@inflexa-ai/harness 0.17.0 → 0.18.0

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

@@ -8,15 +8,23 @@
  * than fabricated. Aggregate rows preserve their contributing evidence
  * under `evidence: [...]` arrays.
  */
-import type { EvidenceItem, RegulatoryActionRow } from "@inflexa-ai/harness/contracts/target-dossier.js";
+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 { type CanonicalOrgan } from "../lib/meddra-organ-map.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;
@@ -55,7 +63,7 @@ export declare function aggregateFaersAcrossModulators(fanout: FanoutResults | u
     };
     top_signals: {
         meddra_term: string;
-        organ: CanonicalOrgan | undefined;
+        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: {
@@ -102,7 +110,7 @@ export type RawOffTargetRow = {
     };
     selectivity_window_below_threshold?: boolean;
     evidence?: EvidenceItem[];
-    organ_system?: string | null;
+    organ_system?: OrganSystem | null;
     target_class?: string | undefined;
     is_safety_panel_target?: boolean;
     clinical_consequence?: string | null;
@@ -113,7 +121,7 @@ export type RawOffTargetRow = {
 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: string | null;
+    organ_system: OrganSystem | null;
     evidence: EvidenceItem[];
     selectivity_window_below_threshold: boolean;
     clinical_consequence: string | null;
@@ -123,20 +131,39 @@ export type CleanOffTargetRow = Omit<RawOffTargetRow, "target_chembl_id" | "targ
     };
 };
 /**
- * V4 off-target row shape after relationship classification. Used by the
+ * 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`,
- * `evidence`, and `is_safety_panel_target` only.
+ * `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: string | null;
-    evidence: EvidenceItem[];
+    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.
  *
@@ -150,7 +177,7 @@ export declare function filterAndDedupOffTargetRows(rows: RawOffTargetRow[], ctx
     assessmentTargetChemblId: string | null;
 }): CleanOffTargetRow[];
 /**
- * V4 off-target panel row split. Each clean off-target row is classified as:
+ * 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
@@ -162,7 +189,7 @@ export declare function aggregateOffTargetPanel(phase2: Phase2Bundle, fanout: Fa
         off_target_name: string;
         pchembl: number;
         is_safety_panel_target: boolean;
-        organ_system: string | null;
+        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: {
@@ -176,25 +203,32 @@ export declare function aggregateOffTargetPanel(phase2: Phase2Bundle, fanout: Fa
             reason: string;
         };
         selectivity_window_below_threshold: boolean;
-        evidence: {
-            source: string;
-            pmid?: string | undefined;
-            doi?: 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;
-        }[];
         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;
@@ -205,7 +239,7 @@ export declare function aggregateOffTargetPanel(phase2: Phase2Bundle, fanout: Fa
         off_target_name: string;
         pchembl: number;
         is_safety_panel_target: boolean;
-        organ_system: string | null;
+        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: {
@@ -219,10 +253,13 @@ export declare function aggregateOffTargetPanel(phase2: Phase2Bundle, fanout: Fa
             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;
@@ -237,8 +274,6 @@ export declare function aggregateOffTargetPanel(phase2: Phase2Bundle, fanout: Fa
                 doc_url?: string | undefined;
             } | undefined;
         }[];
-        relationship: "intended_co_target" | "on_target_self_hit" | "obligate_cofactor";
-        reason: string;
         target_class?: string | undefined;
         metadata?: {
             merged_chembl_ids?: string[] | undefined;
@@ -270,7 +305,7 @@ export declare function computeClassPrecedentCounts(drugs: ClassDrug[]): {
