GWAS Target Finder

A full-stack application for identifying protein-coding genes near significant genetic variants (SNPs) associated with a specified trait or disease, and checking if these genes are known drug targets.

Project Overview

This project consists of two main components:

1. Backend (Node.js/Express.js): A RESTful API that integrates data from multiple bioinformatics databases.
2. Frontend (Next.js): A user-friendly interface for searching and displaying results.

The application helps researchers identify potential therapeutic targets by:

• Fetching GWAS SNPs associated with specific traits
• Mapping SNPs to genomic coordinates
• Finding nearby protein-coding genes
• Checking which genes are known drug targets
• Displaying the results in an interactive format

Backend

Technologies Used

• Node.js & Express.js: Core server framework
• Axios: For external API requests
• Winston: For structured logging
• Express Validator: For input validation
• Express Rate Limit: For API protection

Features

• GWAS Catalog Integration: Fetches SNPs associated with traits
• Ensembl API Integration: Maps SNPs to genomic locations and finds nearby genes
• Open Targets Integration: Checks if genes are drug targets
• Caching System: Reduces redundant API calls
• Error Handling: Comprehensive error management
• Rate Limiting: Prevents API abuse

API Endpoints

• GET /: Health check endpoint
• POST /api/find-targets: Main endpoint for finding genes near SNPs

Frontend

Technologies Used

• Next.js: React framework for the web interface
• TypeScript: For type safety
• Tailwind CSS: For styling
• shadcn/ui: Modern UI component library
• React Query: For data fetching
• Recharts: For data visualization

Features

• Search Interface: User-friendly search by trait or EFO ID
• Results View: Interactive table with sorting and filtering
• Gene Details: Detailed information about each gene
• External Resources: Quick links to Ensembl, Open Targets, etc.
• Responsive Design: Works on various screen sizes

Getting Started

Prerequisites

• Node.js 16.x or later
• npm or yarn

Backend Setup

# Clone the repository
git clone https://github.com/yourusername/gwas-target-finder.git
cd gwas-target-finder/backend

# Install dependencies
npm install

# Set up environment variables
cp .env.example .env
# Edit .env with your settings

# Start development server
npm run dev

# For production
npm start

Frontend Setup

# Navigate to frontend directory
cd ../frontend

# Install dependencies
npm install

# Set up environment variables
cp .env.example .env.local
# Update API URL if needed

# Start development server
npm run dev

# For production
npm run build
npm start

Usage

1. Access the frontend application (default: http://localhost:3000)
2. Enter a trait name or EFO ID (e.g., "Type 2 diabetes" or "EFO_0001360")
3. Optionally adjust p-value threshold and genomic window size
4. View the results in the interactive table
5. Click on any gene to see detailed information

Example Data

The application returns data in the following format:

{
  "results": [
    {
      "gwas_snp": "rs9497975",
      "snp_location": "6:148226666",
      "nearby_gene_symbol": "SASH1",
      "nearby_gene_ensembl_id": "ENSG00000111961",
      "is_drug_target": false
    },
    {
      "gwas_snp": "rs2282978",
      "snp_location": "7:92635096",
      "nearby_gene_symbol": "CDK6",
      "nearby_gene_ensembl_id": "ENSG00000105810",
      "is_drug_target": true
    }
  ]
}

External APIs Used

1. EBI GWAS Catalog REST API

   • Base URL: https://www.ebi.ac.uk/gwas/rest/api
   • Used to fetch SNPs associated with a trait

2. Ensembl REST API

   • Base URL: https://rest.ensembl.org
   • Used to map SNPs to genomic locations and identify nearby genes

3. Open Targets Platform GraphQL API

   • URL: https://api.platform.opentargets.org/api/v4/graphql
   • Used to check if genes are known drug targets

Architecture

gwas-target-finder/
├── backend/
│   ├── src/
│   │   ├── config/         # Configuration settings
│   │   ├── controllers/    # Request handlers
│   │   ├── middleware/     # Express middleware
│   │   ├── routes/         # API route definitions
│   │   ├── services/       # Business logic and API clients
│   │   ├── utils/          # Helper utilities
│   │   └── index.js        # Entry point
│   ├── .env                # Environment variables
│   └── package.json        # Project metadata
│
└── frontend/
    ├── components/         # React components
    │   ├── gwas/           # Domain-specific components
    │   ├── layout/         # Layout components
    │   └── ui/             # UI components
    ├── lib/                # Utilities and API clients
    ├── app/                # Next.js app router
    ├── public/             # Static assets
    ├── .env.local          # Environment variables
    └── package.json        # Project metadata

Future Enhancements

• Database integration for saving search results
• User authentication for personalized features
• Advanced filtering options
• Bulk search capabilities
• Integration with additional genomic databases

License

MIT

Acknowledgements

• European Bioinformatics Institute (EBI) for the GWAS Catalog
• Ensembl for genomic data
• Open Targets Platform for drug target information

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For questions or issues, please create an issue on the GitHub repository.