// src/tools.ts
import { Tool } from '@modelcontextprotocol/sdk/types.js';
/**
* MCP Tool Definitions for AlphaGenome Server
*/
export const PREDICT_VARIANT_TOOL: Tool = {
name: 'predict_variant_effect',
description: `Predict the regulatory impact of a genetic variant using AlphaGenome AI.
Powered by Google DeepMind's AlphaGenome model for accurate regulatory predictions.
Analyzes how a single nucleotide change affects:
- Gene expression (RNA-seq predictions)
- Splicing patterns
- Transcription factor binding
- Chromatin accessibility
- Histone modifications
Perfect for: variant interpretation, GWAS follow-up, clinical genomics research.
Example: "Analyze chr17:41234567A>T with AlphaGenome"`,
inputSchema: {
type: 'object',
properties: {
chromosome: {
type: 'string',
description: 'Chromosome (chr1-chr22, chrX, chrY)',
pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$',
},
position: {
type: 'number',
description: 'Genomic position (1-based, positive integer)',
minimum: 1,
},
ref: {
type: 'string',
description: 'Reference allele (A, T, G, or C)',
pattern: '^[ATGCatgc]+$',
},
alt: {
type: 'string',
description: 'Alternate allele (A, T, G, or C)',
pattern: '^[ATGCatgc]+$',
},
output_types: {
type: 'array',
items: {
type: 'string',
enum: [
'rna_seq',
'cage',
'splice',
'histone',
'tf_binding',
'dnase',
'atac',
'contact_map',
],
},
description: 'Optional: specific analyses to run (default: all)',
},
tissue_type: {
type: 'string',
description: 'Optional: tissue context (UBERON term, e.g., "UBERON:0001157" for brain)',
},
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const BATCH_SCORE_TOOL: Tool = {
name: 'batch_score_variants',
description: `Score and prioritize multiple genetic variants using AlphaGenome AI.
Powered by Google DeepMind's AlphaGenome model for high-throughput variant scoring.
Analyzes up to 100 variants simultaneously and ranks them by regulatory impact.
Scoring metrics:
- rna_seq: Gene expression changes
- splice: Splicing alterations
- regulatory_impact: Combined regulatory score
- combined: All metrics weighted
Perfect for: GWAS post-analysis, VCF filtering, variant prioritization.
Example: "Score these 50 variants and show me the top 10 by regulatory impact"`,
inputSchema: {
type: 'object',
properties: {
variants: {
type: 'array',
items: {
type: 'object',
properties: {
chromosome: {
type: 'string',
description: 'Chromosome',
pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$',
},
position: {
type: 'number',
description: 'Position',
minimum: 1,
},
ref: {
type: 'string',
description: 'Reference allele',
pattern: '^[ATGCatgc]+$',
},
alt: {
type: 'string',
description: 'Alternate allele',
pattern: '^[ATGCatgc]+$',
},
variant_id: {
type: 'string',
description: 'Optional: variant identifier (e.g., rs number)',
},
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
description: 'List of variants to analyze (1-100)',
minItems: 1,
maxItems: 100,
},
scoring_metric: {
type: 'string',
enum: ['rna_seq', 'splice', 'regulatory_impact', 'combined'],
description: 'Metric to use for scoring and ranking',
},
top_n: {
type: 'number',
description: 'Number of top variants to return (default: 10, max: 100)',
minimum: 1,
maximum: 100,
},
include_interpretation: {
type: 'boolean',
description: 'Include detailed clinical interpretation (default: false)',
},
},
required: ['variants', 'scoring_metric'],
},
};
// Group A Tools: Core Essential
export const ASSESS_PATHOGENICITY_TOOL: Tool = {
name: 'assess_pathogenicity',
description: `Comprehensive pathogenicity assessment of a genetic variant.
Evaluates variant across all regulatory modalities and provides clinical classification.
Returns:
- Pathogenicity score (0-1 scale)
- Clinical classification (pathogenic/likely_pathogenic/uncertain/likely_benign/benign)
- Evidence breakdown (expression, splicing, TF binding impacts)
Perfect for: clinical variant interpretation, pathogenicity prediction, diagnostic sequencing.
Example: "Assess pathogenicity of chr19:44908684T>C"`,
inputSchema: {
type: 'object',
properties: {
chromosome: {
type: 'string',
description: 'Chromosome (chr1-chr22, chrX, chrY)',
pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$',
},
position: {
type: 'number',
description: 'Genomic position (1-based)',
minimum: 1,
},
ref: {
type: 'string',
description: 'Reference allele',
pattern: '^[ATGCatgc]+$',
},
alt: {
type: 'string',
description: 'Alternate allele',
pattern: '^[ATGCatgc]+$',
},
tissue_type: {
type: 'string',
description: 'Optional: disease-relevant tissue (default: brain)',
},
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const PREDICT_TISSUE_SPECIFIC_TOOL: Tool = {
name: 'predict_tissue_specific',
description: `Predict variant effects across multiple tissues.
