@inflexa-ai/harness 0.35.7 → 0.36.0

package/dist/workflows/target-assessment/assemblers/safety.d.ts

@@ -1,374 +0,0 @@
-/**
- * Phase-4 deterministic assemblers — safety sections.
- *
- * Each assembler maps Phase-1 / Phase-2 / Phase-3 outputs onto the
- * corresponding dossier section schema. Coverage is honored end-to-end:
- * when an upstream came back `queried_no_data` or the derived row set is
- * empty, the section is marked `queried_no_data` / `not_loaded` rather
- * than fabricated. Aggregate rows preserve their contributing evidence
- * under `evidence: [...]` arrays.
- */
-import type { ClaimSupport, EvidenceItem, RegulatoryActionRow, RegulatoryOrganSignals } from "@inflexa-ai/harness/contracts/target-dossier.js";
-import { type OrganSignalProjection } from "../lib/fda-label-safety.js";
-import { type OrganSystem } from "../../../contracts/organ-system.js";
-import type { Phase2Bundle } from "../steps/phase2-aggregate.js";
-import type { Phase3Bundle } from "../steps/phase3-aggregate.js";
-import type { FamilyComplexesBundle } from "../schemas.js";
-import { HIGH_EXPRESSION_TPM_THRESHOLD } from "../lib/expression-constants.js";
-export { HIGH_EXPRESSION_TPM_THRESHOLD };
-import type { ChemblModulator } from "../../../tools/lib/chembl-client.js";
-export declare const SAFETY_RELEVANT_ORGANS: Set<string>;
-/**
- * Resolve a tissue (and its atlas organ label, when present) onto the
- * canonical organ vocabulary. Returns null when the anatomy has no organ
- * system to belong to — the caller drops the row rather than filing it
- * under a neighbouring organ.
- */
-export declare function resolveTissueOrganSystem(tissue: string, organ?: string | null): OrganSystem | null;
-export declare function isSafetyRelevant(tissue: string, organ?: string | null): boolean;
-export declare const REPRODUCTIVE_TOX_TISSUES: Set<string>;
-export declare const REPRODUCTIVE_TOX_TPM_FLOOR = 20;
-export declare const DEFAULT_TPM_FLOOR = 100;
-export declare function meetsTpmFloor(tissue: string, value: number): boolean;
-export declare function assembleLiabilitySummary(phase2: Phase2Bundle, context: {
-    offTargetRows: OffTargetPanelRows | null;
-    preferredModality: string | null;
-}): {
-    liability_bullets: never[];
-    modality_recommendation: string | null;
-    same_class_drug_count: number;
-    inferred_therapeutic_area: string | null;
-    no_liabilities_disclosure: string;
-};
-type FanoutResults = Phase3Bundle["fanout"];
-export declare function aggregateFaersAcrossModulators(fanout: FanoutResults | undefined): {
-    total_reports: number;
-    seriousness: {
-        coverage: "available";
-        total_reports: number;
-        by_seriousness: {
-            death: number;
-            life_threatening: number;
-            hospitalization: number;
-            disabling: number;
-            other_serious: number;
-            congenital_anomaly: number;
-        };
-        fatal_report_count: number;
-    } | {
-        coverage: "queried_no_data";
-        total_reports: number;
-        by_seriousness?: undefined;
-        fatal_report_count?: undefined;
-    };
-    top_signals: {
-        meddra_term: string;
-        organ: "hematologic" | "metabolic" | "immune" | "hepatic" | "musculoskeletal" | "cns" | "renal" | "reproductive" | "respiratory" | "cardiac" | "vascular" | "pns" | "gi" | "pancreas" | "endocrine_thyroid" | "dermatologic" | "ocular" | "oncology" | undefined;
-        report_count: number;
-    }[];
-    per_modulator: {
-        modulator: string;
-        modulator_id: string | null;
-        report_count: number;
-        coverage: "available" | "queried_no_data" | "not_loaded";
-    }[];
-} | null;
-export declare function aggregateTrialAes(fanout: FanoutResults | undefined): {
-    serious: {
-        term: string;
-        incidence_pct: number;
