<tool id="genehunter_modscore" name="Genehunter-Modscore" version="@VERSION@.0" >
    <description>Linkage and Haplotypes analysis</description>
    <macros>
        <token name="@VERSION@">3.0.0</token>
        <xml name="macro_npl_opts" >
            <param name="extra_npl_score" type="select" label="Type of NPL scoring">
                <option value="all" selected="true" >All</option>
                <option value="pairs" >Pairs</option>
                <option value="hom" >Homozygous</option>
            </param>
        </xml>
        <!-- Input test file collection -->
        <xml name="test_input_files">
            <param name="inp_ped" value="pedin_1.21" />
            <param name="inp_dat" value="datain_1.21" />
            <param name="inp_map" value="map_1.21" />
        </xml>
        <!-- End Input test file collection -->
        <!-- Output test file(s) -->
        <xml name="test_output_fparam">
            <output name="fparam" >
                <assert_contents>
                    <has_text_matching expression="\s*\d+\.\d+\s+-\d+\.\d+(\s+\d+\.\d+){2}\s+rs17000204$" />
                </assert_contents>
            </output>
        </xml>
        <xml name="test_output_haplo">
            <output name="ihaplo" >
                <assert_contents>
                    <has_text_matching expression="1\s+206006\s+206001\s+206002\s+2\s+2(\s+[0-2])+" />
                </assert_contents>
            </output>
        </xml>
        <!-- End Output test file(s) -->
    </macros>
    <requirements>
        <requirement type="package" version="@VERSION@" >ghm</requirement>
        <requirement type="package" version="2017.3" >linkage2allegro</requirement>
    </requirements>
    <version_command><![CDATA[
    echo q | ghm | grep -oP "(?<=(\(version\ ))[^)]+"
    ]]>
    </version_command>
    <command detect_errors='exit_code'><![CDATA[
ghm < '$setup_file'

&& linkage2allegro
    '${inp_ped}'
    '${inp_map}'
    genehunter
    -l gh.out
#if $section_haplo.analysis_haplo.extra_haplotype
    -h haplo.dump
#end if

&& mv linkage.allegro_lod '${fparam}'
#if $section_haplo.analysis_haplo.extra_haplotype
&& mv linkage.allegro_haplo '${ihaplo}'
#end if
    ]]>
    </command>
    <configfiles>
        <configfile name="setup_file" ><![CDATA[
photo gh.out

ps off

## Initiate mod score lod calculation and store IVs, off by default
modcalc ${section_options.section_pvalues.advanced_options_modcalc.extra_modcalc}
## global / single / off

haplotype ${section_haplo.analysis_haplo.extra_haplotype}
## on / off, generate Haplotypes

#if $section_haplo.analysis_haplo.extra_haplotype
haplotype method ${section_haplo.analysis_haplo.extra_haplotype_method}
## [MaxProb] / Viterbi
#end if

analysis ${section_linkage.npl_scoring.extra_mod_analysis}
## NPL / LOD / BOTH, type of linkage analysis

#if $section_linkage.npl_scoring.extra_mod_analysis.value != 'LOD':
score ${section_linkage.npl_scoring.extra_npl_score}
## pairs / all / hom
#else
score all
#end if

#if $section_linkage.extra_singlepoint
single point ${section_linkage.extra_singlepoint}
## on / off, dont use multi-point parametric
#end if

## -- Re-enable in 3.1
## Algebraic calculation for P-values, default on
## #if $section_options.section_pvalues.advanced_options_alg.extra_alg
## alg ${section_options.section_pvalues.advanced_options_alg.extra_alg}
## Use more memory for algebraic calculations
## algebra ${section_options.section_pvalues.advanced_options_alg.extra_alg_mem}
## #end if

## Add custom trait models
#if $section_options.section_pvalues.advanced_options_model.extra_mod_model
model ${section_options.section_pvalues.advanced_options_model.extra_mod_modeldisfreq} ${section_options.section_pvalues.advanced_options_model.extra_mod_modelpenet}
#end if

