AlphaGenome MCP Server

Instructions

Implementation Reference

• src/tools.ts:473-508 (schema)

  Defines the Tool object for 'compare_protective_risk' including name, description, and input schema requiring protective_variant and risk_variant objects.

  export const COMPARE_PROTECTIVE_RISK_TOOL: Tool = {
    name: 'compare_protective_risk',
    description: `Compare protective vs risk alleles directly.
  
  Side-by-side comparison of alleles with opposite disease associations.
  
  Perfect for: disease mechanism studies, therapeutic target identification.
  
  Example: "Compare APOE protective allele vs risk allele"`,
    inputSchema: {
      type: 'object',
      properties: {
        protective_variant: {
          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]+$' },
          },
          required: ['chromosome', 'position', 'ref', 'alt'],
        },
        risk_variant: {
          type: 'object',
          properties: {
            chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
            position: { type: 'number', minimum: 1 },
            ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
            alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
          },
          required: ['chromosome', 'position', 'ref', 'alt'],
        },
      },
      required: ['protective_variant', 'risk_variant'],
    },
  };

• src/tools.ts:709-730 (registration)

  Registers COMPARE_PROTECTIVE_RISK_TOOL in the ALL_TOOLS array used by the 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:221-226 (handler)

  MCP server request handler for 'compare_protective_risk' tool call, invokes AlphaGenomeClient and returns JSON-formatted result.

  case 'compare_protective_risk': {
    const result = await getClient().compareProtectiveRisk(args);
    return {
      content: [{ type: 'text', text: JSON.stringify(result, null, 2) }],
    };
  }

• src/alphagenome-client.ts:376-383 (helper)

  AlphaGenomeClient method that forwards compare_protective_risk parameters to the Python bridge via callPythonBridge.

  async compareProtectiveRisk(params: any): Promise<any> {
    try {
      return await this.callPythonBridge('compare_protective_risk', params);
    } catch (error) {
      if (error instanceof ApiError) throw error;
      throw new ApiError(`Protective vs risk comparison failed: ${error}`, 500);
    }
  }

• scripts/alphagenome_bridge.py:505-525 (handler)

  Core handler function in Python bridge that implements the tool logic by predicting variant effects for protective and risk variants and returning a comparison dictionary.

  def compare_protective_risk(client, params: Dict[str, Any]) -> Dict[str, Any]:
      """Compare protective vs risk alleles."""
      protective = params.get('protective_variant')
      risk = params.get('risk_variant')
  
      result_protective = predict_variant_effect(client, protective)
      result_risk = predict_variant_effect(client, risk)
  
      return {
          'protective': {
              'variant': result_protective['variant'],
              'impact': result_protective['interpretation']['impact_level'],
              'expression_fc': result_protective['predictions'].get('rna_seq', {}).get('fold_change', 0)
          },
          'risk': {
              'variant': result_risk['variant'],
              'impact': result_risk['interpretation']['impact_level'],
              'expression_fc': result_risk['predictions'].get('rna_seq', {}).get('fold_change', 0)
          }
      }