<tool id="gemini_@BINARY@" name="GEMINI @BINARY@" version="@VERSION@.0">
    <description>Find genes among variants that are interacting partners</description>
    <macros>
        <import>gemini_macros.xml</import>
        <token name="@BINARY@">interactions</token>
    </macros>
    <expand macro="requirements" />
    <expand macro="stdio" />
    <expand macro="version_command" />
    <command>
<![CDATA[
        gemini
            #if $annotation_databases:
                --annotation-dir "${annotation_databases.fields.path}"
            #end if

            #if $gene.gene_selector == 'lof':
                ## lof interactions is a separate program
                lof_interactions
            #else:
                ## use normal gemini interactions program
                @BINARY@
                -g "${gene.gene}"
            #end if

            -r "${radius}"
            $variant_mode
            "${ infile }"
            > "${ outfile }"
]]>
    </command>
    <inputs>
        <expand macro="infile" />

        <conditional name="gene">
            <param name="gene_selector" type="select" label="Studying" help="">
                <option value="gene">Interesting gene</option>
                <option value="lof">All loss-of-function variants</option>
            </param>
            <when value="gene">
                <param name="gene" type="text" label="Specify gene name" help="e.g. PTPN22 (-g)" />
            </when>
            <when value="lof"/>
        </conditional>
        <expand macro="annotation_dir" />
        <expand macro="radius" />
        <expand macro="variant_mode" />
    </inputs>
    <outputs>
        <data name="outfile" format="tabular" />
    </outputs>
    <tests>
        <test>
            <param name="infile" value="gemini_burden_input.db" ftype="gemini.sqlite" />
            <param name="gene" value="CTBP2" />
            <param name="radius" value="5" />
            <output name="outfile" file="gemini_interactions_result.tabular" />
        </test>
    </tests>
    <help><![CDATA[
**What it does**

Integrating the knowledge of the known protein-protein interactions would be useful in explaining variation data.
Meaning to say that a damaging variant in an interacting partner of a potential protein may be equally interesting as the
protein itself. We have used the HPRD_ binary interaction data to build a p-p network graph which can be explored by GEMINI.

.. _HPRD: http://www.ncbi.nlm.nih.gov/pubmed/18988627

**Details**

*interactions: Find genes among variants that are interacting partners.*

Integrating the knowledge of the known protein-protein interactions would be useful in explaining variation data. Meaning to say that a damaging variant in an interacting partner of a potential protein may be equally interesting as the protein itself. We have used the HPRD binary interaction data to build a p-p network graph which can be explored by GEMINI.

**Examples**

EXAMPLE with setting -g CTBP2 and -r 3::

 sample   gene    order_of_interaction    interacting_gene
 M128215  CTBP2   0_order:                CTBP2
 M128215  CTBP2   1_order:                RAI2
 M128215  CTBP2   2_order:                RB1
 M128215  CTBP2   3_order:                TGM2,NOTCH2NL

Return CTBP2 (-g) interacting gene variants till the third order (-r)

EXAMPLE lof_interactions (use this option to restrict your analysis to only LoF variants); lof_interactions and -r 3::

 sample    lof_gene    order_of_interaction    interacting_gene
 M128215   TGM2        1_order:                RB1
 M128215   TGM2        2_order:                none
 M128215   TGM2        3_order:                NOTCH2NL,CTBP2

Meaning to say return all LoF gene TGM2 (in sample M128215) interacting partners to a 3rd order of interaction.

EXAMPLE --var. An extended variant information (chrom, start, end etc.) for the interacting gene may be achieved with the –var option for both the interactions and the lof_interactions. Settings '-g CTBP2', '-r 3' and '--var'::

 sample   gene    order_of_interaction    interacting_gene    var_id  chrom   start           end             impact          biotype         in_dbsnp    clinvar_sig   clinvar_disease_name    aaf_1kg_all     aaf_esp_all
 M128215  CTBP2   0                       CTBP2               5       chr10   126678091       126678092       stop_gain       protein_coding  1           None          None                    None            None
 M128215  CTBP2   1                       RAI2                9       chrX    17819376        17819377        non_syn_coding  protein_coding  1           None          None                    1               0.000473
 M128215  CTBP2   2                       RB1                 7       chr13   48873834        48873835        upstream        protein_coding  1           None          None                    0.94            None
 M128215  CTBP2   3                       NOTCH2NL            1       chr1    145273344       145273345       non_syn_coding  protein_coding  1           None          None                    None            None
 M128215  CTBP2   3                       TGM2                8       chr20   36779423        36779424        stop_gain       protein_coding  0           None          None                    None            None

EXAMPLE with the following settings; '-r 3', '--var'::

 sample    lof_gene   order_of_interaction   interacting_gene   var_id   chrom   start         end             impact          biotype         in_dbsnp   clinvar_sig   clinvar_disease_name    aaf_1kg_all     aaf_esp_all
 M128215   TGM2       1                      RB1                7        chr13   48873834      48873835        upstream        protein_coding  1          None          None                    0.94            None
 M128215   TGM2       3                      NOTCH2NL           1        chr1    145273344     145273345       non_syn_coding  protein_coding  1          None          None                    None            None
 M128215   TGM2       3                      CTBP2              5        chr10   126678091     126678092       stop_gain       protein_coding  1          None          None                    None            None

    ]]></help>
    <expand macro="citations">
        <citation type="doi">10.1093/nar/gkn892</citation><!-- HPRD citation -->
    </expand>
</tool>