## Range of markers positions instead of all range
#if $section_options.section_range.advanced_options_positions.extra_mod_positions
##    #try
##        #assert $section_options.section_range.advanced_options_positions.extra_mod_positions_lowest < $section_options.section_range.advanced_options_positions.extra_mod_positions_highest
##    #except AssertionError
##       #echo Range minimum is not less than the maximum
##    #end try
positions ${section_options.section_range.advanced_options_positions.extra_mod_positions_lowest} ${section_options.section_range.advanced_options_positions.extra_mod_positions_highest}
#end if

## Untyped, default on
#if $section_haplo.analysis_haplo.extra_haplotype or $section_options.section_sample.extra_includeuntyped
include untyped on
#else:
include untyped off
#end if

## Eliminate uninformative individuals, default off
discard ${section_options.section_sample.extra_discard}

## Use untyped founders, default off
ufo ${section_options.section_sample.extra_ufo}

## Restrict penetrances so that hom wildtype LEQ het LEQ hom mutant, on default
pr ${section_options.section_allfreq.extra_mod_penetrancerestrict}

## Restrict disease allele frequency to be not higher than the highest allfreq  (default 0.5)
#if $section_options.section_allfreq.extra_mod_allfreq
ar $section_options.section_allfreq.extra_mod_allfreq
## Set upper disease allele freq for MOD, default 0.5 ( 0 -> 1 )
ha $section_options.section_allfreq.extra_mod_highallele
#end if

## Number of parameters varied together in MOD, default 2 ( 1 -> 5 )
dimensions ${section_options.section_pvalues.extra_mod_dimensions}

## Normalize Allele Frequencies, default off
naf ${section_options.section_allfreq.extra_nmaf}

## off by default
#if '${section_options.section_pvalues.advanced_options_modcalc.extra_modcalc}' == 'single':
## Number of trait models saved in MOD score.
## Only works if algebraic calc is off, and in single modcalc
    #if not('${extra_alg}'):
        #if '${extra_mod_savedmodels}'!=-1:
saved models $extra_mod_savedmodels
        #end if
    #end if

## Long output for modcalc single
$section_options.section_pvalues.extra_mod_longmod

## Calculate P-values only at the best position, off by default
$section_options.section_pvalues.extra_mod_bep
#end if


## Calculate p-values for MOD/LOD scores
#if $section_options.section_pvalues.advanced_options_calcpval.extra_calcpval
cpv $section_options.section_pvalues.advanced_options_calcpval.extra_calcpval_file
## Number of replicates in P-score evaluation, default 0
    #if $section_options.section_pvalues.advanced_options_calcpval.extra_cpv_nor > 0
nor $section_options.section_pvalues.advanced_options_calcpval.extra_cpv_nor
    #end if
#end if

## Number of sequential simulations in P-score evaluation, default 0
seq ${section_options.section_pvalues.extra_seq}

## Store replicates during P-score evaluation, default off
str ${section_options.section_pvalues.extra_storereplicates}  ## pre / both / off (default)

## Simulate untyped individuals, required for haplotypes
#if $section_haplo.analysis_haplo.extra_haplotype or $section_options.section_sample.extra_sun
sun on
#else
sun off
#end if

## Set random seed for P-score evaluation, default -1
srs ${section_options.section_pvalues.extra_srs}

## Display distribution of replicates, default off
sdi ${section_options.section_display.extra_sdi}

#### General
## Count the number of recombintions, default off
count recs ${section_options.section_display.extra_countrec}

## Do not skip fully homozygous markers when generating haplotypes, default off
fin ${section_options.section_sample.extra_cpv_fin}

## Print scores to screen, default on
display scores on

## Margin before and after marker range to compute scores, default 0 cM
off end ${section_options.section_range.extra_offend}

## Distance between adjacent scores, either in cM 'distance' irrespective of
## map, or equal 'steps'. Default steps 2
increment ${section_options.section_range.advanced_options_increment.extra_increment_type} ${section_options.section_range.advanced_options_increment.extra_increment_sizepavu}