 export declare function aggregateClassPrecedent(phase2: Phase2Bundle, fanout: FanoutResults | undefined): {
     drugs_in_class: ClassDrug[];
     per_organ: {
-        organ: CanonicalOrgan;
+        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;
@@ -283,7 +318,7 @@ export declare function aggregateClassPrecedent(phase2: Phase2Bundle, fanout: Fa
     }[];
 } | null;
 export declare function buildOrganRollup(faers: ReturnType<typeof aggregateFaersAcrossModulators>, trialAes: ReturnType<typeof aggregateTrialAes>, offTarget: OffTargetPanelRows | null, classP: ReturnType<typeof aggregateClassPrecedent>, regulatoryActions?: RegulatoryActionRow[] | null): {
-    organ: CanonicalOrgan;
+    organ: "hematologic" | "metabolic" | "immune" | "hepatic" | "musculoskeletal" | "cns" | "renal" | "reproductive" | "respiratory" | "cardiac" | "vascular" | "pns" | "gi" | "pancreas" | "endocrine_thyroid" | "dermatologic" | "ocular" | "oncology";
     risk_level: "high" | "medium" | "low";
     signal_type_count: number;
     signals: {
@@ -296,6 +331,7 @@ export declare function buildOrganRollup(faers: ReturnType<typeof aggregateFaers
         source: string;
         pmid?: string | undefined;
         doi?: string | undefined;
+        accession?: string | undefined;
         predicate?: string | undefined;
         score?: number | undefined;
         strength?: string | undefined;
@@ -311,20 +347,6 @@ export declare function buildOrganRollup(faers: ReturnType<typeof aggregateFaers
         } | undefined;
     }[];
 }[] | null;
-/**
- * Testable wrapper around `buildOrganRollup` that accepts named parameters.
- * Exported for unit tests; production code calls `buildOrganRollup` directly
- * inside `assembleDossier`.
- */
-export declare function assembleOrganRollupRows(opts: {
-    classPrecedent?: ReturnType<typeof aggregateClassPrecedent> | null;
-    regulatoryActions?: {
-        coverage: string;
-        data?: {
-            rows: RegulatoryActionRow[];
-        };
-    } | null;
-}): ReturnType<typeof buildOrganRollup> extends null ? never[] : NonNullable<ReturnType<typeof buildOrganRollup>>;
 export declare function assembleDrugInteractions(phase2: Phase2Bundle, enrichedModulators?: ChemblModulator[]): {
     drug_id: string;
     drug_name: string;

package/dist/workflows/target-assessment/assemblers/safety.js

@@ -8,6 +8,8 @@
  * than fabricated. Aggregate rows preserve their contributing evidence
  * under `evidence: [...]` arrays.
  */
+import { ORGAN_RESOLUTION_FILTER } from "../lib/fda-label-safety.js";
+import { ORGAN_SYSTEMS } from "../../../contracts/organ-system.js";
 import { expectedOrgansFromBody } from "../lib/compute-derived.js";
 import { inferTherapeuticArea } from "../../../tools/lib/clinical-benchmarks-client.js";
 import { SafetyPanelFileSchema } from "../../../data/safety-panel-schema.js";
@@ -17,7 +19,7 @@ import { isIntendedCoTarget } from "../lib/intended-polypharm-filter.js";
 import { makeHeterodimerOfAssessmentFilter } from "../lib/heterodimer-filter.js";
 import { buildFamilyComplexSupplement } from "../lib/family-complex-supplement.js";
 import { computeSelectivity } from "../lib/compute-selectivity.js";
-import { classifyOrgan, classifyPolypharmOrgan, classifyTrialAe } from "../lib/meddra-organ-map.js";
+import { classifyOrgan, classifyTrialAe } from "../lib/meddra-organ-map.js";
 import { HIGH_EXPRESSION_TPM_THRESHOLD, CNS_REGION_TPM_FLOOR, MUSCULOSKELETAL_TPM_FLOOR } from "../lib/expression-constants.js";
 export { HIGH_EXPRESSION_TPM_THRESHOLD };
 // ── Safety panel lookup ─────────────────────────────────────────────
@@ -71,6 +73,54 @@ export const SAFETY_RELEVANT_ORGANS = new Set([
     "femur",
     "vertebra",
 ]);
+/**
+ * Anatomical tissue and organ labels from the expression atlases onto the
+ * canonical organ vocabulary. Longest keys first so "bone marrow" is read as
+ * haematopoietic tissue rather than as skeleton.