Compares regulatory impact in different tissues to identify tissue-specific effects.
Default tissues: brain, liver, heart (customizable)
Returns impact levels and expression changes for each tissue.
Perfect for: understanding tissue-specific disease mechanisms, prioritizing relevant tissues.
Example: "Compare rs429358 effects in brain, liver, and heart"`,
inputSchema: {
type: 'object',
properties: {
chromosome: {
type: 'string',
description: 'Chromosome',
pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$',
},
position: {
type: 'number',
description: 'Genomic position',
minimum: 1,
},
ref: {
type: 'string',
description: 'Reference allele',
pattern: '^[ATGCatgc]+$',
},
alt: {
type: 'string',
description: 'Alternate allele',
pattern: '^[ATGCatgc]+$',
},
tissues: {
type: 'array',
items: {
type: 'string',
},
description: 'List of tissues to test (default: brain, liver, heart)',
},
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const COMPARE_VARIANTS_TOOL: Tool = {
name: 'compare_variants',
description: `Compare two variants side-by-side.
Direct comparison of regulatory impacts between two variants.
Returns:
- Impact levels for both variants
- Expression and splicing changes
- Which variant is more severe
Perfect for: comparing candidate variants, understanding relative severity.
Example: "Compare rs429358 vs rs7412"`,
inputSchema: {
type: 'object',
properties: {
variant1: {
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]+$' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
variant2: {
type: 'object',
properties: {
chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
position: { type: 'number', minimum: 1 },
ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
},
required: ['variant1', 'variant2'],
},
};
// Group B Tools: Frequently Needed
export const PREDICT_SPLICE_IMPACT_TOOL: Tool = {
name: 'predict_splice_impact',
description: `Focus on splicing-specific effects only.
Analyzes splice sites, splice site usage, and splice junctions.
Perfect for: investigating splicing variants, understanding splice alterations.
Example: "Analyze splicing impact of chr6:41129252C>T"`,
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]+$' },
tissue_type: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const PREDICT_EXPRESSION_IMPACT_TOOL: Tool = {
name: 'predict_expression_impact',
description: `Focus on gene expression effects only.
Analyzes RNA-seq and CAGE predictions for expression changes.
Perfect for: eQTL analysis, expression-related variants.
Example: "Analyze expression impact of rs744373"`,
inputSchema: {
type: 'object',
properties: {
chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
position: { type: 'number', minimum: 1 },
ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
tissue_type: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const ANALYZE_GWAS_LOCUS_TOOL: Tool = {
name: 'analyze_gwas_locus',
description: `Analyze all variants in a GWAS locus.
Ranks variants by regulatory impact for fine-mapping and causal variant identification.
Perfect for: GWAS follow-up, fine-mapping, identifying causal variants.
Example: "Analyze GWAS locus with 10 variants"`,
inputSchema: {
type: 'object',
properties: {
variants: {
type: 'array',
items: {
type: 'object',
properties: {
chromosome: { type: 'string' },
position: { type: 'number' },
ref: { type: 'string' },
alt: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
minItems: 1,
},
chromosome: { type: 'string' },
start: { type: 'number' },
end: { type: 'number' },
},
required: ['variants'],
},
};
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]+$' },
minItems: 2,
},
},
required: ['chromosome', 'position', 'ref', 'alts'],
},
};
export const BATCH_TISSUE_COMPARISON_TOOL: Tool = {
name: 'batch_tissue_comparison',
description: `Analyze multiple variants across multiple tissues.
Efficient batch analysis of variants × tissues combinations.
Perfect for: large-scale tissue-specificity studies.
Example: "Test 10 variants in brain, liver, heart"`,
inputSchema: {
type: 'object',
properties: {
variants: {
type: 'array',
items: {
type: 'object',
properties: {
chromosome: { type: 'string' },
position: { type: 'number' },
ref: { type: 'string' },
alt: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
minItems: 1,
},
tissues: {
type: 'array',
items: { type: 'string' },
minItems: 1,
},
},
required: ['variants', 'tissues'],
},
};
// Group C Tools: Occasionally Useful
export const PREDICT_TF_BINDING_IMPACT_TOOL: Tool = {
name: 'predict_tf_binding_impact',
description: `Focus on transcription factor binding effects only.
Analyzes TF binding site changes using ChIP-seq predictions.
Perfect for: TF binding site variants, regulatory element analysis.
Example: "Analyze TF binding impact of chr1:12345678G>A"`,
inputSchema: {
type: 'object',
properties: {
chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
position: { type: 'number', minimum: 1 },
ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
tissue_type: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const PREDICT_CHROMATIN_IMPACT_TOOL: Tool = {
name: 'predict_chromatin_impact',
description: `Focus on chromatin accessibility effects only.
