NAME
    Annovar::Wrapper - A wrapper around the annovar annotation pipeline

VERSION
    Version 0.06

SYNOPSIS
        annovar-wrapper.pl --vcfs file1.vcf,file2.vcf --annovardb_path /path/to/annovar/dbs

    This module is a wrapper around the popular annotation tool, annovar.
    http://www.openbioinformatics.org/annovar/ . The commands generated are
    taken straight from the documentation. In addition, there is an option
    to reannotate using vcf-annotate from vcftools.

    It takes as its input a list or directory of vcf files, bgzipped and
    tabixed or not, and uses annovar to create annotation files. These
    multianno table files can be optionally reannotated into the vcf file.
    This script does not actually execute any commands, only writes them to
    STDOUT for the user to run as they wish.

    It comes with an executable script annovar-wrapper.pl. This should be
    sufficient for most of your needs, but if you wish to overwrite methods
    you can always do so in the usual Moose fashion.

        #!/usr/bin/env perl 

        package Main;

        use Moose;
        extends 'Annovar::Wrapper';

        Annovar::Wrapper->new_with_options->run;

        sub method_to_override {
            my $self = shift;

            #dostuff
        };

        before 'method' => sub  {
            my $self = shift;

            #dostuff
        };

        has '+variable' => (
            #things to add to variable declaration
        );

        #or 
    
        has 'variable' => (
            #override variable declaration
        );

        1;

    Please see the Moose::Manual::MethodModifiers for more information.

Prerequisites
    This module requires the annovar download. The easiest thing to do is to
    put the annovar scripts in your ENV{PATH}, but if you choose not to do
    this you can also pass in the location with

    annovar-wrapper.pl --tableannovar_path /path/to/table_annovar.pl
    --convert2annovar_path /path/to/convert2annovar.pl

    It requires Vcf.pm, which comes with vcftools.

    Vcftools is publicly available for download.
    http://vcftools.sourceforge.net/.

        export PERL5LIB=$PERL5LIB:path_to_vcftools/perl

    If you wish to you reannotate the vcf file you need to have bgzip and
    tabix installed, and have the executables in vcftools in your path.

        export PATH=$PATH:path_to_vcftools

Generate an Example
    To generate an example you can run the following commands

        tabix -h ftp://ftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20100804/ALL.2of4intersection.20100804.genotypes.vcf.gz 2:39967768-40000000 > test.vcf
        bgzip test.vcf
        tabix test.vcf.gz
        vcf-subset -c HG00098,HG00100,HG00106,HG00112,HG00114 test.vcf.gz | bgzip -c > out.vcf.gz
        tabix out.vcf.gz
        rm test.vcf.gz
        rm test.vcf.gz.tbi

        annovar-wrapper.pl --vcfs out.vcf.gz --annovar_dbs refGene --annovar_fun g --outdir annovar_out --annovardb_path /path/to/annovar/dbs > my_cmds.sh

    There is more detail on the example in the pod files.

Variables
  Annovar Options
   tableannovar_path
    You can put the location of the annovar scripts in your ENV{PATH}, and
    the default is fine. If annovar is not in your PATH, please supply the
    location.

   convert2annovar_path
    You can put the location of the annovar scripts in your ENV{PATH}, and
    the default is fine. If annovar is not in your PATH, please supply the
    location

   annovardb_path
    Path to your annovar databases

   buildver
    Its probably hg19 or hg18

   convert2annovar_opts
    Assumes vcf version 4 and that you want to convert all samples

    Not using --allsample on a multisample vcf is untested and will probably
    break the whole pipeline

   annovar_dbs
    These are pretty much all the databases listed on

    http://www.openbioinformatics.org/annovar/annovar_download.html for hg19
    that I tested as working

        #Download databases with

        cd path_to_annovar_dir
        ./annotate_variation.pl --buildver hg19 -downdb -webfrom annovar esp6500si_aa hg19/

        #Option is an ArrayRef, and can be given as either

        --annovar_dbs cg46,cg69,nci60

        #or

        --annovar_dbs cg46 --annovar_dbs cg69 --annovar_dbs nci60

   annovar_fun
    Functions of the individual databases can be found at

    What function your DB may already be listed otherwise it is probably
    listed in the URLS under Annotation: Gene-Based, Region-Based, or
    Filter-Based

    Functions must be given in the corresponding order of your annovar_dbs

        #Option is an ArrayRef, and can be given as either

        --anovar_fun f,f,g

        #or 

        --annovar_fun f --annovar_fun f --annovar_fun g

   annovar_cols
    Some database annotations generate multiple columns. For reannotating
    the vcf we need to know what these columns are. Below are the columns
    generated for the databases given in annovar_dbs

    To add give a hashref of array

  Wrapper Options
   indir
    A path to your vcf files can be given, and using File::Find::Rule it
    will recursively search for vcf or vcf.gz

   vcfs
    VCF files can be given individually as well.

