Variation Model Collaboration Command Line tool.

Version: 1.1.3

Lightweight command line implementation of the VMC SHA-512 algorithm to allow rapid digest generation.

The follow input types are currently allowed:

• Fasta
• VCF
• HGVS

Please keep in mind this tool only implements specific aspects of the entire VMC model. A VMC Bundle and JSON file are not generated or validated.

Usage

Usage: vmccl [--fasta FASTA] [--vcf VCF] [--hgvs HGVS] [--logfile LOGFILE] [--length LENGTH]

Options:
  --fasta FASTA          Will return VMC Sequence digest ID of this fasta file.
  --vcf VCF              Will take input VCF file and updated to include VMC (sequence|location|allele) digest IDs.
  --hgvs HGVS            Valid HGVS expression to digest into VMC record. Double quotes are required.
  --logfile LOGFILE      Filename for output log file. [default: VMCCL.log]
  --length LENGTH        Length of digest id to return. MAX: 64 [default: 24]
  --help, -h             display this help and exit

Installing

Easiest method to run vmccl is to download the most recent executable corresponding to your computer environment.

• Download

OS	Platform	Release
darwin	amd64	darwin
linux	amd64	linux

• Then run (example)

 $> wget <release link> .
 $> mv vmccl_linux64 vmccl
 $> chmod a+x vmccl

Additional builds and features can be requested here

Description

Please review the example section for best practices instructions on how to run vmccl.

Fasta:

vmccl will run the VMC digest algorithm on each record in the fasta file. It will store the results into a file of the same name, with a .vmc extension added. Subsequent runs of vmccl will check for the presence of the fasta.vmc file in the same location as the original fasta file.

The following is the format of the fasta.vmc file:

Leading Identifier (space separated)	VMC Seq ID	Description line of fasta
1	VMC:GS_jqi61wB_nLCsUMtCXsS0Yau_pKxuS21U	1 dna:chromosome chromosome:GRCh37:1:1:249250621:1

• The importance of using the correct fasta files to generate VMC_GS cannot be stressed enough as even a change of a single base will generate a completely different sequence identifier. This is especially important when considering sharing VMC_GA with other institutions.

VCF:

Please review the example section for best practices instructions on how to run vmccl.

At this time to update a VCF file, an accompanying fasta file with a identical Leading Identifier is required. If a fasta.vmc file has already been generated vmccl will look for it in the same location as the original fasta and collect the VMC_GS identifiers.

Note:

• Only VCFs which have ran vt decompose will be accepted.
• If your VCF file contains sequence identifiers not found in the fasta file, the VCF record is printed to the new file without updated annotations.
• If your fasta file contains records not found in the VCF file they are skipped.
• Uses and implementation of the fasta.vmc file will change as the seqrepo becomes more widely available, and/when vmccl implements a SQL database backend.

An example of annotations added to the VCF file:

Added to the VCF header:
##INFO=<ID=VMCGAID,Number=1,Type=String,Description="VMC Allele identifier">
##INFO=<ID=VMCGLID,Number=1,Type=String,Description="VMC Location identifier">
##INFO=<ID=VMCGSID,Number=1,Type=String,Description="VMC Sequence identifier">

Added annotations to the VCF INFO field:
1       949523  183381  C       T       .       .       ALLELEID=181485;CLNDISDB=MedGen:C4015293,OMIM:616126,Orphanet:ORPHA319563;CLNDN=Immunodeficiency_38_with_basal_ganglia_calcification;CLNHGVS=NC_000001.10:g.949523C>T;CLNREVSTAT=no_assertion_criteria_provided;CLNSIG=Pathogenic;CLNVC=single_nucleotide_variant;CLNVCSO=SO:0001483;CLNVI=OMIM_Allelic_Variant:147571.0003;GENEINFO=ISG15:9636;MC=SO:0001587|nonsense;ORIGIN=1;RS=786201005;VMCGSID=VMC:GS_jqi61wB_nLCsUMtCXsS0Yau_pKxuS21U;VMCGLID=VMC:GL_VMC:GS_UqMzt_PvRNhrFl31m8N7SbCGdDpmAtsp;VMCGAID=VMC:GA_VMC:GS_-sajfzQq1Q_PfOAPMPQRodzFclkX8ksp

HGVS:

Currently vmccl will only digest simple HGVS substitutions using the genomic (g) prefix. Future release will begin to include a more dynamic range of HGVS types. Please refer to to examples section to see the standard HGVS run.

