<tool id="VINYL" name="VINYL" version="1">
  <description> VINYL, variant scoring. This module computes variants pathogenicity scores on annovar annotated vcf files</description>
  <requirements>
    <requirement type="package" >perl</requirement>
    <requirement type="package" >r-base</requirement>
  </requirements>
  <command> <![CDATA[
       ### call the .sh to untar the package 
	perl $__tool_directory__/score_complete_alt_M.pl -vcf $VcfFile  
	-disease_clinvar $score_DB -score_AF $score_RV -score_functional $score_FE -score_NS $score_NS 
	-score_nIND $score_OR -AF $AF -scoreeQTL $score_eQ -nind $nind -scoreG $score_AD -scoreT $score_T -scoreGW $score_GW -scoreR $score_R -scoreM $score_M -scoreSP $score_SP  -AD $AD -XL $XL
	
	#if $kfile	
	-keywords $kfile
	#else
	-keywords $__tool_directory__/kfile 
	#end if


	#if $efile
	-effects $efile
	#else
	-effects $__tool_directory__/efile
	#end if
	
	#if $qfile
	-leQTL $qfile
	#end if

	#if $disease
	-disease $disease
	#end if

	#if $similarD
	-similarD $similarD
	#end if

	#if $lgenes
	-lgenes $lgenes
	#end if

	-ofile $ofile 
	-ovcfile $ovcfile
	-osummary $osummary
        2>$log
##parametri di input:
##
##"vcf"=>"",              #file   mandatory, provided at runtime
##"disease"=>"",          #name   optional
##"similarD"=>"",         #file optional
##"lgenes"=>"",           #file optional
##"leQTL"=>"qfile",       #file   mandatory, but default value
##"keywords"=>"kfile",    #file   mandatory, but default value
##"effects"=>"efile",     #file   mandatory, but default value
##"disease_clinvar"=>8,   #numeric mandadory, but default value
##"score_AF"=>4,          #numeric mandatory, but default value
##"score_functional"=>8,  #numeric mandatory, but default value
##"score_NS"=>6,          #numeric mandatory, but default value
##"score_nIND"=>8,        #numeric mandatory, but default value
##"AF"=>0.0001,           #numeric mandatory, but default value
##"scoreeQTL"=>1,         #numeric mandatory, but default value
##"nind"=>5,              #numeric  mandatory, but default value
##"scoreG"=>2,            #numeric  mandatory, but default value 
    ]]>
  </command>
  <inputs>
    <param format="vcf" name="VcfFile" type="data" label="VCF" help="vcf input file"/>
<!-- default values-->
    <param name="score_DB" value="8" min="1" max="20" type="float" label="score_DB" help="Pathogenicity score component. The aggregate score is incremented by this value if variants are annotated as Pathogenic or Likely Pathogenic according to the Clinvar database. Subtracted for variants annotated as Benign or Likely Benign"/> 
    <param name="score_RV" value="4" min="1" max="20" type="float" label="score_RV" help="Allele Frequency score component. This value is addeded to the total pathogenicity score if the MAF of the variant according public databases of human genetic variants is lower or equal to the value indicated by the AF parameter"/> 
    <param name="score_FE" value="8" min="1" max="20" type="float" label="score_FE" help="Functional effect score component. For variants that have a predicted functional effect on the protein/mRNA, this score is added to the global pathogenicity score. Functional effects are indicated according to the Annovar annotation system. List of relevant functional effects are provided by the efile parameter  "/> 
    <param name="score_NS" value="6" min="1" max="20" type="float" label="score_NS" help="Disruptive NS score component. This value is summed to the global score if a non-synonymous variant is predicted to have a deleterious effect on the protein according to one or more tools for the prediction of the effect of NS variants (default CADD and Annovar). The score is subtracted if the variant is not deemed to be disruptive according to at least one tool. The list of methods that should be considered for the evaluation of the effect of NS variants is specified by the keywords file"/> 
    <param name="score_OR" value="8" min="1" max="20" type="float" label="score_OR" help="Over-representation score component. This value is added to the pathogenicity score if a variant that has a MAF&lt;=0.01 according to public databases of human genetic variation is observed in N or more individuals in the dataset. The value of N is specified by nind. As a rule of thumb N should be set to 5-10% of the size of your cohort of individuals" /> 
    <param name="score_eQ" value="1" min="1" max="20" type="float" label="score_eQ" help="eQTL score component. The global score is incremented by this value is a genetic variant is associated with expression Quantitative Trait Loci (eQTL) according to the GTEx database in a specific tissue. A list of (valid) tissues, according to the GTEx notation, can be provided by the qfile parameter  " /> 
   <param name="score_AD" value="2" min="1" max="20" type="float" label="score_AD" help="Disease Related Gene component of the score. This value is added to the score if variants are associated with genes that are known to be implicated in the diseases.  Users can (and are highly encouraged to) provide their list of disease associated genes by the means of the lgenes File"/>