## Units, default haldane
map function ${section_options.section_display.extra_mapfunc}
## Units in scan output, default cM
units ${section_options.section_display.extra_scan_units}

## Max pedigree size  calculated by 2N - F, default 19, trim individuals beyond this
max bits ${section_options.section_range.extra_maxbits}
## Split pedigree larger than max ped size, default off
skip large ${section_options.section_range.extra_maxbits_skiplarge}
## Stores IBD matrics for linkage, default off
cs ${section_options.section_pvalues.extra_computesharing}


load markers ${inp_dat}
read map ${inp_map}
use

scan ${inp_ped}

## Show total scores from a scan of multiple peds
##  - 'het' [alpha], if not given then alpha varies
##  - 'stat'
## default below, overridden by params
total stat het


## TODO:
## Qualitative / Quantitative trait mapping of sibs, Variance component analysis, TDT
q
]]>
        </configfile>
    </configfiles>
    <inputs>
        <param name="inp_ped" type="data" format="linkage_pedin" label="Pedigree" />
        <param name="inp_dat" type="data" format="linkage_datain" label="Recombination Freqs" />
        <param name="inp_map" type="data" format="linkage_map" label="Marker Positions" />

        <section name="section_haplo" title="Haplotypes" expanded="true" >
            <conditional name="analysis_haplo" >
                <param name="extra_haplotype" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Haplotype Analysis" />
                <when value="on">
                    <param name="extra_haplotype_method" type="select" label="Haplotype Reconstruction Algorithm. MaxProb is fastest, and has more global solution." >
                        <option value="MaxProb" selected="true" >Maximisation Probability</option>
                        <option value="Viterbi" >Viterbi</option>
                    </param>
                </when>
                <when value="off" />
            </conditional>
        </section>

        <section name="section_linkage" title="Linkage" expanded="false" >
            <param name="extra_singlepoint" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Single-point Analysis"/>
            <conditional name="npl_scoring" >
                <param name="extra_mod_analysis" type="select" label="Type of linkage analysis" >
                    <option value="BOTH" selected="true" >Both</option>
                    <option value="NPL" >Non-paremetric Linkage</option>
                    <option value="LOD" >Logarithm-of-the-Odds</option>
                </param>
                <when value="BOTH" ><expand macro="macro_npl_opts" /></when>
                <when value="NPL" ><expand macro="macro_npl_opts" /></when>
                <when value="LOD" />
            </conditional>
        </section>

        <section name="section_options" expanded="false" title="Advanced Options" >
            <!-- P-values -->
            <section name="section_pvalues" expanded="false"
                     title="P-value Options" >
                <conditional name="advanced_options_alg" >
                    <param name="extra_alg" type="boolean" truevalue="on" falsevalue="off" checked="true" label="Use Algebraic calculations for P-Values"/>

                    <when value="on" >
                        <param name="extra_alg_mem" type="boolean" truevalue="on" falsevalue="off" checked="true" label="Remove large memory restrictions for algebraic calculations" />
                    </when>
                    <when value="off" >
                        <param name="extra_mod_savedmodels" type="integer" value="-1" label="Number of models to save" />
                    </when>
                </conditional>

                <conditional name="advanced_options_model" >
                    <param name="extra_mod_model" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Use custom trait models" />
                    <when value="on" >
                        <param name="extra_mod_modeldisfreq" type="float" value="" min="0" max="1" label="Disease allele frequency" />
                        <param name="extra_mod_modelpenet" type="text" value="" label="3 or 4 penetrances" />
                    </when>
                    <when value="off" />
                </conditional>

                <conditional name="advanced_options_calcpval" >
                    <param name="extra_calcpval" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Calculate P-values for MOD/LOD scores" />

                    <when value="on" >
                        <param name="extra_calcpval_file" type="data" format="txt" label="Filename to produce values" />
                        <param name="extra_cpv_nor" type="integer" value="0" min="0" label="Number of replicates in P-value calculations" />
                    </when>
                    <when value="off" />
                </conditional>