        #Option is an ArrayRef and can be given as either 

        --vcfs 1.vcf,2.vcf,3.vcfs

        #or

        --vcfs 1.vcf --vcfs 2.vcf --vcfs 3.vcf

    Don't mix the methods

   outdir
    Path to write out annotation files. It creates the structure

        outdir
            --annovar_interim
            --annovar_final
            --vcf-annotate_interim #If you choose to reannotate VCF file
            --vcf-annotate_final #If you choose to reannotate VCF file

    A lot of interim files are created by annovar, and the only one that
    really matters unless you debugging a new database is the multianno file
    found in annovar_final

    If not given the outdirectory is assumed to be the current working
    directory.

   annotate_vcf
    Use vcf-annotate from VCF tools to annotate the VCF file

    This does not overwrite the original VCF file, but instead creates a new
    one

    To turn this off

        annovar-wrapper.pl --annotate_vcf 0

SUBROUTINES/METHODS
  run
    Subroutine that starts everything off

  print_opts
    Print out the command line options

  check_files
    Check to make sure either an indir or vcfs are supplied

  find_vcfs
    Use File::Find::Rule to find the vcfs

  parse_commands
    Allow for giving ArrayRef either in the usual fashion or with commas

  write_annovar
    Write the commands that

    Convert the vcf file to annovar input Do the annotations Reannotate the
    vcf - if you want

  get_samples
    Using VCF tools get the samples listed per vcf file

    Supports files that are bgzipped or not

    Sample names are stripped of all non alphanumeric characters.

  convert_annovar
    Print out the command to print the convert2annovar commands

  table_annovar
    Print out the commands to generate the annotation using table_annovar.pl
    command.

  vcf_annotate
    Generate the commands to annotate the vcf file using vcf-annotate

  gen_descr
    Bgzip, tabix, all of vcftools, and sort must be in your PATH for these
    to work.

    There are two parts to this command.

    The first prepares the annotation file.

    1. The annotation file is backed up just in case 2. The annotation file
    is sorted, because I had some problems with sorting 3. The annotation
    file is bgzipped, as required by vcf-annotate 4. The annotation file is
    tabix indexed using the special commands -s 1 -b 2 -e 3

    The second writes out the vcf-annotate commands

    Example with RefGene zcat ../../variants.vcf.gz | vcf-annotate -a
    sorted.annotation.gz \ -d
    key=INFO,ID=SAMPLEID_Func_refGene,Number=0,Type=String,Description='SAMP
    LEID Annovar Func_refGene' \ -d
    key=INFO,ID=SAMPLEID_Gene_refGene,Number=0,Type=String,Description='SAMP
    LEID Annovar Gene_refGene' \ -d
    key=INFO,ID=SAMPLEID_ExonicFun_refGene,Number=0,Type=String,Description=
    'SAMPLEID Annovar ExonicFun_refGene' \ -d
    key=INFO,ID=SAMPLEID_AAChange_refGene,Number=0,Type=String,Description='
    SAMPLEID Annovar AAChange_refGene' \ -c
    CHROM,FROM,TO,-,-,INFO/SAMPLEID_Func_refGene,INFO/SAMPLEID_Gene_refGene,
    INFO/SAMPLEID_ExonicFun_refGene,INFO/SAMPLEID_AAChange_refGene >
    SAMPLEID.annotated.vcf

  gen_cols
    Generate the -c portion of the vcf-annotate command

  merge_vcfs
    There is one vcf-annotated file per sample, so merge those at the the
    end to get a multisample file using vcf-merge

  subset_vcfs
    vcf-merge used in this fashion will create a lot of redundant columns,
    because it wants to assume all sample names are unique

    Straight from the vcftools documentation

    vcf-subset -c NA0001,NA0002 file.vcf.gz | bgzip -c > out.vcf.gz

AUTHOR
    Jillian Rowe, "<jillian.e.rowe at gmail.com>"

BUGS
    Please report any bugs or feature requests to "bug-annovar-wrapper at
    rt.cpan.org", or through the web interface at
    <http://rt.cpan.org/NoAuth/ReportBug.html?Queue=Annovar-Wrapper>. I will
    be notified, and then you'll automatically be notified of progress on
    your bug as I make changes.

SUPPORT
    You can find documentation for this module with the perldoc command.

        perldoc Annovar::Wrapper

    You can also look for information at:

    *   RT: CPAN's request tracker (report bugs here)

        <http://rt.cpan.org/NoAuth/Bugs.html?Dist=Annovar-Wrapper>

    *   AnnoCPAN: Annotated CPAN documentation

        <http://annocpan.org/dist/Annovar-Wrapper>

    *   CPAN Ratings

        <http://cpanratings.perl.org/d/Annovar-Wrapper>

    *   Search CPAN

        <http://search.cpan.org/dist/Annovar-Wrapper/>

ACKNOWLEDGEMENTS
    This module is a wrapper around the well developed annovar pipeline. The
    commands come straight from the documentation.

    This module was originally developed at and for Weill Cornell Medical
    College in Qatar within ITS Advanced Computing Team and input by Khalid
    Fahkro. With approval from WCMC-Q, this information was generalized and
    put on github, for which the authors would like to express their
    gratitude.

LICENSE AND COPYRIGHT
    Copyright 2014 Jillian Rowe.

    This program is free software; you can redistribute it and/or modify it
    under the terms of the the Artistic License (2.0). You may obtain a copy
    of the full license at:

    <http://www.perlfoundation.org/artistic_license_2_0>

    Any use, modification, and distribution of the Standard or Modified
    Versions is governed by this Artistic License. By using, modifying or
    distributing the Package, you accept this license. Do not use, modify,
    or distribute the Package, if you do not accept this license.

    If your Modified Version has been derived from a Modified Version made
    by someone other than you, you are nevertheless required to ensure that
    your Modified Version complies with the requirements of this license.

    This license does not grant you the right to use any trademark, service
    mark, tradename, or logo of the Copyright Holder.

    This license includes the non-exclusive, worldwide, free-of-charge
    patent license to make, have made, use, offer to sell, sell, import and
    otherwise transfer the Package with respect to any patent claims
    licensable by the Copyright Holder that are necessarily infringed by the
    Package. If you institute patent litigation (including a cross-claim or
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    direct or contributory patent infringement, then this Artistic License
    to you shall terminate on the date that such litigation is filed.

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