Mercurial > repos > iuc > gemini_gene_wise

<tool id="gemini_@BINARY@" name="GEMINI @BINARY@" version="@VERSION@+galaxy1">
    <description>Discover per-gene variant patterns across families</description>
    <expand macro="bio_tools"/>
    <macros>
        <import>gemini_macros.xml</import>
        <token name="@BINARY@">gene_wise</token>
    </macros>
    <expand macro="requirements" />
    <expand macro="stdio" />
    <expand macro="version_command" />
    <command>
<![CDATA[
        gemini @BINARY@

            #if int($min_filters) > 0:
                --min-filters $min_filters
            #end if

            #for $filter in $filter_by_genotype:
                #set $multiline_sql_expr = str($filter.gt_filter)
                #if $filter.is_required:
                    #set $cmdln_param = "--gt-filter-required"
                #else:
                    #set $cmdln_param = "--gt-filter"
                #end if
                @MULTILN_SQL_EXPR_TO_CMDLN@
            #end for

            #set $report = $oformat.report
            @COLUMN_SELECT@

            #set $where_clause_elements = []
            #set $filter_cmdln_param = '--filter'
            #for $cond in $constraint:
                #if str($cond.filter).strip():
                    #silent $where_clause_elements.append(str($cond.filter).strip())
                    #if $cond.overwrite_default_filter:
                        #set $filter_cmdln_param = '--where'
                    #end if
                #end if
            #end for

            @PARSE_REGION_ELEMENTS@
            #if $region_elements:
                #silent $where_clause_elements.append(" OR ".join($region_elements))
            #end if
            #set $filter = " AND ".join($where_clause_elements)
            #if str($filter):
                $filter_cmdln_param '$filter'
            #end if

            '$infile'
            > '$outfile'
]]>
    </command>
    <inputs>
        <expand macro="infile" />
        <expand macro="gt_filter" default_repeat="1" min_repeat="1" max_repeat="999">
            <param name="is_required" type="boolean" checked="False"
            label="Make this an obligate filter that a variant has to pass to be considered"
            help="By default, a variant has to pass a minimum number of genotype filters (set below) to get reported. By making a filter required, you ensure that variants that fail this one filter are always excluded. Required filters that a variant passes do not count towards its number of passed (regular) filters" />
        </expand>
        <param name="min_filters" type="integer" value="1" min="1" label="Minimum number of filters" help="(--min-filters)" />
        <expand macro="region_filter" />
        <expand macro="insert_constraint">
            <expand macro="overwritable_where_default" default_where="exonic, high impact variants (SQL clause: is_exonic = 1 and impact_severity != 'LOW')" />
        </expand>
        <section name="oformat" title="Output - included information" expanded="true">
            <expand macro="column_filter" />
        </section>
    </inputs>
    <outputs>
        <data name="outfile" format="tabular" />
    </outputs>
    <tests>
        <test>
            <param name="infile" value="gemini_amend_input.db" ftype="gemini.sqlite" />
            <repeat name="filter_by_genotype">
                <param name="gt_filter" value="((gt_depths).(*).(>=1).(all))" />
            </repeat>
            <output name="outfile">
                <assert_contents>
                    <has_line_matching expression="variant_id&#009;gene.*" />
                </assert_contents>
            </output>
        </test>
    </tests>
    <help>
<![CDATA[
**What it does**

This tool extends the *GEMINI inheritance pattern* tool in that it lets you
search for custom gene-wise inheritance patterns of variants, instead of fixed
ones.

See also: the `command line tool documentation
<https://gemini.readthedocs.io/en/latest/content/tools.html#gene-wise-custom-genotype-filtering-by-gene>`__

-----

*Genotype filters*

The syntax for specifying a genotype filter (``--gt-filter`` command line
option) is the same as for the *GEMINI query* tool and is described `here
<https://gemini.readthedocs.io/en/latest/content/querying.html#gt-filter-filtering-on-genotypes>`__.

The difference with the *gene_wise* tool is that it lets you specify multiple
such filters and, if you do, every filter can be met by a **different variant**
as long as all of them are in the **same gene**.

This is useful if your analysis includes several families that you suspect
(based on a shared phenotype) to have the same gene affected, but not
necessarily through the same variant. In this case, you can formulate one filter
per family like, for example::

  gt_types.fam1_kid == HET and gt_types.fam1_mom == HOM_REF and gt_types.fam1_dad == HOM_REF

  gt_types.fam2_kid == HET

  gt_types.fam3_kid == HET

, which would allow you to find a causal gene that's affected by different
(dominant) variants in children from three different families. Note that the
first filter combines three conditions applied to family 1, which, thus, must
be met by the same variant site.

*Regular and required filters* (``--gt-filter`` *vs* ``--gt-filter-required``)
and the *Minimum number of filters*

For every single genotype filter you define you can specify whether it should
be applied as a regular or as a required filter. The difference is that, if a
variant doesn't pass a required filter it is excluded from further analysis.
Of the regular filters, a gene and its variants only have to pass a threshold
number defined by *Minimum number of filters* (``--min-filters``). Imagine,
with the above filters you had specified ``--min-filters`` as ``2``, then a
gene for which the child in family 3 carries one copy of a variant allele and
the child in family 3 carries a copy of a different allele would be reported
no matter if any other allele in that gene passes the first filter, *etc.*.

-----

*Region filters*

They let you restrict your analysis to parts of the genome, which can be useful
if you have prior knowledge of the approximate location of the causative gene.

If you specify more then one region filter, they get combined with a logical
*OR*, meaning variants and genes falling in *any* of the regions are reported.

-----

*Additional constraints on variants*

These get translated directly into the WHERE clause of an SQL query and, thus,
have to be expressed in valid SQL syntax. Of particular interest, here, is the
fact that, by default, the *gene-wise* tool applies the WHERE clause:
``is_exonic = 1 and impact_severity != 'LOW'``, which means the tool only
considers variants in exons that are not of *LOW* impact severity (*i.e.*, not
silent mutations). While this can be a good and biologically justifiable
setting, you can overwrite it if you need.

Note that in SQL syntax tests for equality use a single ``=``, while genotype
filters (discussed above) are following Python syntax and use ``==`` for the
same purpose. Also note that non-numerical values need to be enclosed in
single-quotes, *e.g.* ``'LOW'``, but numerical values must *NOT* be.

]]>
    </help>
    <expand macro="citations"/>
</tool>
author	iuc
date	Wed, 13 Jul 2022 15:30:49 +0000
parents	4b26f6c99227
children