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HTS Bioinf - Update of external annotation data


This document describes the procedures for generating external annotation data sets for Anno.

Data sources

The instructions for generating the annotation data sets are coordinated by Anno and Anno-targets's datasets.json files. The repository of competence for each data source is shown in the table below together with the agreed respective update frequency.

Data sources Repository Updates
ClinVar (and PubMed db) Anno monthly
HGMD (and PubMed db) Anno-targets quarterly
wgsDB Anno-targets quarterly
VEP Anno yearly
inDB Anno-targets yearly
gnomAD, SeqRepo, UTA, RefSeq Anno irregularly
gnomAD-MT, gnomAD-SV, SweGen-SV, AnnotSV Anno-targets irregularly

For data sources with irregular updates, we will check every quarter for new releases, and update whenever there is a suitable and significant one.

Update Procedure


All credentials required by Anno to manage external annotation data sets are expected to be stored in a credentials file, provided to Anno's Makefile via the environment variable DB_CREDS.

DigitalOcean (DO)   -   To download and upload data to DigitalOcean's OUSAMG project, a DO access key and its corresponding secret are required. Directions for generating these credentials are available here. Store your key and secret as environment variables in the DB_CREDS file (which we assume will be set to $HOME/.db_creds) as follows:


HGMD   -   HGMD credentials are required to download HGMD data. Store your HGMD user name and password as environment variables in the DB_CREDS file as follows:


NCBI   -   An ENTREZ API token is necessary to download bulk NCBI data. Follow the instructions here and here to obtain a token and add it to the DB_CREDS file as follows:


Automatic data generation

In the following, we will assume a credentials file .db_creds to exist in $HOME.

  1. Clone the relevant repository (i.e., ella-anno or anno-targets, refer to the table above).

  2. Update datasets.json with the version you wish to generate. If required (which is rare), modify the generate commands accordingly.

  3. make build-annobuilder.

  4. make generate[-amg]-package DB_CREDS=$HOME/.db_creds PKG_NAME=<package name> (include -amg for anno-targets data sources, check the Makefile if in doubt, make help may help).

  5. make upload[-amg]-package DB_CREDS=$HOME/.db_creds PKG_NAME=<package_name> (include -amg for anno-targets data sources, check the Makefile if in doubt, make help may help).

    For HGMD updates you will need to supply the location of the reference FASTA file as FASTA=/path/to/fasta. The following make command can be used to download it from DO.

    make download-anno-package DB_CREDS=$HOME/.db_creds PKG_NAME=fasta
  6. Commit and push the changes to datasets.json in an aptly named branch (refer to a pre-existing issue in the respective repository if applicable) and file a MR. Use the merge request template data_mr_template, which proposes basic sanity checks for the newly generated data.

  7. Once the MR is approved, merge your branch into dev.

  8. After merging, follow the Release and deploy procedure for anno system.

Update literature reference database

In ELLA, we aim to keep data for all PubMed references present in either HGMD or ClinVar. These PubMed ids are generated as line-separated text files in the HGMD or ClinVar data directories.

  1. Clone the anno-targets repository
  2. make download-amg-package PKG_NAME=hgmd DB_CRES=$HOME/.db_creds
  3. make download-anno-package PKG_NAME=clinvar DB_CRES=$HOME/.db_creds
  4. cat anno-data/variantDBs/*/*_pubmed_ids.txt | sort -n | uniq >pubmed_ids.txt

The next steps are to download reference details for all these PubMed ids:

  1. Preparation. Because some of the operations below use git submodule under the hood, it is recommended to set your ssh in advance, e.g.

    eval $(ssh-agent -s)
  2. Clone the ELLA repository

  3. Copy pubmed_ids.txt into the ELLA directory
  4. Access ella-cli via docker container: docker compose run -e LOGPATH=/tmp -u $(id -u):$(id -g) --no-deps -it --entrypoint /bin/bash --build apiv1
  5. ella-cli references fetch pubmed_ids.txt (this will take some time)
  6. Import the file created in the previous step (references_YYMMDD.txt) to TSD see wiki for tacl
  7. Deposit the references in the ELLA database:

    # TSD
    ella-cli deposit references "<path to references_YYMMDD.txt>"
    7. Delete the imported file used to deposit the references