varcontext

Tool for variant effect prediction and transcript generation

Introduction

Varcontext applies SNVs, indels and complex variants to transcript sequences obtained from ensembl and returns the resulting amino acid sequence, along with other variant information.

Germline variants are only taken into account as such, when labeled in the variant_id column by: 'gs[0-9]+'. (e.g. gs123)

Installation instructions

To set up a new MySQL ensembl mirror, do the following:

1. sudo apt-get update
2. sudo apt-get install mysql-server
3. sudo mysql_secure_installation and set up MySQL
4. to mirror the ensembl data, follow the instructions here: Installing the Ensembl Data
   you only need the data in homo_sapiens_core_**_**

For the perl script to run, you also might need the following modules:

1. perl -MCPAN -e 'install DBI'
2. sudo apt-get install libdbd-mysql-perl

Input file definition

Input files should contain at least the following columns (in identical order):

variant_id	chromosome	start_position	ref_allele	alt_allele

Optional columns are:

dna_ref_read_count	dna_alt_read_count	dna_total_read_count	dna_vaf	rna_ref_read_count	rna_alt_read_count	rna_total_read_count	rna_vaf	rna_alt_expression

NOTE: Columns are read in order, from left to right. No header checking is done (i.e. first line is skipped), so column order is VITAL to proper processing of the input file.

Usage example

Varcontext can be called from a wrapper script (availabe in neolution-prep) or directly from the Terminal by:

export ENSEMBLAPI=/path/to/ensembl_api/;perl /path/to/varcontext/create_context.pl --ARGUMENTS INPUT_FILE 1> OUTPUT_FILE 2> LOG_FILE

NOTE: environment variable ENSEMBLAPI must be set to full ensembl API path and include trailing slash ('/')

Optional arguments

• --separator=VALUE - field separator for input file (default = "\t")
• --canonical - only fetch and apply edits to canonical transcripts (default: FALSE)
• --nmd - infer nonsense-mediated decay status (default = FALSE)
• --peptide - report peptide context only (default: FALSE)

Package definitions

• ensembl - a wrapper around the Ensembl API
• EditSeq
• EditTranscript
• Variant - describes a genomic variant using chromosome, start_position, ref_allele and alt_allele
• VariantSet - a set of variants and the ability to assign transcripts and edit them

To do

• VCF input
• NORMAL control samples
• Write tests (e.g. a testset of genes with a couple of designed mutations)