+ */
+const TISSUE_ORGAN_SYSTEMS = [
+    ["bone marrow", "hematologic"],
+    ["lymph node", "immune"],
+    ["seminal vesicle", "reproductive"],
+    ["fallopian tube", "reproductive"],
+    ["endometrium", "reproductive"],
+    ["epididymis", "reproductive"],
+    ["placenta", "reproductive"],
+    ["prostate", "reproductive"],
+    ["intestine", "gi"],
+    ["vertebra", "musculoskeletal"],
+    ["stomach", "gi"],
+    ["thyroid", "endocrine_thyroid"],
+    ["pancreas", "pancreas"],
+    ["spleen", "immune"],
+    ["retina", "ocular"],
+    ["kidney", "renal"],
+    ["uterus", "reproductive"],
+    ["testis", "reproductive"],
+    ["gonad", "reproductive"],
+    ["ovary", "reproductive"],
+    ["heart", "cardiac"],
+    ["liver", "hepatic"],
+    ["brain", "cns"],
+    ["femur", "musculoskeletal"],
+    ["tibia", "musculoskeletal"],
+    ["lung", "respiratory"],
+    ["bone", "musculoskeletal"],
+];
+/**
+ * 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 function resolveTissueOrganSystem(tissue, organ) {
+    const haystack = `${tissue} ${organ ?? ""}`.toLowerCase();
+    for (const [label, system] of TISSUE_ORGAN_SYSTEMS) {
+        if (haystack.includes(label))
+            return system;
+    }
+    return null;
+}
 export function isSafetyRelevant(tissue, organ) {
     const t = tissue.toLowerCase();
     const o = (organ ?? "").toLowerCase();
@@ -160,22 +210,6 @@ export function meetsTpmFloor(tissue, value) {
     }
     return value > DEFAULT_TPM_FLOOR;
 }
-const CANONICAL_ORGANS = [
-    "cardiac",
-    "hepatic",
-    "cns",
-    "renal",
-    "gi",
-    "pancreas",
-    "endocrine_thyroid",
-    "metabolic",
-    "hematologic",
-    "immune",
-    "respiratory",
-    "reproductive",
-    "dermatologic",
-    "musculoskeletal",
-];
 // ── Liability summary ───────────────────────────────────────────────
 export function assembleLiabilitySummary(phase2, context) {
     const ot = phase2.phase1.collectors.opentargets;
@@ -381,6 +415,53 @@ const SENTINEL_OFF_TARGET_NAMES = new Set(["unchecked", "unknown", "n/a"]);
  * biological targets. Filtered out before panel assembly.
  */
 const CELL_LINE_NAME_PATTERNS = /\b(hek293|hek-293|cho|hela|3t3|293t|293|jurkat|raw264|raw\s*264|cos-7|cos7|mcf-7|mcf7|pc-3|pc3|lncap|a549|u2os|ht-29|ht29|sk-ov-3|skov3|t47d|mda-mb|nih3t3)\b/i;
+/**
+ * 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 function claimSupportFrom(evidence, reasonWhenUnsupported) {
+    const locatable = evidence.filter((e) => Boolean(e.pmid ?? e.doi ?? e.accession ?? e.regulatory_reference));
+    if (locatable.length === 0)
+        return { state: "unknown", reason: reasonWhenUnsupported };
+    return { state: "scored", evidence: locatable };
+}
+/** The evidence behind a claim, or nothing when the claim states it has none. */
+export function claimSupportEvidence(support) {
+    return support.state === "scored" ? support.evidence : [];
+}
+// ── Per-organ regulatory signals ────────────────────────────────────
+/**
+ * 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 function assembleRegulatoryOrganSignals(projection) {
+    if (projection === null) {
+        return { coverage: "not_loaded", reason: "no indication resolved, so no FDA label was queried" };
+    }
+    const rows = projection.signals.map((s) => ({
+        organ: s.organ,
+        drug_name: s.drug_name,
+        agency: "FDA",
+        application_number: s.application_number,
+        label_section: s.label_section,
+        excerpt: s.excerpt,
+        support: claimSupportFrom([s.evidence], `the ${s.label_section} warning for ${s.drug_name} carries no citable label reference`),
+    }));
+    if (rows.length === 0) {
+        if (projection.dropped_count > 0) {
+            return { coverage: "filtered", filter: ORGAN_RESOLUTION_FILTER, dropped_count: projection.dropped_count };
+        }
+        return { coverage: "queried_no_data", error: { message: "the FDA label query returned no attributable warning prose" } };
+    }
+    return { coverage: "available", data: { rows }, dropped_count: projection.dropped_count };
+}
 /**
  * Filter and deduplicate raw off-target rows before panel assembly.
