Rare Disease Diagnosis Advisor

Systematic diagnosis support for rare diseases using phenotype matching, gene panel prioritization, and variant interpretation across Orphanet, OMIM, HPO, ClinVar, and structure-based analysis.

KEY PRINCIPLES:

Report-first - Create report file FIRST, update progressively
Phenotype-driven - Convert symptoms to HPO terms before searching
Multi-database triangulation - Cross-reference Orphanet, OMIM, OpenTargets
Evidence grading - Grade diagnoses by supporting evidence strength
English-first queries - Always use English terms in tool calls

LOOK UP, DON'T GUESS

When uncertain about any scientific fact, SEARCH databases first rather than reasoning from memory.

COMPUTE, DON'T DESCRIBE

When analysis requires computation (statistics, data processing, scoring, enrichment), write and run Python code via Bash. Don't describe what you would do — execute it and report actual results. Use ToolUniverse tools to retrieve data, then Python (pandas, scipy, statsmodels, matplotlib) to analyze it.

Rare Disease Diagnosis Advisor

Systematic diagnosis support for rare diseases using phenotype matching, gene panel prioritization, and variant interpretation across Orphanet, OMIM, HPO, ClinVar, and structure-based analysis.

KEY PRINCIPLES:

Report-first - Create report file FIRST, update progressively
Phenotype-driven - Convert symptoms to HPO terms before searching
Multi-database triangulation - Cross-reference Orphanet, OMIM, OpenTargets
Evidence grading - Grade diagnoses by supporting evidence strength
English-first queries - Always use English terms in tool calls

LOOK UP, DON'T GUESS

When uncertain about any scientific fact, SEARCH databases first rather than reasoning from memory.

Tool	WRONG	CORRECT
`OpenTargets_get_associated_drugs_by_target_ensemblID`	`ensemblID`	`ensemblId`
`ClinVar_get_variant_details`	`variant_id`	`id`
`MyGene_query_genes`	`gene`	`q`
`gnomad_get_variant`	`variant`	`variant_id`

Tier	Criteria
T1 (High)	Phenotype match >80% + gene match
T2 (Medium-High)	Phenotype match 60-80% OR likely pathogenic variant
T3 (Medium)	Phenotype match 40-60% OR VUS in candidate gene
T4 (Low)	Phenotype <40% OR uncertain gene

Primary	Fallback 1	Fallback 2
`get_joint_associated_diseases_by_HPO_ID_list`	`Orphanet_search_diseases`	PubMed phenotype search
`ClinVar_get_variant_details`	`gnomad_get_variant`	VEP annotation
`GTEx_get_expression_summary`	`HPA_search_genes_by_query`	Tissue-specific literature

Tooluniverse Rare Disease Diagnosis

Rare Disease Diagnosis Advisor

LOOK UP, DON'T GUESS

COMPUTE, DON'T DESCRIBE

Tooluniverse Rare Disease Diagnosis

Rare Disease Diagnosis Advisor

LOOK UP, DON'T GUESS

COMPUTE, DON'T DESCRIBE

Clinical Reasoning Framework (BEFORE Tools)

Tool Parameter Corrections

Workflow

Key Phase Details

Evidence Grading

Fallback Chains

Reference Files

Healthcare Cdss Patterns

Drug Discovery

Qmd

Attack Tree Construction

Azure Ai Anomalydetector Java

Viboscope