rare-os DomainOS¶

Status: Graduated (production, ADR-009)
Engine: rare-os
Domain: Rare disease / Mendelian (ACMG, de novo, exome diagnosis)

Rare-disease DomainOS: ACMG classification, de novo / compound-het calling, Mendelian trio analysis, and exome diagnosis. Graduated 2026-04-12 (ADR-009) with ~15 skills and 887 passing tests.

Field	Value
Product	rare-os
Engine id	`rare-os`
Intent key	`rare_os`
Repository	`Hordago-Labs/rare-os`
Plugin	`rare-os`
Maturity (registry)	Graduated (production, ADR-009)

Overview¶

Rare-disease DomainOS: ACMG classification, de novo / compound-het calling, Mendelian trio analysis, and exome diagnosis. Graduated 2026-04-12 (ADR-009) with ~15 skills and 887 passing tests.

Scientific approach¶

rare-os structures every run as 5 phases. Gates marked HITL require an explicit human-in-the-loop approval before the run advances.

#	Phase	Gate	HITL
1	Trio Assembly	Assemble proband and parental samples.	No
2	Variant Calling	Call and joint-genotype exome variants.	No
3	Inheritance Filtering	Filter de novo / compound-het / recessive.	No
4	ACMG Classification	Classify variants per ACMG criteria.	No
5	Diagnostic Report	Approve the diagnostic interpretation.	Yes

Capabilities & evidence objects¶

Domain tools / skills

acmg-classifier
de-novo-caller
compound-het
trio-analysis

Evidence objects

Object	Role	Consumer
`result.json`	produces	co-writer
`provenance.json`	produces	evidence-audit

Canonical artifacts (5-artifact contract)

Planned

The 5-artifact contract below is the target shape. Canonical-artifact emission is tracked as inherited debt (Wave 3C) and is not yet guaranteed.

Artifact	Description
`result.json`	Structured primary result payload for the domain run.
`report.md`	Human-readable narrative summary of the analysis.
`provenance.json`	Tool versions, reference data, and algorithm lineage for reproducibility.
`gate_status.json`	Per-phase gate pass/fail decisions.
`session_summary.json`	Session metadata for replay and audit.

Standalone quickstart¶

Zero platform dependency

This quickstart runs the DomainOS standalone. The Hordago platform is not required; platform composition is opt-in (see Composition below).

Install the standalone rare-os plugin (Hordago-Labs/rare-os) -- no Hordago platform required.
Invoke the domain skill with a rare-os intent (see the intent keywords below).
Review the emitted artifacts under the run's output directory.

Intent keywords (route to this engine):

rare disease \bacmg\b de novo variant compound het mendelian rare variant diagnostic odyssey exome diagnosis

Worked example¶

Exome trio diagnosis with ACMG classification

A user submits a proband-parents exome trio for a diagnostic odyssey. rare-os calls variants, filters by inheritance model, classifies candidates against ACMG criteria, and drafts a diagnostic report for sign-off.

Validation & benchmarks¶

Benchmarks

ACMG classification concordance
De novo precision/recall

Reproducibility. provenance.json pins transcript set and ACMG rule versions.

Reference¶

MCP fallback servers (used when the plugin is unavailable): pubmed, open-targets, clinical-trials

Source documents

Scaffold-domains ledger (rare-os): references/scaffold-domains.md

Composition¶

Platform opt-in

rare-os runs standalone. When composed under the Hordago platform it gains cross-domain routing, the Shared Compiler gate, and evidence-audit provenance enforcement. Platform composition is opt-in; the quickstart above has zero platform dependency.

Cross-domain dependencies

Engine	Relationship
`clinical-os`	Diagnostic findings can feed EHR / clinical-trials context.