  *
@@ -444,7 +525,7 @@ export function filterAndDedupOffTargetRows(rows, ctx) {
 }
 // ── Off-target panel assembly ───────────────────────────────────────
 /**
- * V4 off-target panel row split. Each clean off-target row is classified as:
+ * 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
@@ -486,10 +567,10 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
                     name: hit.targetName ?? hit.targetChemblId,
                     pchembl: pch,
                     modulatorPrimaryPchembl: primaryPchemblByModulator.get(item.data.moleculeChemblId) ?? null,
-                    modulators: cur?.modulators ?? new Set(),
+                    assayByModulator: cur?.assayByModulator ?? new Map(),
                 });
             }
-            byTarget.get(hit.targetChemblId).modulators.add(item.data.moleculeChemblId);
+            byTarget.get(hit.targetChemblId).assayByModulator.set(item.data.moleculeChemblId, hit.assayChemblId);
         }
     }
     // Map off-target ChEMBL ID → primaryPchembl of the winner modulator so the
@@ -519,9 +600,15 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
             clinical_consequence: safetyHit?.clinical_consequence ?? null,
             selectivity: { log_units: 0, fold: 1 },
             selectivity_window_below_threshold: false,
-            modulators: [...v.modulators],
-            evidence: [...v.modulators].map((m) => ({
+            modulators: [...v.assayByModulator.keys()],
+            // The locator is the assay the binding was measured in — the
+            // record a reader can open to check the asserted activity. The
+            // off-target's own ChEMBL id names the protein, not the
+            // measurement, so an activity ChEMBL did not attribute to an
+            // assay carries no locator and the claim states it has none.
+            evidence: [...v.assayByModulator].map(([m, assayChemblId]) => ({
                 source: "chembl:polypharm",
+                ...(assayChemblId ? { accession: assayChemblId } : {}),
                 predicate: "binds",
                 score: v.pchembl,
                 metadata: { off_target_id: v.chemblId, modulator: m },
@@ -529,7 +616,7 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
         };
     })
         .filter((r) => r !== null);
-    // Preserve modulator membership across dedup so the v4 relationship
+    // Preserve modulator membership across dedup so the relationship
     // classifier (intended co-target / on-target self-hit) can see which
     // molecules actually hit each off-target.
     const modulatorsByKey = new Map();
@@ -549,7 +636,7 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
         }
         return b.pchembl - a.pchembl;
     });
-    // Helper: project a clean row onto the V4 base shape (no relationship yet).
