Here you may find all details on how to set up the MetaDome web server in your own environment.
The MetaDome webserver has only been tested for running in a Linux-based OS (tested on Ubuntu 16.04, Ubuntu 18.04 and Centos 7), but as it is fully containerized in docker it should in theory be possible to run it on any other OS. Please ensure you have the following software installed on your machine:
docker
docker-compose
You can get docker here and docker-compose here
The MetaDome web server makes use of the following data resources
MetaDome uses version v19 of Gencode for GRCH37. Available here, please download the following files:
gencode.v19.annotation.gtf
gencode.v19.annotation.gff3
gencode.v19.pc_transcripts.fa
gencode.v19.pc_translations.fa
gencode.v19.metadata.SwissProt
ucsc.gencode.v19.wgEncodeGencodeBasic.txt
Please put these in your preferred data storage folder under '/Gencode/'
MetaDome was tested with UniProt version 2016_09. Available here, please download the following files:
uniprot_sprot.dat.gz
uniprot_sprot_varsplic.fasta.gz
uniprot_sprot.fasta.gz
Unzip 'uniprot_sprot_varsplic.fasta.gz' and 'uniprot_sprot.fasta.gz' and combine them to a new file: uniprot_sprot_canonical_and_varsplic.fasta
Next you should build a blast database from this new file named 'uniprot_sprot_canonical_and_varsplic.fasta'. See here for a further explanation on how to do this if you are unfamiliar with that.
Next, put all of this in your preferred data storage folder under '/UniProt/'
MetaDome was tested with version 20180603 for GRCh37, but later versions may work as well as long as the GRCh37 remains unchanged. From here, please download the following files: clinvar.vcf.gz clinvar.vcf.gz.tbi
And put this in your preferred data storage folder under '/ClinVar/GRCh37/'
MetaDome was tested with version r2.0.2 for GRCh37, but later versions may work as well as long as the GRCh37 remains unchanged. From here, please download the following files:
gnomad.exomes.r2.0.2.sites.vcf.bgz
gnomad.exomes.r2.0.2.sites.vcf.bgz.tbi
And put this in your preferred data storage folder under '/gnomAD/'
MetaDome was tested with PFAM version 30.0. From here, please download the following files:
Pfam-A.hmm.dat.gz
Pfam-A.hmm.gz
Unzip 'Pfam-A.hmm.gz' to Pfam-A.hmm. We used a Python script (available upon request) to seperate each of the PFAM alignments contained within 'Pfam-A.hmm.dat.gz' to a folder : 'alignment/PFXXXXX/full' where XXXXX corresponds to the PFAM identifier for faster querying and the alignment is contained in the file 'full'. MetaDome webserver expects the files to be organised as such.
Put all this in your preferred data storage folder under '/PFAM/'
Clone the repository and go into the project folder:
git clone https://github.com/cmbi/metadome.git
cd metadome
Be sure to configure the correct file paths in the .env file (at the <ABSOLUTE PATH>) to correspond with your data folders.
If you are attempting to recreate the underlying database (see First time set-up below), then be sure to create an empty folder specifically to contain the MetaDome mapping PostgreSQL database at METADOME_POSTGRES_DB_DIR in the .env file.
If you are planning to expose the MetaDome server to a public adress, please make sure you get the security in order.
- Change the variable `POSTGRES_PASSWORD`, `POSTGRES_USER`, and `POSTGRES_DB` for the postgresql database in `./metadome/database.env`
- Change the variable `SECRET_KEY_CRED` in `./metadome/flask_app_credentials.py`
Otherwise you will be using default passwords and API secrets.
First you will need to build the docker-compose:
docker-compose build --force-rm --no-cache
This will build the docker containers required to run the webserver. The PostgreSQL database needs to be initialized, therefore you should run the entire webserver untill it stabilizes (e.g. no more messages pop up):
docker-compose docker-compose.yml up
When there are no further print-outs of following this command, the database should be readily initialized. You can shut down the webserver by CTRL+C keyboard command.
TROUBLE SHOOTING: If there are still print outs even after a minute or so, you will have to follow these steps:
- Stop the web server and remove volume bindings :
docker-compose down -v - Make sure the empty folder to contain the MetaDome mapping PostgreSQL database at
metadome_postgres_db:in thevolumes:section in the docker-compose.yml is empty. If not, remove all files. - Make sure no further metadome instances are running (check through
docker ps -a) - Restart the steps in first time set-up
If you get through this step correctly, you can run the following command to execute the install script that will generate the database:
docker-compose run app python install.py --build --platform=linux/amd64
Note: Launching the server this way, by creating the database from scratch, will first make it generate all mappings between gencode, swissprot and Pfam. This process, depending on your configuration, may take 2 weeks. If you require a pre-build database, do not hesitate to contact us.
If you followed the above configuration steps, you should now be able to run the webserver via the command:
docker-compose docker-compose.yml up -d
And tear it down via:
docker-compose -f docker-compose.yml stop
Please cite the MetaDome web server article :
MetaDome: Pathogenicity analysis of genetic variants
through aggregation of homologous human protein domains.
Laurens Wiel, Coos Baakman, Daan Gilissen, Joris A. Veltman,
Gert Vriend and Christian Gilissen.
Human Mutation. (2019) 1-9, 10.1002/humu.23798
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