    <param name="score_T" value="1" min="1"  max="20" type="float" label="score_T" help="Component of the score associated with SNPs that form a transcription factor binding site. This value is added to the global score if the underlying SNP is associated with a TFBS, according to the Ensembl regulatory build or the OregAnno database"/>
    <param name="score_M" value="1" min="1"  max="20" type="float" label="score_M" help="Component of the score associated with miRNA binding sites. This value is added to the global score if the underlying SNP is associated with a miRNA binding site, according to the Ensembl regulatory build or the OregAnno database"/>
    <param name="score_R" value="1" min="1"  max="20" type="float" label="score_R" help="Component of the score for SNPs that are incorporated whithin an annotated regulatory region . This value is added to the global score if the underlying SNP is part of an annotated regulatory region according to the Ensembl regulatory build or the OregAnno database"/>
    <param name="score_SP" value="1" min="1"  max="20" type="float" label="score_SP" help="Component of the score associated with SNPs predicted to have a disruptive effect on splice sites according to the dbscSNV database, version 1.1. This value is added to the global score for SNPs that are predicted to have a deleterious effect."/>
   <param name="score_GW" value="1" min="1"  max="20" type="float" label="score_GW" help="Component of the score associated with SNPs associated to a phenotypic trait relevant for the disease according to a Genome Wide Association Study (GWAS). This value is added to the cumulative score"/>
    <param name="AF" value="0.0001" min="0" max="1" type="float" label="AlleleFrequCutOff" help="Cut off value for the Allele frequency score. The value specified by scoreAF is addeded to the pathogenicity score only for variants that have an allele frequency lower or equal to this cut-off value " />
    <param name="nind" value="5" min="1" max="12" type="integer" label="Nind Cutoff" help="Cut off value for the Over-reprentation score. The value specified by scoreNind is addeded to the pathogenicity score only for variants that have an allele count in the cohort equal to or greater than this value. As a rule of tumb, this should be set to approximately 5-10% of the size of your cohort of individuals"/>
    <param name="AD" type="text" value="T" label="Autosomic Dominant" help="If set to T (TRUE) VYNIL assumes an Autosomic Dominant model of inherithance of the disease. If FALSE (F) the model is Autosomic Recessive.  Valid values are T=TRUE or F=FALSE Default is T"/>
    <param name="XL" type="text" value="F" label="X-linked" help="When T (TRUE) an X-linked model of Disease inheritance is used. Valid values are T=TRUE and F=FALSE. Default is FALSE" />
<!--optional values -->
    <param format="txt" name="kfile" type="data" optional="true" label="keywords file" help="This is a configuration file that specifies the keywords that are used by VINYL for the extraction of relevant annoations from the VCF file and for the computation of the pathogenicity score. Names of these keywords need to match exactly names as used by Annovar. A file with default values is incorporated in VINYL. Custom files can be provided (see Manual for the format)  "/>
    <param format="txt" name="efile" type="data" optional="true" label="Functional Effects files" help="This configuration file specifies the predicted functional effects for which the value specified by the functional score  parameter is added to the global pathogenicity score. See above for further explanations."/>
    <param format="txt" name="qfile" type="data" optional="true" label="eQTL file" help="This configuration file provides a list of tissues that are used by VINYL for the annotation of eQTL and the scoring of variants associated with eQTLs in those tissue. Names of tissues need  match names used in the GTEx project. See the manual for more details about the format of the file "/>
    <param name="disease" type="text" optional="true" label="Disease" help="Name or functional description of the pathological condition. This parameter is used to perform a soft check of the annotation in Clinvar and to identify variants that have been previously implicated in the disease. Highly recommended. Multiple names can be provided using # as a separator. For example cardiomyopathy#dilated specifies the 2 keywords: cardiomyopathy and dilated  "/>
    <param name="similarD" type="data" format="txt" optional="true" label="Symptoms" help="This file provides a list of symptoms or related keywords that are used by VINYL to screen the Annotations of Clinvar and identify variants that have been implicated in similar pathologies or phenotype. See the manual for a full description of the file format. User are strongly encouraged to provide this file "/>
    <param name="lgenes" type="data" format="txt" optional="true" label="List of Disease Genes" help="This file provides a list of genes that have been previously implicated in the disease of in similar pathological conditions. Users are highly recommended to provide this type of information. A full desciption of the format of this file is found in the VYNIL manual" />
<!--others-->

