Variant-Linker

Introduction

Variant-Linker is a command-line interface (CLI) tool designed to facilitate the retrieval of genetic variant annotations. It integrates with Ensembl's Variant Recoder and Variant Effect Predictor (VEP) REST APIs to provide a streamlined process for obtaining detailed annotations for a given genetic variant.

Features

• Variant Translation: Converts genetic variant inputs into various formats to all possible variant IDs and HGVS notations.
• VEP Annotations: Retrieves detailed variant annotations from the VEP API.
• Filtering: Filters VEP annotations based on transcript specifications.
• Modular Design: Structured to facilitate the reuse of core functionalities in other projects.
• Extensibility: Prepared for future extensions to include local installations of VEP and Variant Recoder.
• Output Customization: Users can specify the output format (e.g., JSON, CSV).
• VCF Handling: Detects and processes VCF formatted input, converting it to the necessary format for Ensembl region-based annotation.
• Configuration File Support: Allows users to provide parameters through a structured configuration file.

Installation

Before installing Variant-Linker, ensure you have Node.js and npm (Node Package Manager) installed on your system.

To set up Variant-Linker, follow these steps:

1. Clone the repository:

   git clone https://github.com/your-github-username/variant-linker.git
   cd variant-linker

2. Install dependencies:

   npm install

3. Link the package globally (optional but recommended):

   npm link

Usage

After installation, you can run Variant-Linker using the following command:

variant-linker --variant <variant_input> --output <output_format> [--debug]

Command-Line Options

• --config, -c: Path to the configuration file.
• --variant, -v: Specify the genetic variant to be analyzed. This can be provided via command line or configuration file.
• --output, -o: Define the desired output format (e.g., JSON, CSV). Default is JSON.
• --save, -s: Filename to save the results. If not specified, results will be printed to the console.
• --debug, -d: Enable debug mode for detailed logging. This is optional and is not enabled by default.
• --vep_params, -vp: Optional parameters for VEP annotation in key=value format, separated by commas (default: "CADD=1").
• --recoder_params, -rp: Optional parameters for Variant Recoder in key=value format, separated by commas (default: "vcf_string=1").
• --scoring_config_path, -scp: Path to the scoring configuration directory.

Configuration File

Variant-Linker can accept a JSON configuration file to specify parameters. Command-line parameters will override configuration file parameters if both are provided.

Example Configuration File (example_input.json):

{
  "variant": "ENST00000366667:c.803C>T",
  "output": "JSON",
  "save": "output/example_output.json",
  "debug": 3,
  "scoring_config_path": "scoring/meta_score/"
}

VCF Handling

Variant-Linker can detect and process variants provided in VCF format. When a VCF formatted variant is detected, the tool:

• Converts the VCF notation to Ensembl region and allele format.
• Uses the converted format to fetch annotations via the VEP API.

VCF Format Example

• Input: 1-65568-A-C
• Ensembl region format: 1:65568-65568:1
• Allele: C

Example Usage

Using command-line parameters:

variant-linker --variant 'ENST00000366667:c.803C>T' --output JSON

Using a configuration file:

variant-linker --config example_input.json

Contributing

Contributions to Variant-Linker are welcome. Please feel free to fork the repository, make your changes, and submit a pull request.

License

This project is licensed under the MIT License.

Acknowledgements

This tool utilizes the Ensembl Variant Recoder and Variant Effect Predictor APIs, provided by the Ensembl project.