+    // Helper: project a clean row onto the shared body shape (no relationship yet).
     const toBaseRow = (r) => ({
         off_target_id: r.off_target_id,
         off_target_name: r.off_target_name,
@@ -558,7 +645,6 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
         is_safety_panel_target: r.is_safety_panel_target,
         organ_system: r.organ_system,
         clinical_consequence: r.clinical_consequence,
-        evidence: r.evidence,
         metadata: r.metadata,
     });
     const rows = [];
@@ -573,6 +659,7 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
         if (assessmentGeneSymbol && isHeterodimer(r.off_target_name)) {
             excludedRows.push({
                 ...base,
+                evidence: r.evidence,
                 relationship: "obligate_cofactor",
                 reason: `${r.off_target_name} is ${assessmentGeneSymbol} heterodimerised with a different obligate cofactor; selectivity is not pharmacologically attainable.`,
                 selectivity: { selectivity_unknown: true, reason: "obligate cofactor (same protein, different RAMP/accessory)" },
@@ -584,6 +671,7 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
         if (r.off_target_id && assessmentUniprot && isOnTargetChemblId(r.off_target_id, onTargetChemblIds)) {
             excludedRows.push({
                 ...base,
+                evidence: r.evidence,
                 relationship: "on_target_self_hit",
                 reason: `${r.off_target_id} is an alternate ChEMBL ID for the on-target`,
                 selectivity: { selectivity_unknown: true, reason: "on-target self-hit" },
@@ -597,6 +685,7 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
         if (modulators.length > 0 && intendedHits.length === modulators.length) {
             excludedRows.push({
                 ...base,
+                evidence: r.evidence,
                 relationship: "intended_co_target",
                 reason: intendedHits[0].hit.reason,
                 selectivity: { selectivity_unknown: true, reason: "intended co-target" },
@@ -619,6 +708,7 @@ export function aggregateOffTargetPanel(phase2, fanout, assessmentUniprot, asses
             relationship: "off_target",
             selectivity,
             selectivity_window_below_threshold: below,
+            support: claimSupportFrom(r.evidence, `${r.off_target_name} was surfaced by ChEMBL polypharmacology with no citable binding record`),
         });
     }
     // Append the IUPHAR-driven obligate-cofactor supplement for receptor-
@@ -778,13 +868,15 @@ const MALIGNANCY_RE = /malignan|cancer|carcinoma|neoplasm/i;
 export function buildOrganRollup(faers, trialAes, offTarget, classP, regulatoryActions) {
     if (!faers && !trialAes && !offTarget && !classP && !regulatoryActions?.length)
         return null;
-    const rows = CANONICAL_ORGANS.map((organ) => {
-        // off_target_panel.organ_system is the curated safety-panel canonical
-        // string (`cardiac` | `hepatic` | `cns` | `renal` | `gi` |
-        // `hematologic` | `immune` | `metabolic` | `respiratory`). Use direct
-        // string equality first; `classifyOrgan` falls back if a future
-        // collector emits a non-canonical string.
-        const polypharmHits = (offTarget ?? []).filter((r) => classifyPolypharmOrgan(r.organ_system) === organ);
+    // The rollup walks the canonical vocabulary itself, so the organs it can
+    // emit, the organs `expectedOrgansFromBody` can expect, and the organs a
+    // producer can attribute are one set. A row with no signal is dropped
+    // below, so widening the vocabulary widens the rollup rather than opening
+    // a gap between expected and present organs.
+    const rows = ORGAN_SYSTEMS.map((organ) => {
+        // off_target_panel.organ_system is a canonical token, so the match is
+        // equality on the vocabulary rather than a comparison of prose.
+        const polypharmHits = (offTarget ?? []).filter((r) => r.organ_system === organ);
         const polypharmCount = polypharmHits.length;
         const faersHits = (faers?.top_signals ?? []).filter((s) => s.organ === organ);
         const faersCount = faersHits.length;
@@ -894,7 +986,7 @@ export function buildOrganRollup(faers, trialAes, offTarget, classP, regulatoryA
     }
     // Oncology synthesis: when regulatory_actions carries malignancy-keyword
     // findings, emit an oncology rollup row. This is ADDITIVE — it does not
-    // replace any row produced by the main CANONICAL_ORGANS loop above.
