AlphaGenome MCP Server

Instructions

Implementation Reference

• src/tools.ts:604-624 (schema)

  Tool schema definition including input validation and description.

  export const ANNOTATE_REGULATORY_CONTEXT_TOOL: Tool = {
    name: 'annotate_regulatory_context',
    description: `Provide comprehensive regulatory annotation for a variant.
  
  Returns detailed regulatory context including all modalities.
  
  Perfect for: variant annotation pipelines, comprehensive reports.
  
  Example: "Annotate regulatory context of chr7:12345678C>A"`,
    inputSchema: {
      type: 'object',
      properties: {
        chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
        position: { type: 'number', minimum: 1 },
        ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
        alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
        tissue_type: { type: 'string' },
      },
      required: ['chromosome', 'position', 'ref', 'alt'],
    },
  };

• src/tools.ts:709-730 (registration)

  Tool registration in the ALL_TOOLS array used by MCP listTools handler.

  export const ALL_TOOLS: Tool[] = [
    PREDICT_VARIANT_TOOL,
    BATCH_SCORE_TOOL,
    ASSESS_PATHOGENICITY_TOOL,
    PREDICT_TISSUE_SPECIFIC_TOOL,
    COMPARE_VARIANTS_TOOL,
    PREDICT_SPLICE_IMPACT_TOOL,
    PREDICT_EXPRESSION_IMPACT_TOOL,
    ANALYZE_GWAS_LOCUS_TOOL,
    COMPARE_ALLELES_TOOL,
    BATCH_TISSUE_COMPARISON_TOOL,
    PREDICT_TF_BINDING_IMPACT_TOOL,
    PREDICT_CHROMATIN_IMPACT_TOOL,
    COMPARE_PROTECTIVE_RISK_TOOL,
    BATCH_PATHOGENICITY_FILTER_TOOL,
    COMPARE_VARIANTS_SAME_GENE_TOOL,
    PREDICT_ALLELE_SPECIFIC_EFFECTS_TOOL,
    ANNOTATE_REGULATORY_CONTEXT_TOOL,
    BATCH_MODALITY_SCREEN_TOOL,
    GENERATE_VARIANT_REPORT_TOOL,
    EXPLAIN_VARIANT_IMPACT_TOOL,
  ];

• src/index.ts:250-256 (handler)

  MCP server request handler for the tool call.

  case 'annotate_regulatory_context': {
    const params = validateInput(variantPredictionSchema, args) as VariantPredictionParams;
    const result = await getClient().annotateRegulatoryContext(params);
    return {
      content: [{ type: 'text', text: JSON.stringify(result, null, 2) }],
    };
  }

• scripts/alphagenome_bridge.py:600-621 (handler)

  Core tool implementation that performs regulatory context annotation using AlphaGenome predictions.

  def annotate_regulatory_context(client, params: Dict[str, Any]) -> Dict[str, Any]:
      """Add regulatory annotations to variant."""
      result = predict_variant_effect(client, params)
  
      # Determine regulatory context from predictions
      predictions = result['predictions']
      context = []
  
      if predictions.get('rna_seq', {}).get('fold_change', 0) != 0:
          context.append('expression_QTL')
      if predictions.get('splice', {}).get('delta', 0) > 0.1:
          context.append('splice_site')
      if predictions.get('tf_binding'):
          context.append('TF_binding_site')
  
      return {
          'variant': result['variant'],
          'regulatory_context': context,
          'predictions': predictions,
          'impact_level': result['interpretation']['impact_level']
      }

• src/alphagenome-client.ts:424-431 (helper)

  Client wrapper method that invokes the Python bridge for the tool action.

  async annotateRegulatoryContext(params: VariantPredictionParams): Promise<any> {
    try {
      return await this.callPythonBridge('annotate_regulatory_context', params);
    } catch (error) {
      if (error instanceof ApiError) throw error;
      throw new ApiError(`Regulatory context annotation failed: ${error}`, 500);
    }
  }