tooluniverse-rare-disease-diagnosis

name	tooluniverse-rare-disease-diagnosis
description	Rare disease differential diagnosis from patient phenotype — HPO term matching to candidate diseases (Orphanet, OMIM), gene panel prioritization, ACMG variant interpretation, and structure-based variant analysis. Use for diagnostic odyssey assistance, phenotype-to-disease ranking, and genetic-counseling differential generation.

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:

1. Report-first - Create report file FIRST, update progressively
2. Phenotype-driven - Convert symptoms to HPO terms before searching
3. Multi-database triangulation - Cross-reference Orphanet, OMIM, OpenTargets
4. Evidence grading - Grade diagnoses by supporting evidence strength
5. 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.

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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.

Clinical Reasoning Framework (BEFORE Tools)

Apply these strategies to form a 3-5 candidate differential, then use tools to confirm/refute:

1. Multi-system involvement - Symptoms spanning 2+ organ systems = strongest rare disease signal. Ask: what single pathway explains ALL features?
2. Regression question - Losing abilities vs never acquired? Regression = neurodegenerative/metabolic storage. Stable = developmental/structural.