To address potential installation challenges with VEP dependencies on newer systems, we recommend using Docker or Singularity containers.
These containerised environments enable to access all the latest VEP features without the hassle of installing dependencies directly on your system. Additionally, they are highly compatible with computer clusters.
DownloadDownload ensembl-vep package (see below the different ways to download it) and then follow the installation instructions.
Use git to download the ensembl-vep package:
git clone https://github.com/Ensembl/ensembl-vep.git cd ensembl-vep
To update from a previous version:
cd ensembl-vep git pull git checkout release/114 perl INSTALL.pl
To use an older version (this example shows how to set up release 87):
cd ensembl-vep git checkout release/87 perl INSTALL.pl
Users without the git utility installed may download a zip file from GitHub, though we would always recommend using git if possible.
curl -L -O https://github.com/Ensembl/ensembl-vep/archive/release/114.zip unzip 114.zip cd ensembl-vep-release-114/
Previously VEP was available as part of the ensembl-tools package (see the Ensembl archive site for documentation). The following downloads are available for archival purposes. Show versions
What's new?vep (formerly variant_effect_predictor.pl or vep.pl)VEP requires:
VEP's INSTALL.pl script will install required components of Ensembl API for you, but VEP may also be used with any pre-existing API installations you have, provided their versions match the version of VEP you are using.
VEP is available in the following platforms:
VEP is also available as Docker and Singularity images, allowing to skip the complex installation steps.
InstallationVEP's INSTALL.pl makes it easy to set up your environment for using the VEP. It will download and configure a minimal set of the Ensembl API for use by the VEP, and can also download cache files, FASTA files and plugins.
Run the following, and follow any prompts as they appear:
perl INSTALL.pl
Additional non-essential components and enhancements must be installed manually.
If you already have the latest version of the API installed you do not need to run the installer, although it can be used to simply update your API version (with post-release patches applied), and retrieve cache and FASTA files. The installer downloads the API within the VEP directory and will not affect any other Ensembl API installations.
The script will also attempt to install a Perl::XS module, Bio::DB::HTS, for rapid access to bgzipped FASTA files. If this fails, you may add the --NO_HTSLIB flag when running the installer; VEP will fall back to using Bio::DB::Fasta for this functionality (more details).
The installer is run on the command line as follows:
perl INSTALL.pl [options]
Follow on-screen prompts and note warnings of any files which will be deleted/overwritten
You should not need to add any options, but configuration of the installer is possible with the flags below. Options can also be set by exporting environment variables prefixed with VEP_ before running the installer (for instance, export VEP_NO_HTSLIB=1 and export VEP_DIR_PLUGINS="/plugins").
Flag Alternate Description--ASSEMBLY
-yAssembly version to use when using
--AUTO. Most species have only one assembly available on each software release; currently this is only required for human on release 76 onwards.
--AUTO
-aRun installer without prompts. Use the following options to specify parts to install:
e.g. for API and cache:
perl INSTALL.pl --AUTO ac
--CACHE_VERSION [version]By default the installer will download the latest version of VEP caches and FASTA files (currently 114). You can force the script to install a different version, but there is no guarantee that a version of the API will be compatible with a different version of the cache.
--CACHEDIR [dir]
-c
By default the script will install the cache files in the ".vep" subdirectory in your home area. This option configures where cache files are installed.
The --dir_cache flag must be passed when running the VEP if a non-default cache directory is given:
./vep --dir_cache [dir]
--DESTDIR [dir]
-d
By default the script will install the API modules in a subdirectory of the current directory named "Bio". Using this option you can configure where the Bio directory is created. If something other than the default is used, this directory must either be added to your PERL5LIB environment variable when running the VEP, or included using perl's -I flag:
perl -I [dir] vep
--NO_HTSLIB
-lDon't attempt to install Bio::DB::HTS/htslib
--NO_TESTDon't run API tests - useful if you know a harmless failure will prevent continuation of the installer
--NO_UPDATE
-nBy default the script will check for new versions or updates of the VEP. Using this option will skip this check.
--PLUGINS
-g
Comma-separated list of plugins to install when using --AUTO. To install all available plugins, use --PLUGINS all.
