calculate_dynamic_eqtl
Analyze how genetic variants affect gene expression across different human tissues to identify tissue-specific regulatory effects using GTEx genomics data.
Instructions
Calculate dynamic eQTL effects across tissues
Input Schema
TableJSON Schema
| Name | Required | Description | Default |
|---|---|---|---|
| gencodeId | Yes | GENCODE gene ID (e.g., ENSG00000223972.5) | |
| snpId | Yes | SNP ID (rs number or variant ID) | |
| tissueSiteDetailIds | Yes | Array of tissue site detail IDs to compare | |
| datasetId | No | GTEx dataset ID (default: gtex_v8) | gtex_v8 |
Implementation Reference
- Main handler function executing the tool logic: validates inputs, calls API, processes dynamic eQTL results including statistics and genotype-based expression summaries, formats rich text output.async calculateDynamicEQTL(args: any) { if (!args.geneId || !args.variantId || !args.tissueId) { throw new Error('geneId, variantId, and tissueId parameters are all required'); } const result = await this.apiClient.calculateDynamicEQTL({ gencodeId: args.geneId, variantId: args.variantId, tissueSiteDetailId: args.tissueId, datasetId: args.datasetId || 'gtex_v8' }); if (result.error) { return { content: [{ type: "text", text: `Error calculating dynamic eQTL: ${result.error}` }], isError: true }; } const eqtlResult = result.data; if (!eqtlResult) { return { content: [{ type: "text", text: "No dynamic eQTL result returned." }] }; } const tissueDisplayName = this.getTissueDisplayName(args.tissueId); let output = `**Dynamic eQTL Calculation**\n`; output += `Gene: **${eqtlResult.geneSymbol}** (${eqtlResult.gencodeId})\n`; output += `Variant: **${eqtlResult.variantId}**\n`; output += `Tissue: **${tissueDisplayName}**\n\n`; if (eqtlResult.error && eqtlResult.error !== 0) { output += `⚠️ **Calculation Error:** Error code ${eqtlResult.error}\n\n`; } output += `**Statistical Results:**\n`; output += `• p-value: ${eqtlResult.pValue.toExponential(2)}\n`; output += `• Normalized Effect Size (NES): ${eqtlResult.nes.toFixed(4)}\n`; output += `• t-statistic: ${eqtlResult.tStatistic.toFixed(4)}\n`; output += `• Minor Allele Frequency: ${(eqtlResult.maf * 100).toFixed(2)}%\n`; output += `• p-value threshold: ${eqtlResult.pValueThreshold.toExponential(2)}\n`; const isSignificant = eqtlResult.pValue < eqtlResult.pValueThreshold; output += `• **Significance:** ${isSignificant ? '✅ Significant' : '❌ Not significant'}\n\n`; output += `**Genotype Distribution:**\n`; output += `• Homozygous reference: ${eqtlResult.homoRefCount} samples\n`; output += `• Heterozygous: ${eqtlResult.hetCount} samples\n`; output += `• Homozygous alternate: ${eqtlResult.homoAltCount} samples\n`; const totalSamples = eqtlResult.homoRefCount + eqtlResult.hetCount + eqtlResult.homoAltCount; output += `• **Total samples:** ${totalSamples}\n\n`; if (eqtlResult.data && eqtlResult.genotypes && eqtlResult.data.length === eqtlResult.genotypes.length && eqtlResult.data.length > 0) { // Calculate expression statistics by genotype const expressionByGenotype: { [key: number]: number[] } = {}; eqtlResult.data.forEach((expr, i) => { const genotype = eqtlResult.genotypes[i]; if (!expressionByGenotype[genotype]) { expressionByGenotype[genotype] = []; } expressionByGenotype[genotype].push(expr); }); output += `**Expression by Genotype:**\n`; Object.keys(expressionByGenotype).sort().forEach(genotype => { const expressions = expressionByGenotype[parseInt(genotype)]; const mean = expressions.reduce((sum, val) => sum + val, 0) / expressions.length; const genotypeLabel = genotype === '0' ? 'Ref/Ref' : genotype === '1' ? 'Ref/Alt' : 'Alt/Alt'; output += `• ${genotypeLabel}: ${mean.toFixed(3)} TPM (${expressions.length} samples)\n`; }); } return { content: [{ type: "text", text: output }] }; }
- src/index.ts:685-691 (registration)Tool registration and dispatch in the main CallToolRequest handler, mapping tool arguments to handler method call.if (name === "calculate_dynamic_eqtl") { return await associationHandlers.calculateDynamicEQTL({ geneId: args?.gencodeId, variantId: args?.snpId, tissueId: Array.isArray(args?.tissueSiteDetailIds) && args.tissueSiteDetailIds.length > 0 ? args.tissueSiteDetailIds[0] : undefined, datasetId: args?.datasetId });
- src/types/gtex-types.ts:418-423 (schema)Type definition for input parameters used by the API client and handler.export interface CalculateDynamicEQTLParams { tissueSiteDetailId: string; gencodeId: string; variantId: string; datasetId?: string; }
- src/index.ts:273-298 (schema)Tool input schema definition provided to MCP ListToolsRequest.name: "calculate_dynamic_eqtl", description: "Calculate dynamic eQTL effects across tissues", inputSchema: { type: "object", properties: { gencodeId: { type: "string", description: "GENCODE gene ID (e.g., ENSG00000223972.5)" }, snpId: { type: "string", description: "SNP ID (rs number or variant ID)" }, tissueSiteDetailIds: { type: "array", items: { type: "string" }, description: "Array of tissue site detail IDs to compare" }, datasetId: { type: "string", description: "GTEx dataset ID (default: gtex_v8)", default: "gtex_v8" } }, required: ["gencodeId", "snpId", "tissueSiteDetailIds"] }
- src/utils/api-client.ts:529-542 (helper)API client helper method that performs the HTTP request to GTEx Portal's /association/dyneqtl endpoint.async calculateDynamicEQTL(params: CalculateDynamicEQTLParams): Promise<GTExApiResponse<DynamicEQTLResult>> { try { const queryParams = this.buildQueryParams({ tissueSiteDetailId: params.tissueSiteDetailId, gencodeId: params.gencodeId, variantId: params.variantId, datasetId: params.datasetId || 'gtex_v8' }); const response = await this.axiosInstance.get(`/association/dyneqtl?${queryParams}`); return { data: response.data }; } catch (error) { return error as GTExApiResponse<DynamicEQTLResult>; } }