-        organ?: string;
-        nct_ids: string[];
-    }[];
-    non_serious: {
-        term: string;
-        incidence_pct: number;
-        organ?: string;
-        nct_ids: string[];
-    }[];
-    non_serious_floor_pct: number;
-    dropped_uninformative_count: number;
-    coverage_qualifier: {
-        trials_queried: number;
-        trials_with_ae_data: number;
-        serious_floor_applied: number;
-        non_serious_floor_pct_applied: number;
-    };
-} | null;
-/** Fold below this threshold → selectivity window is insufficient. */
-export declare const SELECTIVITY_FOLD_THRESHOLD = 30;
-export type RawOffTargetRow = {
-    off_target_id?: string | null;
-    off_target_name?: string | null;
-    target_chembl_id?: string | null;
-    target_type?: string | null;
-    accession?: string | null;
-    pchembl: number;
-    selectivity: {
-        fold: number;
-        log_units: number;
-    };
-    selectivity_window_below_threshold?: boolean;
-    evidence?: EvidenceItem[];
-    organ_system?: OrganSystem | null;
-    target_class?: string | undefined;
-    is_safety_panel_target?: boolean;
-    clinical_consequence?: string | null;
-    metadata?: {
-        merged_chembl_ids?: string[];
-    };
-};
-export type CleanOffTargetRow = Omit<RawOffTargetRow, "target_chembl_id" | "target_type" | "accession" | "off_target_id" | "organ_system" | "evidence"> & {
-    off_target_id: string | null;
-    off_target_name: string;
-    organ_system: OrganSystem | null;
-    evidence: EvidenceItem[];
-    selectivity_window_below_threshold: boolean;
-    clinical_consequence: string | null;
-    is_safety_panel_target: boolean;
-    metadata: {
-        merged_chembl_ids: string[];
-    };
-};
-/**
- * Off-target row shape after relationship classification. Used by the
- * organ-rollup builder, evidence tally, and liability-summary signal count —
- * the typed members all rely on `relationship`, `organ_system`, `pchembl`,
- * `support`, and `is_safety_panel_target` only.
- */
-export type OffTargetPanelRows = Array<{
-    off_target_id: string | null;
-    off_target_name: string;
-    pchembl: number;
-    is_safety_panel_target: boolean;
-    organ_system: OrganSystem | null;
-    support: ClaimSupport;
-    relationship: "off_target";
-}>;
-/**
- * Partition evidence into what a claim can stand on: an item resolves to a
- * record a reader can check, or it does not. A claim with nothing checkable
- * says so rather than presenting provenance labels as citations.
- */
-export declare function claimSupportFrom(evidence: EvidenceItem[], reasonWhenUnsupported: string): ClaimSupport;
-/** The evidence behind a claim, or nothing when the claim states it has none. */
-export declare function claimSupportEvidence(support: ClaimSupport): EvidenceItem[];
-/**
- * Turn segmented FDA label warnings into the dossier's per-organ regulatory
- * signal section.
- *
- * The organ-resolution filter can legitimately empty this section: a set of
- * labels whose every warning fragment names no canonical organ produces no
- * rows. That is `filtered` with the count it discarded, never an `available`
- * section with an empty list — the difference is whether a reader learns that
- * signals existed and did not survive attribution.
- */
-export declare function assembleRegulatoryOrganSignals(projection: OrganSignalProjection | null): RegulatoryOrganSignals;
-/**
- * Filter and deduplicate raw off-target rows before panel assembly.
- *
- * Removes: on-target self-rows, cell-line entries, sentinel/unresolved names.
- * Deduplicates: by UniProt accession when present, otherwise by normalized name;
- *   keeps the highest-pchembl row as the winner and records merged ChEMBL ids.
- * Computes: `selectivity_window_below_threshold`, `clinical_consequence`,
- *   `is_safety_panel_target` (via the existing safety-panel lookup).