# List the available plugins: perl INSTALL.pl -a p --PLUGINS list # Download/install all the available plugins: perl INSTALL.pl -a p --PLUGINS all # Download/install a defined list of plugins, e.g.: perl INSTALL.pl -a p --PLUGINS dbNSFP,CADD,G2P
--PLUGINSDIR [dir]
-r
By default the script will install the plugins files in the "Plugins" subdirectory of the --CACHEDIR directory. This option configures where the plugins files are installed.
The --dir_plugins flag must be passed when running the VEP if a non-default plugins directory is given:
./vep --dir_plugins [dir]
--PREFER_BIN
-pUse this if the installer fails with "out of memory" errors.
--SPECIES
-s
Comma-separated list of species to install when using --AUTO. To install the RefSeq cache, add "_refseq" to the species name, e.g. "homo_sapiens_refseq", or "_merged" to install the merged Ensembl/RefSeq cache. Remember to use --refseq or --merged when running the VEP with the relevant cache!
Use all to install data for all available species.
--USE_HTTPS_PROTODownload cache and FASTA file using HTTPs protocol instead of FTP. Useful for networks where FTP port is blocked by firewall.
--GITHUBTOKENSet token to use for authentication when querying GitHub API. Authenticated user have increased rate-limit. NOTE: use token with read-only access.
--QUIET
-qDon't write any status output when using
--AUTO. Additional components
INSTALL.pl will set up the minimum requirements for VEP. Some features and enhancements, however, require the installation of additional components. Most are perl modules that are easily installed using cpanm; see this guide for more information on how to install perl modules.
Typically, you will use cpanm to install modules locally in your home directories; this shows how to set up a path for perl modules and install one there:
mkdir -p $HOME/cpanm export PERL5LIB=$PERL5LIB:$HOME/cpanm/lib/perl5 cpanm -l $HOME/cpanm Set::IntervalTree
To make the change to PERL5LIB permanent, it is recommended to add the export line to your $HOME/.bashrc or $HOME/.profile.
In order for VEP to be able to access bigWig format custom annotation files, the Bio::DB::BigFile perl module is required. Installation involves downloading and compiling the kent source tree. The current version of the kent source tree does not work correctly with Bio::DB::BigFile, so it is necessary to install an archive version known to work (v335).
Download and unpack the kent source tree
wget https://github.com/ucscGenomeBrowser/kent/archive/v335_base.tar.gz tar xzf v335_base.tar.gz
Set up some environment variables; these are required only temporarily for this installation process
export KENT_SRC=$PWD/kent-335_base/src export MACHTYPE=$(uname -m) export CFLAGS="-fPIC" export MYSQLINC=`mysql_config --include | sed -e 's/^-I//g'` export MYSQLLIBS=`mysql_config --libs`
Modify kent build parameters
cd $KENT_SRC/lib echo 'CFLAGS="-fPIC"' > ../inc/localEnvironment.mk
Build kent source
make clean && make cd ../jkOwnLib make clean && make
If either of these steps fail, you may have some missing dependencies. Known common missing dependencies are libpng and libssl; these may be installed, for example, with apt-get on Ubuntu. If you do not have sudo access you may have to ask your sysadmin to install any missing dependencies.
sudo apt-get install libpng-dev libssl-dev
On macOS you may use brew; the openssl libraries also need to be symbolically linked to a different path:
brew install libpng openssl cd /usr/local/include ln -s ../opt/openssl/include/openssl . cd -
On some systems (e.g. macOS), a compiled file is placed in a path that Bio::DB::BigFile cannot find. You can correct this with:
ln -s $KENT_SRC/lib/x86_64/* $KENT_SRC/lib/
We'll now use cpanm to install the perl module for Bio::DB::BigFile itself. See above for guidance on this. In this example we're going to install the module to a path within your home directory. In order to do this we must modify the paths that perl looks in to find modules by adding to the PERL5LIB environment module. To make this change permanent you must add the export line to your $HOME/.bashrc or $HOME/.profile.
mkdir -p $HOME/cpanm export PERL5LIB=$PERL5LIB:$HOME/cpanm/lib/perl5 cpanm -l $HOME/cpanm Bio::DB::BigFile
If you are prompted for the path to the kent source tree, that means something didn't go right in the compilation above. Double check that $KENT_SRC/lib/jkweb.a exists and is not found instead at e.g. $KENT_SRC/lib/x86_64/jkweb.a. You may copy or link the file (and the other files in that directory) to the former path.
ln -s $KENT_SRC/lib/x86_64/* $KENT_SRC/lib/
You should now be able to successfully run the appropriate test in the VEP package:
perl -Imodules t/AnnotationSource_File_BigWig.t
Installing VEP on macOS is slightly trickier than other Linux-based systems, and will require additional dependancies.
