AlphaGenome MCP Server

Instructions

Implementation Reference

• scripts/alphagenome_bridge.py:417-450 (handler)

  Core handler function implementing the compare_alleles tool logic: compares multiple alternate alleles at the same genomic position by calling predict_variant_effect for each and compiling results.

  def compare_alleles(client, params: Dict[str, Any]) -> Dict[str, Any]:
      """
      Compare different alleles at the same position.
      """
      chromosome = params.get('chromosome')
      position = params.get('position')
      ref = params.get('ref')
      alts = params.get('alts', [])
  
      results = {}
      for alt in alts:
          try:
              var_params = {
                  'chromosome': chromosome,
                  'position': position,
                  'ref': ref,
                  'alt': alt
              }
              result = predict_variant_effect(client, var_params)
              results[f"{ref}>{alt}"] = {
                  'impact_level': result['interpretation']['impact_level'],
                  'expression_fc': result['predictions'].get('rna_seq', {}).get('fold_change', 0),
                  'clinical_sig': result['interpretation']['clinical_significance']
              }
          except Exception as e:
              print(f"Warning: Failed for allele {alt}: {e}", file=sys.stderr)
              results[f"{ref}>{alt}"] = {'error': str(e)}
  
      return {
          'position': f"{chromosome}:{position}",
          'reference': ref,
          'allele_comparisons': results
      }

• src/index.ts:191-196 (handler)

  MCP server tool handler for 'compare_alleles': dispatches to AlphaGenomeClient.compareAlleles and formats response.

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

• src/tools.ts:368-389 (schema)

  Tool schema definition including name, description, and input validation schema for compare_alleles.

  export const COMPARE_ALLELES_TOOL: Tool = {
    name: 'compare_alleles',
    description: `Compare different alleles at the same position.
  
  Useful for understanding effects of different mutations at a hotspot position.
  
  Example: "Compare T>C vs T>G vs T>A at chr19:44908684"`,
    inputSchema: {
      type: 'object',
      properties: {
        chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
        position: { type: 'number', minimum: 1 },
        ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
        alts: {
          type: 'array',
          items: { type: 'string', pattern: '^[ATGCatgc]+$' },
          minItems: 2,
        },
      },
      required: ['chromosome', 'position', 'ref', 'alts'],
    },
  };

• src/tools.ts:709-730 (registration)

  Registration of compare_alleles tool in the ALL_TOOLS array, used by MCP server for tool listing.

  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/alphagenome-client.ts:328-335 (helper)

  Client method that bridges to Python by calling the alphagenome_bridge.py with 'compare_alleles' action.

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