                <conditional name="advanced_options_modcalc" >
                    <param name="extra_modcalc" type="select" label="Inheritance Vector storage for LOD and P-value calculations" >
                        <option value="global" >Global</option>
                        <option value="single" >Single</option>
                        <option value="off" selected="true" >Off</option>
                    </param>
                    <when value="single" >
                        <param name="extra_mod_longmod" type="boolean" truevalue="lm on" falsevalue="" checked="false" label="Produce long output for scores" />
                        <param name="extra_mod_bep" type="boolean" truevalue="bep on" falsevalue="" checked="false" label="Calculate P-values only at the best LOD positions" />
                    </when>
                    <when value="global" />
                    <when value="off" />
                </conditional>

                <param name="extra_seq" type="integer" value="0" min="0" label="Number of sequential simulations in P-value calculations" />
                <param name="extra_storereplicates" type="select" label="Store replicates during P-value calculations" >
                    <option value="pre" >Pre</option>
                    <option value="both" >Both</option>
                    <option value="off" selected="true" >Off</option>
                </param>
                <param name="extra_srs" type="integer" value="-1" label="Set Random seed for P-value calculations" />
                <param name="extra_computesharing" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Store IBD matrices" />
                <param name="extra_mod_dimensions" type="integer" min="1" max="5" value="2" label="Number of parameters to vary in LOD calculations" />
            </section>
            <!-- End of P Values: Works -->

            <!-- Display Options -->
            <section name="section_display" expanded="false" title="Display options" >
                <param name="extra_sdi" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Display distribution of replicates" />
                <param name="extra_countrec" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Print the number of recombinations" />
                <param name="extra_mapfunc" type="select" label="Genetic map function units" >
                    <option value="haldane" selected="true">Haldane</option>
                    <option value="kosambi" >Kosambi</option>
                </param>
                <param name="extra_scan_units" type="select" label="Output units" >
                    <option value="cM" selected="true">CentiMorgans</option>
                    <option value="rec-frac" >Recombination Fractions</option>
                </param>
            </section>
            <!-- End of display: Works -->

            <!-- Range section -->
            <section name="section_range" expanded="false" title="Range options" >
                <conditional name="advanced_options_positions" >
                    <param name="extra_mod_positions" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Define custom position range" />
                    <when value="off" />
                    <when value="on" >
                        <param name="extra_mod_positions_lowest" type="float" value="0" min="0" max="1000" label="Lowest position (cM)" />
                        <param name="extra_mod_positions_highest" type="float" value="1" min="0" max="1000" label="Highest position (cM)" />
                        <!-- Assert: lowest < higher -->
                    </when>
                </conditional>

                <param name="extra_offend" type="float" value="0.0" label="Margin before and after marker range to compute scores (cM)" />

                <conditional name="advanced_options_increment" >
                    <param name="extra_increment_type" type="select" label="Increment either the genetic distance across the whole range of markers, or the number of equally-spaced steps between adjacent markers" help="Note that the total number of steps (markers * calc. per step)  must not exceed 1000." >
                        <option value="distance" >Distance</option>
                        <option value="steps" selected="true" >Steps</option>
                    </param>
                    <when value="distance" >
                        <param name="extra_increment_sizepavu" type="float" min="1.0" value="1" max="1000" label="centiMorgan interval" />
                    </when>
                    <when value="steps" >
                        <param name="extra_increment_sizepavu" type="integer" min="1" value="2" max="30" label="Number of steps between markers." />
                    </when>
                </conditional>

                <param name="extra_maxbits" type="integer" min="3" value="19" max="30" label="Max bit-size of the pedigree, computed via '2N-F', for F founders and N non-founders" />
                <param name="extra_maxbits_skiplarge" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Split pedigrees if larger than the max pedigree size" />
            </section>
            <!-- End of range:Works -->