These instructions will guide you through the setup of Perlbrew, Homebrew, MySQL and other dependancies that will allow for a clean installation of VEP on your macOS system.
These instructions have been tested on macOS High Sierra (10.13) and macOS Sierra (10.12).
Older versions may require additional tweaks, however we shall endeavouXcoder to keep these instructions up to date for future versions of MacOS.
We advise using the Docker or Singularity images for VEP if you are having issues installing VEP in Apple Silicon (M1, M2, etc.) Macs.
List of prerequisites: Xcode, GCC, Perlbrew, Cpanm, Homebrew, mysql, DBI, DBD::mysql (version <=4.050)
Xcode and GCCVEP requires Xcode and GCC for installation purposes. Fortunately, recent versions of macOS will look for (and attempt to install if required) both of these when you run the following command:
gcc -vPerlbrew
We recommend using Perlbrew to install a new version of Perl on your mac, to prevent messing with the vendor perl too much. This can be done with the following command:
curl -L http://install.perlbrew.pl | bash echo 'source $HOME/perl5/perlbrew/etc/bashrc' >> ~/.bash_profile
At this point, PLEASE RESTART YOUR TERMINAL WINDOW to allow for the perlbrew changes to take effect.
We recommend installing Perl version 5.26.2 to run VEP, and installing cpanm to handle the installation of perl modules.
These steps can be completed with the commands:
perlbrew install -j 5 --as 5.26.2 --thread --64all -Duseshrplib perl-5.26.2 --notest perlbrew switch 5.26.2 perlbrew install-cpanmHomebrew
This package management system for macOS would make the installation of the next prerequisite (i.e. xs) easier.
/usr/bin/ruby -e "$(curl -fsSL https://raw.githubusercontent.com/Homebrew/install/master/install)"xz
VEP requires the installation of xz, a data-compression utility. The easiest way to install the xz package is through homebrew:
brew install xzMySQL
In order to connect to the Ensembl databases, a collection of MySQL related dependancies are required. Fortunately, these can be installed neatly with Homebrew and Cpanm:
brew install mysql cpanm DBI cpanm DBD::mysql@4.050
On some versions of macOS, the VEP installer fails to cleanly install BioPerl, so a manual install will prevent issues:
curl -O https://cpan.metacpan.org/authors/id/C/CJ/CJFIELDS/BioPerl-1.6.924.tar.gz
tar zxvf BioPerl-1.6.924.tar.gz
echo 'export PERL5LIB=${PERL5LIB}:##PATH_TO##/bioperl-1.6.924' >> ~/.bash_profile
where ##PATH_TO##/bioperl-1.6.924 refers to the location of the newly unzipped BioPerl directory.
Installing the following Perl modules with cpanm will allow for full VEP functionality:
cpanm Test::Differences Test::Exception Test::Perl::Critic Archive::Zip PadWalker Error Devel::Cycle Role::Tiny::With Module::Build LWP List::MoreUtils export DYLD_LIBRARY_PATH=/usr/local/mysql/lib/:$DYLD_LIBRARY_PATH
And that should be that! You should now be able to install VEP using the installer:
git clone https://github.com/ensembl/ensembl-vep cd ensembl-vep perl INSTALL.pl --NO_TESTUsing VEP in Windows
VEP was developed as a command-line tool, and as a Perl script its natural environment is a Linux system. However, there are several ways you can use VEP on a Windows machine.
You may also consider using VEP's web or REST interfaces.
Using a virtual machine you can run a virtual Linux system in a window on your machine. There are two ways to do this:
If Perl is installed on Windows, VEP can be setup. However this may require installation of dependent modules. We recommend using Docker to run VEP on Windows.