  </inputs>
  <outputs>
    <data format="txt" name="log" label="${tool.name} on ${on_string}: log file "/>
    <data format="tabular" name="ofile" label="${tool.name} on ${on_string}: tabular " help="Output file in tabular format with VINYL scores" />
    <data format="vcf" name="ovcfile" label="${tool.name} on ${on_string}: VCF " help="Output file in VCF format with VINYL scores"/>
    <data format="tabular" name="osummary" label="${tool.name} on ${on_string}: tabular " help="Output file in tabular format with detailed VINYL scores" />

  </outputs>
  <stdio>
  </stdio>
  <tests>
    <test>
      <param name="VcfFile" value="TSI_annotated.vcf" ftype="vcf" />
      <param name="lgenes" value="DCM_genes.tabular" ftype="tabular" />
      <param name="qfile" value="qfile.txt" ftype="txt" />
      <param name="kfile" value="kfile.txt" ftype="txt" />
      <param name="efile" value="efile.txt" ftype="txt" />
      <output name="ofile" file="VINYL_output1_test.tabular" ftype="tabular" />
      <output name="ovcfile" file="VINYL_output2_test.vcf" ftype="vcf" />
      <output name="osummary" file="VINYL_output3_test.tabular" ftype="tabular" />
      <output name="log" file="log.txt" ftype="txt" />
    </test>
  </tests>
  <help>
**What it does**
VINYL is a software designed to assist in variant prioritization in medium-large cohort of patients. The program computes an aggregate score, which is based on an extensive collection of publicly available annoations, in order to identify/prioritize variants that are likely to be pathogenic or have a clinical significance. In order to derive an optimal cut off score for the variants, VINYL uses a strategy based on "survival analysis", where the pathogenicity score distribution of the affected individuals is compared with a matched cohort of unaffected individuals.
To facilitate the usage of the software, VINYL is provided in the form of a public Galaxy instance, based on the Laniakea suite. To ensure the maximum level of security, VINYL uses Encrypted data volumes for the storage of the data.

**Important Usage Note**
This wrapper provides the module of VINYL that perform score calculation. See the "survival" and the "optimizer" utilities for the delineation of the cut-off score and the  optimization of the score components value
A complete workflow that automates the exectuion of VINYL is avaiable at XXX

  </help>
  <citations>
  </citations>
</tool>