- */
-export declare function filterAndDedupOffTargetRows(rows: RawOffTargetRow[], ctx: {
-    assessmentTargetChemblId: string | null;
-}): CleanOffTargetRow[];
-/**
- * Off-target panel row split. Each clean off-target row is classified as:
- *   - `on_target_self_hit`: alternate ChEMBL ID for the assessment target itself
- *   - `intended_co_target`: every modulator that hits this target intends it
- *     (e.g., GLP1R + GIPR for tirzepatide); not an off-target liability
- *   - `off_target`: real off-target — selectivity computed vs primary potency
- */
-export declare function aggregateOffTargetPanel(phase2: Phase2Bundle, fanout: FanoutResults | undefined, assessmentUniprot: string, assessmentGeneSymbol?: string, familyComplexes?: FamilyComplexesBundle | null, onTargetChemblIds?: string[]): {
-    rows: {
-        off_target_id: string | null;
-        off_target_name: string;
-        pchembl: number;
-        is_safety_panel_target: boolean;
-        organ_system: "hematologic" | "metabolic" | "immune" | "hepatic" | "musculoskeletal" | "cns" | "renal" | "reproductive" | "respiratory" | "cardiac" | "vascular" | "pns" | "gi" | "pancreas" | "endocrine_thyroid" | "dermatologic" | "ocular" | "oncology" | null;
-        clinical_consequence: string | null;
-        selectivity: {
-            vs_primary_potency: {
-                primary_pchembl_used: number;
-                primary_source: "chembl_target_drug_indication" | "literature_curated";
-                fold: number;
-                log_units: number;
-            };
-        } | {
-            selectivity_unknown: true;
-            reason: string;
-        };
-        selectivity_window_below_threshold: boolean;
-        relationship: "off_target";
-        support: {
-            state: "scored";
-            evidence: {
-                source: string;
-                pmid?: string | undefined;
-                doi?: string | undefined;
-                accession?: string | undefined;
-                predicate?: string | undefined;
-                score?: number | undefined;
-                strength?: string | undefined;
-                is_human?: boolean | undefined;
-                is_clinical?: boolean | undefined;
-                excerpt?: string | undefined;
-                metadata?: Record<string, unknown> | undefined;
-                regulatory_reference?: {
-                    document: string;
-                    section?: string | undefined;
-                    doc_id?: string | undefined;
-                    doc_url?: string | undefined;
-                } | undefined;
-            }[];
-        } | {
-            state: "unknown";
-            reason: string;
-        };
-        target_class?: string | undefined;
-        metadata?: {
-            merged_chembl_ids?: string[] | undefined;
-        } | undefined;
-    }[];
-    excluded_rows: {
-        off_target_id: string | null;
-        off_target_name: string;
-        pchembl: number;
-        is_safety_panel_target: boolean;
-        organ_system: "hematologic" | "metabolic" | "immune" | "hepatic" | "musculoskeletal" | "cns" | "renal" | "reproductive" | "respiratory" | "cardiac" | "vascular" | "pns" | "gi" | "pancreas" | "endocrine_thyroid" | "dermatologic" | "ocular" | "oncology" | null;
-        clinical_consequence: string | null;
-        selectivity: {
-            vs_primary_potency: {
-                primary_pchembl_used: number;
-                primary_source: "chembl_target_drug_indication" | "literature_curated";
-                fold: number;
-                log_units: number;
-            };
-        } | {
-            selectivity_unknown: true;
-            reason: string;
-        };
-        selectivity_window_below_threshold: boolean;
-        relationship: "intended_co_target" | "on_target_self_hit" | "obligate_cofactor";
-        reason: string;
-        evidence: {
-            source: string;
-            pmid?: string | undefined;
-            doi?: string | undefined;
-            accession?: string | undefined;
-            predicate?: string | undefined;
-            score?: number | undefined;
-            strength?: string | undefined;
-            is_human?: boolean | undefined;
-            is_clinical?: boolean | undefined;
-            excerpt?: string | undefined;
-            metadata?: Record<string, unknown> | undefined;
-            regulatory_reference?: {
-                document: string;
-                section?: string | undefined;
-                doc_id?: string | undefined;
-                doc_url?: string | undefined;
-            } | undefined;
-        }[];
-        target_class?: string | undefined;
-        metadata?: {
-            merged_chembl_ids?: string[] | undefined;
-        } | undefined;
-    }[];
-} | null;
-/** Minimum distinct active substances required for class-liability designation. */
-export declare const CLASS_MIN_DRUGS = 3;
-export declare const CLASS_LIABILITY_FRACTION = 0.3;
-export type ClassDrug = {
-    drug_id: string;
-    parent_chembl_id: string | null;
-    drug_name: string;
-    max_phase: number;
-};
-/**
- * Deduplicates a list of drugs by active substance (parent_chembl_id, falling
- * back to drug_id when parent is absent), then derives the count and suppression
- * reason used consistently across drugs_in_class and per_organ rollups.