Navigate to the directory where you unpacked the VEP package, e.g.
cd Downloads/ensembl-vep-release-114
Run INSTALL.pl with --NO_HTSLIB and --NO_TEST; you will see some warnings about the "which" command not being available (these will also appear when running VEP and can be ignored).
perl INSTALL.pl --NO_HTSLIB --NO_TEST
Docker allows running applications in virtualised containers. The VEP Docker image is available from DockerHub: VEP in DockerHub
After installing Docker, download the VEP Docker image:
docker pull ensemblorg/ensembl-vep
To download cache files and other data with VEP Docker, we recommend mounting a directory from your local (host) machine to folder /data from the Docker image. For instance:
mkdir $HOME/vep_data docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep
In the example above, data in $HOME/vep_data will be accessible by both the local machine and VEP Docker. The Ensembl VEP API, plugins and their dependencies (e.g. Perl APIs, Bio::DB::HTS, htslib, ...) are already installed in the image.
In some distributions (e.g. CentOS, Fedora, Red Hat Enterprise Linux) Docker daemon requires root privileges (i.e. needs to prefix the command with sudo), which might cause read/write issues to the mounted volume.
One solution is to use the option :Z within the Docker -v option (only from docker 1.7.0):
sudo docker run -t -i -v $HOME/vep_data:/data:Z ensemblorg/ensembl-vep
An other solution is to change the read/write access of the mounted volume ($HOME/vep_data):
chmod -R a+rwx $HOME/vep_data
You can run the INSTALL.pl script to install the cache and FASTA files:
docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep INSTALL.pl
The above process may also be performed in one command; for example, to set up the cache and corresponding FASTA for human GRCh38:
docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep INSTALL.pl -a cf -s homo_sapiens -y GRCh38
The installer downloads VEP data to the mounted directory (e.g., $HOME/vep_data). The downloaded data will be automatically detected as long as its folder is mounted when running VEP:
docker run -v $HOME/vep_data:/data ensemblorg/ensembl-vep vep -i examples/homo_sapiens_GRCh38.vcf --cache
Here is an example on running VEP with data from folder $HOME/vep_data in the local machine (provided that the cache has been downloaded to that folder):
docker run -v $HOME/vep_data:/data ensemblorg/ensembl-vep \
vep --cache --offline --format vcf --vcf --force_overwrite \
--input_file input/my_input.vcf \
--output_file output/my_output.vcf \
--custom file=custom/my_extra_data.bed,short_name=BED_DATA,format=bed,type=exact,coords=1 \
--plugin NMD
Please avoid using absolute paths to data as the paths inside the container differ from your local machine.
Update your Docker container
docker pull ensemblorg/ensembl-vep
Update your cache
# Install the new cache through the VEP INSTALL.pl script (see "Cache installation" section above) docker run -t -i -v $HOME/vep_data:/data ensemblorg/ensembl-vep INSTALL.pl -a c # Or install the cache manually cd $HOME/vep_data curl -O https://ftp.ensembl.org/pub/release-114/variation/vep/homo_sapiens_vep_114_GRCh38.tar.gz tar xzf homo_sapiens_vep_114_GRCh38.tar.gz
Due to root requirements for the Docker daemon, using the Docker container for VEP is not always possible to HPC users. Singularity, an alternative containerisation tool, does not assume that you have a system where you are the root user. This has led to increased popularity in HPC contexts due to increased access rights flexibility.
After installing Singularity, VEP may be used with Singularity based on the VEP Docker image from DockerHub:
The following is a brief example showing how to use a directory on your local (host) machine to store cache data for VEP.
The Ensembl VEP API, plugins and their dependencies (e.g. Perl APIs, Bio::DB::HTS, htslib, ...) are already installed in the image.
You can run the INSTALL.pl script to install the Cache data and FASTA files. For example, to set up the cache and corresponding FASTA for human GRCh38 in your local folder $HOME/vep_data:
The installer downloads data to the specified directory (e.g., $HOME/vep_data). When running VEP via Singularity, point to this directory using --dir:
Here is an example on running VEP with data from folder $HOME/vep_data in the local machine (provided that the cache has been downloaded to that folder):
We offer a Nextflow VEP pipeline that aims to run VEP using simple parallelisation. The pipeline is deployable on an individual Linux machine or on computing clusters running LSF, SLURM or other workload managers.
To run the pipeline in a system with Nexflow installed, you will need to prepare a vep.ini config file. Here are some examples commands to run the Nextflow VEP pipeline:
For a full list of supported profiles, as well as more instructions on setting up and running the pipeline, please refer to the Nextflow VEP instructions.
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