refua-schema 0.7.3

Portfolio-to-drug object schema for the Refua drug discovery ecosystem.

refua-schema

refua-schema is a portfolio-centric object model for the Refua ecosystem. It starts with Portfolio, nests Disease, then Rationale, then Drug, and reuses canonical scientific and workflow objects from sibling Refua packages instead of redefining parallel versions.

What it provides

• A top-level object hierarchy for discovery portfolios: Portfolio -> Disease -> Rationale -> Drug.
• Reuse of core refua entities such as Protein, SmallMolecule, Binder, Complex, DNA, and RNA.
• Reuse of downstream workflow objects from:
  • refua-clinical for SimulationConfig and TrialSimulationResult
  • refua-preclinical for PreclinicalStudySpec
  • refua-regulatory for bundle and provenance records
• Domain metadata objects that fit drug discovery naturally: Evidence, Biomarker, Assay, Modality, AdmetProfile, and ClinicalTrial.
• JSON/YAML round-tripping for portfolios that preserve nested Refua object types.

Install

cd refua-schema
pip install -e .

With development tooling:

poetry install -E dev

With optional SQLModel persistence support:

poetry install -E sqlmodel

With both:

poetry install -E dev -E sqlmodel

Quickstart

from pathlib import Path

from refua import Complex, Protein, SmallMolecule
from refua_clinical.models import default_simulation_config
from refua_preclinical.models import default_study_spec
from refua_schema import (
    AdmetProfile,
    Assay,
    Disease,
    Drug,
    Modality,
    Portfolio,
    Rationale,
)

egfr = Protein(sequence="LEEKKGNYVVTDHAFV...", ids="A")
lead = SmallMolecule.from_smiles("CCOc1ccc(NC(=O)N2CCN(C)CC2)cc1", name="lead-1")
binding_model = Complex([egfr, lead], name="egfr-lead-1")

trial = default_simulation_config()
trial.trial_id = "egfr-phase2"
trial.indication = "Non-small cell lung cancer"

tox = default_study_spec()
tox.study_id = "egfr-28d-tox"
tox.indication = "Oncology"

portfolio = Portfolio(portfolio_id="solid-tumors", name="Solid Tumor Portfolio")
portfolio.add_disease(
    Disease(
        disease_id="nsclc",
        name="Non-small cell lung cancer",
        rationales=[
            Rationale(
                rationale_id="egfr-driver",
                title="EGFR oncogenic signaling",
                hypothesis="EGFR-driven tumors remain vulnerable to selective kinase blockade.",
                proteins=[egfr],
                refua_objects=[binding_model],
                drugs=[
                    Drug(
                        drug_id="lead-1",
                        name="Lead 1",
                        modality=Modality(name="oral small molecule", kind="small_molecule", route="oral"),
                        mechanism_of_action="Selective EGFR inhibition",
                        structures=[lead],
                        admet_profiles=[
                            AdmetProfile(
                                profile_id="lead-1-admet",
                                source="txgemma",
                                smiles="CCOc1ccc(NC(=O)N2CCN(C)CC2)cc1",
                                summary_scores={"admet_score": 0.72, "safety_score": 0.68},
                                endpoint_scores={"score_hERG": 0.61, "score_DILI": 0.70},
                            )
                        ],
                        assays=[
                            Assay(
                                assay_id="egfr-biochem",
                                name="EGFR biochemical potency",
                                assay_type="biochemical",
                                endpoint="IC50",
                                result_value=14.2,
                                unit="nM",
                            )
                        ],
                        preclinical_studies=[tox],
                        clinical_trials=[],
                    )
                ],
            )
        ],
    )
)

portfolio.save(Path("artifacts/portfolio.yaml"))
round_tripped = Portfolio.load(Path("artifacts/portfolio.yaml"))
assert round_tripped.diseases[0].rationales[0].drugs[0].name == "Lead 1"

SQLModel persistence

refua-schema includes an optional SQLModel adapter in refua_schema.sqlmodel_support. It is intentionally thin:

• The canonical source of truth remains the Portfolio Pydantic model.
• SQL storage keeps one full serialized portfolio payload.
• Lightweight index tables for diseases, rationales, and drugs make the hierarchy queryable without reproducing the entire schema as ORM columns.

Example:

from pathlib import Path

from refua_schema import Disease, Drug, Portfolio, Rationale
from refua_schema.sqlmodel_support import PortfolioStore

portfolio = Portfolio(
    portfolio_id="pf-sql",
    name="SQL Portfolio",
    diseases=[
        Disease(
            disease_id="dis-sql",
            name="SQL Disease",
            rationales=[
                Rationale(
                    rationale_id="rat-sql",
                    title="SQL Rationale",
                    hypothesis="Persist canonical portfolio payloads with a thin relational index.",
                    drugs=[
                        Drug.from_smiles(
                            drug_id="drug-sql",
                            name="SQL Drug",
                            smiles="CCO",
                        )
                    ],
                )
            ],
        )
    ],
)

store = PortfolioStore.sqlite(Path("artifacts/portfolio.sqlite"))
store.create_schema()
store.save(portfolio)

reloaded = store.load("pf-sql")
assert reloaded.to_dict() == portfolio.to_dict()
assert len(store.list_drugs(portfolio_id="pf-sql")) == 1

Validation

• All core schema models use Pydantic validation with field descriptions.
• Assignment validation stays enabled after object creation.
• The package round-trips JSON/YAML payloads while preserving canonical nested Refua object types where supported by the serializer.

Release checks

Typical first-release verification flow:

poetry check
poetry install -E dev -E sqlmodel
poetry run ruff check src tests
poetry run pytest
poetry build

Design notes

• Protein, SmallMolecule, and other structural entities stay in refua.
• Clinical simulation config/results stay in refua-clinical.
• Preclinical study specs stay in refua-preclinical.
• Audit and provenance records stay in refua-regulatory.
• refua-schema owns the portfolio-level composition layer that links them together.
• Optional SQL persistence stays in refua_schema.sqlmodel_support so the core schema does not take a hard dependency on SQLModel.