- *
- * Dedup winner per group: highest max_phase; ties broken by drug_id lexicographic
- * order so the result is deterministic.
- */
-export declare function computeClassPrecedentCounts(drugs: ClassDrug[]): {
-    drug_count_in_class: number;
-    drugs_in_class: ClassDrug[];
-    suppressed_reason: string | null;
-};
-export declare function aggregateClassPrecedent(phase2: Phase2Bundle, fanout: FanoutResults | undefined): {
-    drugs_in_class: ClassDrug[];
-    per_organ: {
-        organ: "hematologic" | "metabolic" | "immune" | "hepatic" | "musculoskeletal" | "cns" | "renal" | "reproductive" | "respiratory" | "cardiac" | "vascular" | "pns" | "gi" | "pancreas" | "endocrine_thyroid" | "dermatologic" | "ocular" | "oncology";
-        drug_count_in_class: number;
-        drugs_with_signal: number;
-        signal_fraction: number;
-        is_class_liability: boolean;
-        suppressed_reason: string | null;
-        top_aes: {
-            term: string;
-            report_count: number;
-        }[];
-    }[];
-} | null;
-export declare function buildOrganRollup(faers: ReturnType<typeof aggregateFaersAcrossModulators>, trialAes: ReturnType<typeof aggregateTrialAes>, offTarget: OffTargetPanelRows | null, classP: ReturnType<typeof aggregateClassPrecedent>, regulatoryActions?: RegulatoryActionRow[] | null): {
-    organ: "hematologic" | "metabolic" | "immune" | "hepatic" | "musculoskeletal" | "cns" | "renal" | "reproductive" | "respiratory" | "cardiac" | "vascular" | "pns" | "gi" | "pancreas" | "endocrine_thyroid" | "dermatologic" | "ocular" | "oncology";
-    risk_level: "low" | "medium" | "high";
-    signal_type_count: number;
-    signals: {
-        chembl_polypharm_count: number;
-        faers_count: number;
-        trial_ae_count: number;
-        class_liability_present: boolean;
-    };
-    evidence: {
-        source: string;
-        pmid?: string | undefined;
-        doi?: string | undefined;
-        accession?: string | undefined;
-        predicate?: string | undefined;
-        score?: number | undefined;
-        strength?: string | undefined;
-        is_human?: boolean | undefined;
-        is_clinical?: boolean | undefined;
-        excerpt?: string | undefined;
-        metadata?: Record<string, unknown> | undefined;
-        regulatory_reference?: {
-            document: string;
-            section?: string | undefined;
-            doc_id?: string | undefined;
-            doc_url?: string | undefined;
-        } | undefined;
-    }[];
-}[] | null;
-export declare function assembleDrugInteractions(phase2: Phase2Bundle, enrichedModulators?: ChemblModulator[]): {
-    drug_id: string;
-    drug_name: string;
-    best_score: number;
-    predicates: string[];
-    sources: string[];
-    paper_count: number;
-    dominant_direction: "unknown";
-    has_human_evidence: boolean;
-    has_clinical_evidence: boolean;
-    evidence: {
-        source: string;
-        predicate: string;
-        score: number;
-        is_clinical: boolean;
-        is_human: boolean;
-        metadata: {
-            chembl_id: string;
-            max_phase: number;
-            molecule_type: string | null;
-            first_approval: number | null;
-            triage_rationale: string | undefined;
-        };
-    }[];
-}[] | null;