ga4gh.vrs 2.0.0a3

"GA4GH Variation Representation Specification (VRS) reference implementation (https://github.com/ga4gh/vrs-python/)"

vrs-python

vrs-python provides Python language support for the GA4GH Variation Representation Specification (VRS).

This repository contains several related components:

• ga4gh.core package Python language support for certain nascent standards in GA4GH. Eventually, this package should be moved to a distinct repo.

• ga4gh.vrs package Python language support for VRS.

• ga4gh.vrs.extras package Python language support for additional functionality, including translating from and to other variant formats and a REST service to similar functionality. ga4gh.vrs.extras requires access to supporting data, as described below.

• Jupyter notebooks Demonstrations of the functionality of ga4gh.vrs and ga4gh.vrs.extras in the form of easy-to-read notebooks.

VRS-Python and VRS Version Correspondence

The ga4gh/vrs-python repo embeds the ga4gh/vrs repo as a git submodule, and therefore each ga4gh.vrs package on PyPI embeds a particular version of VRS. The correspondences between the packages that are currently maintained may be summarized as:

vrs-python branch	vrs-python tag/version	vrs branch	vrs version
main (default branch)	2.x	2.0-alpha	2.x
1.x	0.8.x	1.x	1.x

⚠ Note: Only 2.x branch is being actively maintained. The 1.x branch will only be maintained for bug fixes.

⚠ Developers: See the development section below for recommendations for using submodules gracefully (and without causing problems for others!).

Previous VRS-Python and VRS Version Correspondence

The correspondences between the packages that are no longer maintained may be summarized as:

vrs-python branch	vrs-python tag/version	vrs branch	vrs version
0.6	0.6.x	1.1	1.1.x
0.7	0.7.x	1.2	1.2.x
0.9	0.9.x	metaschema-update	N/A

Pre-requisite

Python 3.10

Development

Submodules!

vrs-python embeds vrs as a submodule. When checking out vrs-python and switching branches, it is important to make sure that the submodule tracks vrs-python correctly. The recommended way to do this is git config --global submodule.recurse true. If you don't set submodule.recurse, developers and reviewers must be extremely careful to not accidentally upgrade or downgrade schemas with respect to vrs-python.

Alternatively, see misc/githooks/.

Installing for development

Fork the repo at https://github.com/ga4gh/vrs-python/ .

$ git clone --recurse-submodules [e-mail]:YOUR_GITHUB_ID/vrs-python.git
$ cd vrs-python
$ make devready

Activate the virtual environment (if not already) :

$ source venv/3.10/bin/activate

Pre-commit

We use pre-commit to check code style.

Before first commit, run:

$ pre-commit install

Testing

This package implements typical unit tests for ga4gh.core and ga4gh.vrs. This package also implements the compliance tests from vrs (vrs/validation) in the tests/validation/ directory.

$ make test

Developing VRS (the schema) too

If you want to develop the VRS schema in conjunction with vrs-python, the recommended approach for most users is to fork and clone the ga4gh/vrs repo, then set the VRS_SCHEMA_DIR environment variable to use an alternative schema location.

Installation

Install PostgreSQL

PostgreSQL is required for UTA. Ensure that PostgreSQL is installed on your system. You can download and install PostgreSQL from here or install using Homebrew.

There are macOS docs for additional assistance.

Install PostgreSQL using Homebrew

1. Install Homebrew: See the documentation for how to install.

2. Update Homebrew: Make sure Homebrew is up-to-date by running:

    brew update
   

3. Install PostgreSQL: Use the following command to install PostgreSQL:

    brew install postgresql@14
   

4. Start PostgreSQL: Once the installation is complete, you can start the PostgreSQL service using:

    brew services start postgresql
   

Installing the VRS-Python package with pip

Once PostgreSQL is installed, proceed with the following command to install the VRS-Python package:

pip install 'ga4gh.vrs[extras]'

The [extras] argument tells pip to install packages to fulfill the dependencies of the ga4gh.vrs.extras package.