Examples

VCF

The best practice method for adding VMC digest IDs to a VCF file are as follows:

1. First create a fasta.vmc file that will be used for all/future VCF updates.

   $> ./vmccl --fasta human_g1k_v37_decoy.fasta
   
   $> ls -l *fasta*
   human_g1k_v37_decoy.fasta 
   human_g1k_v37_decoy.fasta.vmc
   

   • In general creating the fasta.vmc file will take longer then adding annotations to a VCF file, so pre-building it will decrease future VCF runtimes.
   • Please keep in mind the .fasta and .fasta.vmc file will need to be in the same location, or vmccl will rebuild the .fasta.vmc file.

2. Run vmccl on your vcf file.

$> ./vmccl --fasta human_g1k_v37_decoy.fasta --vcf clinvar_20180701.vcf.gz

$> ls -l *fasta* *vcf*
human_g1k_v37_decoy.fasta 
human_g1k_v37_decoy.fasta.vmc

clinvar_20180701.vcf.gz
clinvar_20180701.vmc.vcf.gz

• Output VCFs files will always be gzip compressed.

HGVS

As with VCF files, currently a matching fasta file is required. Once ran vmccl will return the corresponding VMC_GA id.

Ensure double quotes are used.

$> ./vmccl --hgvs "NC_000019.10:g.44908684C>T" --fasta data/NC_000019.10.fasta
$> VMC:GA_AnJl99FJB5tNPupduz8I4R8CCuwCpIY0

TODO

Currency fasta generation utilizes parallel process. Future releases will incorporate parallel process for VCF updating.

BUGS AND LIMITATIONS

Please report any bugs or feature requests to the issue tracker

AUTHOR Shawn Rynearson [email protected]

LICENCE AND COPYRIGHT Copyright (c) 2018, Shawn Rynearson [email protected] All rights reserved.

This module is free software; you can redistribute it and/or modify it under the same terms as GO itself.

DISCLAIMER OF WARRANTY BECAUSE THIS SOFTWARE IS LICENSED FREE OF CHARGE, THERE IS NO WARRANTY FOR THE SOFTWARE, TO THE EXTENT PERMITTED BY APPLICABLE LAW. EXCEPT WHEN OTHERWISE STATED IN WRITING THE COPYRIGHT HOLDERS AND/OR OTHER PARTIES PROVIDE THE SOFTWARE "AS IS" WITHOUT WARRANTY OF ANY KIND, EITHER EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE. THE ENTIRE RISK AS TO THE QUALITY AND PERFORMANCE OF THE SOFTWARE IS WITH YOU. SHOULD THE SOFTWARE PROVE DEFECTIVE, YOU ASSUME THE COST OF ALL NECESSARY SERVICING, REPAIR, OR CORRECTION.

IN NO EVENT UNLESS REQUIRED BY APPLICABLE LAW OR AGREED TO IN WRITING WILL ANY COPYRIGHT HOLDER, OR ANY OTHER PARTY WHO MAY MODIFY AND/OR REDISTRIBUTE THE SOFTWARE AS PERMITTED BY THE ABOVE LICENCE, BE LIABLE TO YOU FOR DAMAGES, INCLUDING ANY GENERAL, SPECIAL, INCIDENTAL, OR CONSEQUENTIAL DAMAGES ARISING OUT OF THE USE OR INABILITY TO USE THE SOFTWARE (INCLUDING BUT NOT LIMITED TO LOSS OF DATA OR DATA BEING RENDERED INACCURATE OR LOSSES SUSTAINED BY YOU OR THIRD PARTIES OR A FAILURE OF THE SOFTWARE TO OPERATE WITH ANY OTHER SOFTWARE), EVEN IF SUCH HOLDER OR OTHER PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES.)))