Analyzes DNase and ATAC-seq predictions for chromatin state changes.
Perfect for: enhancer variants, regulatory region analysis.
Example: "Analyze chromatin impact of chr2:23456789C>T"`,
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]+$' },
tissue_type: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const COMPARE_PROTECTIVE_RISK_TOOL: Tool = {
name: 'compare_protective_risk',
description: `Compare protective vs risk alleles directly.
Side-by-side comparison of alleles with opposite disease associations.
Perfect for: disease mechanism studies, therapeutic target identification.
Example: "Compare APOE protective allele vs risk allele"`,
inputSchema: {
type: 'object',
properties: {
protective_variant: {
type: 'object',
properties: {
chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
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'],
},
};
export const BATCH_PATHOGENICITY_FILTER_TOOL: Tool = {
name: 'batch_pathogenicity_filter',
description: `Filter variants by pathogenicity threshold.
Efficiently identifies pathogenic variants from large lists.
Perfect for: VCF filtering, prioritizing clinical variants.
Example: "Filter 100 variants for pathogenicity > 0.7"`,
inputSchema: {
type: 'object',
properties: {
variants: {
type: 'array',
items: {
type: 'object',
properties: {
chromosome: { type: 'string' },
position: { type: 'number' },
ref: { type: 'string' },
alt: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
minItems: 1,
},
threshold: {
type: 'number',
minimum: 0,
maximum: 1,
description: 'Pathogenicity threshold (0-1, default: 0.5)',
},
},
required: ['variants'],
},
};
export const COMPARE_VARIANTS_SAME_GENE_TOOL: Tool = {
name: 'compare_variants_same_gene',
description: `Compare multiple variants within the same gene.
Ranks variants by impact within a single gene context.
Perfect for: gene-level analysis, compound heterozygote analysis.
Example: "Compare 5 BRCA1 variants"`,
inputSchema: {
type: 'object',
properties: {
variants: {
type: 'array',
items: {
type: 'object',
properties: {
chromosome: { type: 'string' },
position: { type: 'number' },
ref: { type: 'string' },
alt: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
minItems: 2,
},
gene_name: {
type: 'string',
description: 'Optional: gene name for context',
},
},
required: ['variants'],
},
};
export const PREDICT_ALLELE_SPECIFIC_EFFECTS_TOOL: Tool = {
name: 'predict_allele_specific_effects',
description: `Analyze allele-specific regulatory effects.
Detailed analysis of how each allele affects gene regulation differently.
Perfect for: ASE analysis, imprinting studies.
Example: "Analyze allele-specific effects of chr15:67890123A>G"`,
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'],
},
};
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]+$' },
tissue_type: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const BATCH_MODALITY_SCREEN_TOOL: Tool = {
name: 'batch_modality_screen',
description: `Screen variants across specific regulatory modalities.
Efficiently tests multiple variants for specific regulatory effects.
Perfect for: targeted regulatory screens, modality-specific studies.
Example: "Screen 20 variants for splicing effects"`,
inputSchema: {
type: 'object',
properties: {
variants: {
type: 'array',
items: {
type: 'object',
properties: {
chromosome: { type: 'string' },
position: { type: 'number' },
ref: { type: 'string' },
alt: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
minItems: 1,
},
modality: {
type: 'string',
enum: ['expression', 'splicing', 'tf_binding', 'chromatin'],
description: 'Regulatory modality to screen',
},
},
required: ['variants', 'modality'],
},
};
export const GENERATE_VARIANT_REPORT_TOOL: Tool = {
name: 'generate_variant_report',
description: `Generate comprehensive clinical report for a variant.
Full analysis with all modalities and clinical interpretation.
Perfect for: clinical reports, diagnostic summaries.
Example: "Generate full report for chr13:32912345G>T"`,
inputSchema: {
type: 'object',
properties: {
chromosome: { type: 'string', pattern: '^chr([1-9]|1[0-9]|2[0-2]|X|Y)$' },
position: { type: 'number', minimum: 1 },
ref: { type: 'string', pattern: '^[ATGCatgc]+$' },
alt: { type: 'string', pattern: '^[ATGCatgc]+$' },
tissue_type: { type: 'string' },
},
required: ['chromosome', 'position', 'ref', 'alt'],
},
};
export const EXPLAIN_VARIANT_IMPACT_TOOL: Tool = {
name: 'explain_variant_impact',
description: `Provide human-readable explanation of variant impact.
Translates technical predictions into plain language.
Perfect for: patient reports, non-technical summaries.
Example: "Explain the impact of chr9:12345678A>C in simple terms"`,
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'],
},
};
/**
* All available tools
*/
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,
];