            <!-- Frequency section -->
            <section name="section_allfreq" title="Allele Frequency Options">
                <param name="extra_nmaf" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Normalize Allele Frequencies" />

                <param name="extra_mod_allfreq" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Restrict disease allele frequency" />

                <param name="extra_mod_highallele" type="float" min="0" max="1" value="0.5" label="Set maximum disease allele frequency" />

                <param name="extra_mod_penetrancerestrict" type="boolean" truevalue="on" falsevalue="off" checked="true" label="Restrict Penetrances" />

            </section>
            <!-- End of Frequency section:Works -->

            <!-- Sample Individuals section -->
            <section name="section_sample" title="Sample Options" >
                <param name="extra_sun" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Simulate untyped individuals" />
                <param name="extra_includeuntyped" type="boolean" truevalue="on" falsevalue="off" checked="true" label="Include untyped individuals" />
                <param name="extra_cpv_fin" type="boolean" truevalue="on" falsevalue="off" checked="true" label="Process fully homozygous (uninformative) genotypes" />
                <param name="extra_discard" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Discard uninformative individuals"  />
                <param name="extra_ufo" type="boolean" truevalue="on" falsevalue="off" checked="false" label="Use untyped founders" />
            </section>
            <!-- End of sample individuals -->
        </section>
        <!-- End of advanced options -->
    </inputs>

    <outputs>
        <!-- All outputs convert to an Allegro format -->
        <data name="ihaplo" format="allegro_ihaplo" label="${tool.name} on ${on_string}: Haplotypes" />
        <data name="fparam" format="allegro_fparam" label="${tool.name} on ${on_string}: MPT Linkage" />
    </outputs>

    <tests>
        <test><!-- Defaults with haplo -->
            <expand macro="test_input_files" />

            <param name="extra_haplotype" value="on" />

            <expand macro="test_output_fparam" />
            <expand macro="test_output_haplo" />
        </test>
        <test><!-- Haplotypes via Viterbi resolution -->
            <expand macro="test_input_files" />

            <param name="extra_mod_analysis" value="BOTH" />
            <param name="extra_haplotype" value="on" />
            <param name="extra_haplotype_method" value="Viterbi" />
            <param name="extra_increment_sizepavu" value="10" />

            <expand macro="test_output_haplo" />
            <expand macro="test_output_fparam" />
        </test>
        <test><!-- Parametric LOD with restricted scoring -->
            <expand macro="test_input_files" />

            <param name="extra_mod_allfreq" value="on" />
            <param name="extra_mod_highallele" value="0.8" />
            <param name="extra_npl_score" value="hom" />

            <expand macro="test_output_fparam" />
        </test>
        <test><!-- Haplo + Single IBS with computed founders -->
            <expand macro="test_input_files" />

            <param name="extra_cpv_fin" value="on" />
            <param name="extra_modcalc" value="single" />
            <param name="extra_mod_bep" value="bep on" />
            <param name="extra_srs" value="10" />

            <expand macro="test_output_fparam" />
        </test>
    </tests>

    <help><![CDATA[

**Genehunter-MODscore** calculates a *maximized LOD* (MOD) score over a set of genotypes for use in linkage and haplotype analysis.

Haplotypes are generated using either this maximum probability approach, or via slower more conventional Viterbi crawling.

Untyped founders can be simulated by reconstructing their haplotypes from offspring, and points of recombination can still be accurately determined in lieu of this.

Due to the stochastic nature of the analysis, a random seed can be set by the user to produce reproducible results.

Many more configurable options are outlined in the the official manual_.

.. _manual: https://www.helmholtz-muenchen.de/fileadmin/GENEPI/downloads/ghm-3.0.pdf

]]>
    </help>
    <citations>
        <citation type="doi">10.1159/000369065</citation>
        <citation type="doi">10.1002/gepi.20264</citation>
        <citation type="doi">10.1093/bioinformatics/btl539</citation>
        <citation type="doi">10.1186/1471-2156-6-S1-S162</citation>
    </citations>
</tool>