FORGEdb

FORGEdb is an online tool designed to aid interpretation of genetic variants associated with diseases, for example variants analyzed in genome-wide association studies (GWAS). Its purpose is to annotate individual variants to identify relevant alleles and target genes.

The platform provides integrated data on individual genetic variants, including associated regulatory elements, transcription factor binding sites, and target genes. This information, derived from a wide range of biological samples, presents a thorough examination of the regulatory context for each variant at the tissue and cell type level. Data sources include Combined Annotation Dependent Depletion (CADD) scores, expression quantitative trait loci (eQTLs), activity-by-contact (ABC) interactions, and transcription factor (TF) motifs.

Notably, FORGEdb introduces a unique scoring system, the FORGEdb score. This score evaluates the functional importance of genetic variants, helping researchers prioritize variants for functional validation. It uses extensive datasets, including those from ENCODE, Roadmap Epigenomics, and BLUEPRINT consortia. With FORGEdb, researchers can quickly analyze different genomic variants and accelerate their research on disease-associated mechanisms.

Resources

• FORGEdb: https://forgedb.cancer.gov
• FORGEdb Paper: https://doi.org/10.1101/2022.11.14.516365
• FORGE2: https://forge2.altiusinstitute.org

Hosting FORGEdb on a Static File Server

Prerequisites

Building

• git
• node.js

Hosting

• Any static file server. The example instructions use Apache.

Instructions

Building and hosting the API

Each dataset is available for download at the following urls:

Dataset	Version	URL	Notes
abc	v1.0	https://forgedb.cancer.gov/api/abc/v1.0/abc.forgedb.csv.gz
cadd	v1.0	https://forgedb.cancer.gov/api/cadd/v1.0/cadd.forgedb.csv.gz
cato	v1.0	https://forgedb.cancer.gov/api/cato/v1.0/cato.forgedb.csv.gz
closest_gene	v1.0	https://forgedb.cancer.gov/api/closest_gene/v1.0/closest_gene.forgedb.csv.gz
eqtlgen	v1.0	https://forgedb.cancer.gov/api/eqtlgen/v1.0/eqtlgen.forgedb.csv.gz
forge2.blueprint	v1.0	https://forgedb.cancer.gov/api/forge2.blueprint/v1.0/forge2.blueprint.forgedb.csv.gz
forge2.encode	v1.0	https://forgedb.cancer.gov/api/forge2.encode/v1.0/forge2.encode.forgedb.csv.gz
forge2.erc	v1.0	https://forgedb.cancer.gov/api/forge2.erc/v1.0/forge2.erc.forgedb.csv.gz
forge2.erc2-chromatin15state-all	v1.0	https://forgedb.cancer.gov/api/forge2.erc2-chromatin15state-all/v1.0/forge2.erc2-chromatin15state-all.{0-9}.forgedb.csv.gz	{0-9} indicates this dataset is split into 10 parts
forge2.erc2-DHS	v1.0	https://forgedb.cancer.gov/api/forge2.erc2-DHS/v1.0/forge2.erc2-DHS.forgedb.csv.gz
forge2.erc2-H3-all	v1.0	https://forgedb.cancer.gov/api/forge2.erc2-H3-all/v1.0/forge2.erc2-H3-all.{0-9}.forgedb.csv.gz	{0-9} indicates this dataset is split into 10 parts
forge2.forge2tf	v1.0	https://forgedb.cancer.gov/api/forge2tf/v1.0/forge2tf.forgedb.csv.gz
gtex	v1.0	https://forgedb.cancer.gov/api/gtex/v1.0/gtex.forgedb.csv.gz
zoonomia	v1.0	https://forgedb.cancer.gov/api/zoonomia/v1.0/zoonomia.forgedb.csv.gz
encode4.crispr.sgrna	v1.0	https://forgedb.cancer.gov/api/encode4.crispr.sgrna/v1.0/encode4.crispr.sgrna.forgedb.csv.gz

1. Clone the repository: git clone https://github.com/CBIIT/nci-webtools-dceg-forgedb.git
2. Under your static file server's document root, create an api folder under which you wish to host the FORGEdb api.
3. Copy the contents of the client/public/api folder to the api folder you created in step 2.
4. Download source datasets from the table above to the appropriate folder. For example, place abc.forgedb.csv.gz under api/abc/v1.0/.
5. Navigate to the repository's database folder
6. Run npm install to install dependencies
7. For each dataset, execute the import.js script. For example: node import.js $DOCUMENT_ROOT/api/abc/v1.0/abc.forgedb.csv.gz

Building and hosting the API Client (Website)

1. Clone the repositrory: git clone https://github.com/CBIIT/nci-webtools-dceg-forgedb.git
2. Navigate to the client folder and run npm install && npm run build to generate the out folder. If your api is served under a subpath (eg: https://your_hostname/your_subpath/api/), specify the subpath as the NEXT_PUBLIC_BASE_PATH environment variable before building (eg: export NEXT_PUBLIC_BASE_PATH=/your_subpath).
3. Upload the out folder to your static file server's document root, ensuring that you do not overwrite the contents of the api folder.

Hosting FORGEdb on AWS S3 using Cloudfront

AWS S3/Cloudfront is a cost-effective, high-performance method of hosting FORGEdb. The recommended approach is to split the API and website code across two S3 Buckets so they can be managed independently.

1. Create or log in to an AWS Account
2. Create two S3 buckets (eg: ${org-name}-forgedb-api, ${org-name}-forgedb-website)
3. Create a Cloudfront distribution with an /api origin and a default origin. The /api origin should be served from ${$org-name}-forgedb-api, and the default origin should be served from ${org-name}-forgedb-website
4. Build the website code and push it to the $org-name-forgedb-website bucket
5. Copy the client/public/api folder to an api folder under the $org-name-forgedb-api bucket
6. Download the forgedb source files above
7. Upload each source file to the appropriate folder. For example, place abc.forgedb.csv.gz under api/abc/v1.0/.
8. Navigate to the repository's database folder
9. Run npm install to install dependencies
10. For each dataset, execute the import.js script. For example: node import.js s3://$org-name-forgedb-api/api/abc/v1.0/abc.forgedb.csv.gz. Ensure your environment has s3 credentials configured.