+    // replace any row produced by the vocabulary loop above.
     if (!presentOrgans.has("oncology") && regulatoryActions?.length) {
         const malignancyRows = regulatoryActions.filter((r) => MALIGNANCY_RE.test(r.finding));
         if (malignancyRows.length > 0) {
@@ -923,15 +1015,6 @@ export function buildOrganRollup(faers, trialAes, offTarget, classP, regulatoryA
     }
     return filtered;
 }
-/**
- * Testable wrapper around `buildOrganRollup` that accepts named parameters.
- * Exported for unit tests; production code calls `buildOrganRollup` directly
- * inside `assembleDossier`.
- */
-export function assembleOrganRollupRows(opts) {
-    const regRows = opts.regulatoryActions?.coverage === "available" ? (opts.regulatoryActions.data?.rows ?? null) : null;
-    return buildOrganRollup(null, null, null, opts.classPrecedent ?? null, regRows) ?? [];
-}
 // ── §2.4 Drug Interactions ──────────────────────────────────────────
 export function assembleDrugInteractions(phase2, enrichedModulators) {
     const mods = phase2.phase1.collectors.chemblModulators;

package/dist/workflows/target-assessment/collectors/index.d.ts

@@ -24,7 +24,7 @@ export interface CollectorCtx {
     readonly ncbiApiKey?: string;
 }
 import type { SerializedError } from "../coverage.js";
-import type { CbioportalBundle, ChemblModulatorsBundle, ClinvarBundle, CtgovBundle, ExpressionHumanBundle, ExpressionMultiSpeciesBundle, FaersByTargetBundle, FamilyComplexesBundle, ImpcBundle, OpenTargetsBundle, PathwaysBundle, PubmedIndexBundle, ResolvedTarget, StringPpiBundle, TherapeuticProgramsBundle } from "../schemas.js";
+import type { CbioportalBundle, ChemblModulatorsBundle, ClinvarBundle, CtgovBundle, ExpressionHumanBundle, ExpressionMultiSpeciesBundle, FaersByTargetBundle, FamilyComplexesBundle, ImpcBundle, MonarchBundle, OpenTargetsBundle, PathwaysBundle, PubmedIndexBundle, ResolvedTarget, StringPpiBundle, TherapeuticProgramsBundle } from "../schemas.js";
 type CoverageAvailable<T> = {
     coverage: "available";
     data: T;
@@ -47,6 +47,7 @@ export declare function collectExpressionMultiSpecies(input: ResolvedTarget): Pr
 export declare function collectFaersByTarget(input: ResolvedTarget): Promise<CoverageEnvelope<FaersByTargetBundle>>;
 export declare function collectFamilyComplexes(input: ResolvedTarget): Promise<CoverageEnvelope<FamilyComplexesBundle>>;
 export declare function collectImpc(input: ResolvedTarget): Promise<CoverageEnvelope<ImpcBundle>>;
+export declare function collectMonarch(input: ResolvedTarget): Promise<CoverageEnvelope<MonarchBundle>>;
 export declare function collectOpenTargets(input: ResolvedTarget): Promise<CoverageEnvelope<OpenTargetsBundle>>;
 export declare function collectPathways(input: ResolvedTarget): Promise<CoverageEnvelope<PathwaysBundle>>;
 export declare function collectPubmedIndex(input: ResolvedTarget, ctx: CollectorCtx): Promise<CoverageEnvelope<PubmedIndexBundle>>;
@@ -85,6 +86,9 @@ export declare const COLLECTOR_MANIFEST: readonly [{
 }, {
     readonly id: "impc";
     readonly run: typeof collectImpc;
+}, {
+    readonly id: "monarch";
+    readonly run: typeof collectMonarch;
 }, {
     readonly id: "opentargets";
     readonly run: typeof collectOpenTargets;
@@ -101,5 +105,4 @@ export declare const COLLECTOR_MANIFEST: readonly [{
     readonly id: "therapeutic-programs";
     readonly run: typeof collectTherapeuticPrograms;
 }];
-export type CollectorId = (typeof COLLECTOR_MANIFEST)[number]["id"];
 export {};