Installing dependencies for ga4gh.vrs.extras

The ga4gh.vrs.extras modules are not part of the VR spec per se. They are bundled with ga4gh.vrs for development and installation convenience. These modules depend directly and indirectly on external data sources of sequences, transcripts, and genome-transcript alignments. This section recommends one way to install the biocommons tools that provide these data.

docker volume create --name=uta_vol
docker volume create --name=seqrepo_vol
docker-compose up

This should start three containers:

• seqrepo: downloads seqrepo into a docker volume and exits
• seqrepo-rest-service: a REST service on seqrepo (localhost:5000)
• uta: a database of transcripts and alignments (localhost:5432)

Check that the containers are running:

$ docker ps
CONTAINER ID        IMAGE                                    //  NAMES
86e872ab0c69        biocommons/seqrepo-rest-service:latest   //  vrs-python_seqrepo-rest-service_1
a40576b8cf1f        biocommons/uta:uta_20210129b              //  vrs-python_uta_1

Depending on your network and host, the first run is likely to take 5-15 minutes in order to download and install data. Subsequent startups should be nearly instantaneous.

You can test UTA and seqrepo installations like so:

snafu$ psql -XAt postgres://anonymous@localhost/uta -c 'select count(*) from transcript'
249909

It doesn't work!

Here are some things to try.

• Bring up one service at a time. For example, if you haven't download seqrepo yet, you might see this:

  snafu$ docker-compose up seqrepo-rest-service
  Starting vrs-python_seqrepo-rest-service_1 ... done
  Attaching to vrs-python_seqrepo-rest-service_1
  seqrepo-rest-service_1  | 2022-07-26 15:59:59 snafu seqrepo_rest_service.__main__[1] INFO Using seqrepo_dir='/usr/local/share/seqrepo/2021-01-29' from command line
  ⋮
  seqrepo-rest-service_1  | OSError: Unable to open SeqRepo directory /usr/local/share/seqrepo/2021-01-29
  vrs-python_seqrepo-rest-service_1 exited with code 1
  

Running the Notebooks

Once installed as described above, type

$ jupyter notebook --notebook-dir notebooks/

The following jupyter extensions are recommended but not required

$ pip install jupyter_contrib_nbextensions
$ jupyter contrib nbextension install --user
$ jupyter nbextension enable toc2/main

Running the Notebooks on the Terra platform

Terra is a cloud platform for biomedical research developed by the Broad Institute, Microsoft and Verily. The platform includes preconfigured environments that provide user-friendly access to various applications commonly used in bioinformatics, including Jupyter Notebooks.

We have created a public VRS-demo-notebooks workspace in Terra that contains the demo notebooks along with instructions for running them with minimal setup. To get started, see either the VRS-demo-notebooks workspace or the Terra.ipynb notebook in this repository.

Running the Notebooks with VS Code

VS Code is a code editor developed by Microsoft. It is lightweight, highly customizable, and supports a wide range of programming languages, with a robust extension system. You can download VS Code here.

1. Open VS Code: Launch Visual Studio Code. 2. Install the Jupyter Extension: Use Extensions view (Ctrl+Shift+X or ⌘+Shift+X) to install the Jupyter extension. 3. Open the Project in VS Code: Navigate to your project folder and open it in VS Code. 4. Select the Jupyter Kernel: In a notebook, click Select Kernel at the top right. Select the option where the path is venv/3.10/bin/python3. See here for more information on managing Jupyter Kernels in VS Code. 5. Run the Notebook: After selecting the kernel you can now run the notebook.

Security Note (from the GA4GH Security Team)

A stand-alone security review has been performed on the specification itself. This implementation is offered as-is, and without any security guarantees. It will need an independent security review before it can be considered ready for use in security-critical applications. If you integrate this code into your application it is AT YOUR OWN RISK AND RESPONSIBILITY to arrange for a security audit.