<param name="generatePdf" argument="--generatePdf" type="boolean" checked="true" label="Generate PDF map" help="should the program return a non editable (but displayble) pdf map of the processes?" />
				</when>
			</conditional>
		</when>
	</conditional>
</inputs>
<outputs>
	<data format="txt" name="log" label="MaREA - Log" />
	<collection name="results" type="list" label="MaREA - Results">
		<discover_datasets pattern="__name_and_ext__" directory="result"/>
	</collection>
</outputs>
<help>
	<![CDATA[

What it does
-------------

This tool analyzes and visualizes differences in the Reaction Activity Scores (RASs) of groups of samples, as computed by the Expression2RAS tool, of groups of samples.

Accepted files are: 
    - option 1) two or more RAS datasets, each referring to samples in a given group. The user can specify a label for each group (as e.g. "classA" and "classB");
    - option 2) one RAS dataset and one group-file specifying the group each sample belongs to.
    
RAS datasets format: tab-separated text files, reporting the RAS value of each reaction (row) for a given sample (column).

Column header: sample ID.
Raw header: reaction ID. 

Optional files:
    - custom svg map. Graphical elements must have the same IDs of reactions. See HmrCore svg map for an example.

The tool generates:
    - 1) a tab-separated file: reporting fold-change and p-values of reaction activity scores (RASs) between a pair of conditions/classes;
    - 2) a metabolic map file (downloadable as .svg): visualizing up- and down-regulated reactions between a pair of conditions/classes;
    - 3) a log file (.txt).
    
Output options:
To calculate P-Values and Fold-Changes and to enrich maps, comparisons are performed for each possible pair of groups (default option ‘One vs One’).

Alternative options are:
    - comparison of each group vs. the rest of samples (option ‘One vs Rest’)
    - comparison of each group vs. a control group (option ‘One vs Control). If this option is selected the user must indicate the control group label.

Output files will be named as classA_vs_classB. Reactions will conventionally be reported as up-regulated (down-regulated) if they are significantly more (less) active in class having label "classA".

Example input
-------------

"RAS of group 1 + RAS of group 2 + ... + RAS of group N" option:

RAS Dataset 1:

+------------+----------------+----------------+----------------+ 
| Reaction ID|   TCGAA62670   |   TCGAA62671   |   TCGAA62672   |  
+============+================+================+================+
| r1642      |    0.523167    |    0.371355    |    0.925661    |  
+------------+----------------+----------------+----------------+    
| r1643      |    0.568765    |    0.765567    |    0.456789    |    
+------------+----------------+----------------+----------------+    
| r1640      |    0.876545    |    0.768933    |    0.987654    |  
+------------+----------------+----------------+----------------+
| r1641      |    0.456788    |    0.876543    |    0.876542    |    
+------------+----------------+----------------+----------------+    
| r1646      |    0.876543    |    0.786543    |    0.897654    |   
+------------+----------------+----------------+----------------+

RAS Dataset 2:

+------------+----------------+----------------+----------------+ 
| Reaction ID|   TCGAA62670   |   TCGAA62671   |   TCGAA62672   |  
+============+================+================+================+
| r1642      |    0.523167    |    0.371355    |    0.925661    |  
+------------+----------------+----------------+----------------+    
| r1643      |    0.568765    |    0.765567    |    0.456789    |    
+------------+----------------+----------------+----------------+    
| r1640      |    0.876545    |    0.768933    |    0.987654    |  
+------------+----------------+----------------+----------------+
| r1641      |    0.456788    |    0.876543    |    0.876542    |    
+------------+----------------+----------------+----------------+    
| r1646      |    0.876543    |    0.786543    |    0.897654    |   
+------------+----------------+----------------+----------------+

"RAS of all samples + sample group specification" option:

RAS Dataset:

+------------+----------------+----------------+----------------+ 
| Reaction ID|   TCGAA62670   |   TCGAA62671   |   TCGAA62672   |  
+============+================+================+================+
| r1642      |    0.523167    |    0.371355    |    0.925661    |  
+------------+----------------+----------------+----------------+    
| r1643      |    0.568765    |    0.765567    |    0.456789    |    
+------------+----------------+----------------+----------------+    
| r1640      |    0.876545    |    0.768933    |    0.987654    |  
+------------+----------------+----------------+----------------+
| r1641      |    0.456788    |    0.876543    |    0.876542    |    
+------------+----------------+----------------+----------------+    
| r1646      |    0.876543    |    0.786543    |    0.897654    |   
+------------+----------------+----------------+----------------+

Group-file

+---------------+-----------+
| Patient ID    |   Class   | 
+===============+===========+
| TCGAAA3529    |    MSI    | 
+---------------+-----------+  
| TCGAA62671    |    MSS    |    
+---------------+-----------+   
| TCGAA62672    |    MSI    |
+---------------+-----------+

Advanced options
----------------

P-Value threshold: the threshold used for significance Kolmogorov-Smirnov (KS) test, to verify whether the distributions of RASs over the samples in two sets are significantly different

Fold-Change threshold: threshold of the fold-change between the average RAS of two groups. Among the reactions that pass the KS test, only fold-change values larger than the indicated threshold will be visualized on the output metabolic map;


.. class:: infomark

**TIP**: If your data is not TAB delimited, use `Convert delimiters to TAB`_.

.. class:: infomark

**TIP**: If your dataset is not split into classes, use `MaREA cluster analysis`_.

@REFERENCE@

.. _MaREA: https://www.biorxiv.org/content/early/2018/01/16/248724
.. _Convert delimiters to TAB: https://usegalaxy.org/?tool_id=Convert+characters1&version=1.0.0&__identifer=6t22teyofhj
.. _MaREA cluster analysis: http://link del tool di cluster.org

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