Vaccine Mechanisms & Immunization Curation

Overview & Design Principle

In dismech, vaccines are not modeled as opaque "preventive checkboxes" detached from disease biology. Instead, every vaccine entry in a disorder's treatments: block is modeled as a causal intervention (MechanismLink) that inhibits, modulates, or activates a specific node in the disorder's pathophysiology: causal graph.

Whether a vaccine induces secretory IgA that neutralizes viral attachment at the brush border, systemic IgG that neutralizes a bacterial exotoxin without preventing mucosal colonization, opsonizing antibodies against a polysaccharide capsule, or cytotoxic CD8+ T cells targeting viral oncoproteins or tumor neoantigens, the target_mechanisms: edge explicitly records which step of the pathograph the vaccine intercepts and why.

0. Ontology & Schema Architecture (Why Not VO?)

Why We Use NCIT Instead of the Vaccine Ontology (VO)

Dismech deliberately consolidates all medical actions, procedures, and biological/vaccine agents onto NCI Thesaurus (NCIT), ChEBI (CHEBI), and MAXO (MAXO) rather than importing the OBO Vaccine Ontology (VO):

1. Unified medical action hierarchy (TreatmentDescriptor): In src/dismech/schema/model.yaml, treatment_term.term is validated against NCIT medical procedures (Vaccination NCIT:C15346, Passive Immunization NCIT:C15259) or MAXO, while specific vaccine formulations and biologics sit under NCIT:C1909 (Pharmacologic Substance $\rightarrow$ NCIT:C923 Vaccine) in treatment_term.therapeutic_agent.
2. Avoids OAK / BioPortal cache fragmentation: Maintaining a single OAK validation surface (cache/ncit/terms.csv) covers small molecules, monoclonal antibodies, toxoids, conjugate vaccines, mRNA-LNP vaccines, and live-attenuated viral vaccines without cross-ontology duplication.
3. Environmental / adverse-event exposures use ECTO: When vaccination is modeled as an environmental exposure or trigger (e.g., live-vaccine disseminated disease in an inborn error of immunity, or post-vaccination immune-mediated sequelae), dismech uses ECTO:2000129 (exposure to vaccination) in the environmental: block.

Canonical YAML Pattern for Vaccine Treatments

treatments:
- name: Rotavirus Vaccination
  description: Oral live-attenuated rotavirus vaccines (pentavalent human-bovine reassortant
    RV5 or monovalent human-attenuated RV1) administered in infancy induce mucosal
    secretory IgA and neutralizing antibodies against outer-capsid proteins VP4 and
    VP7, preventing severe dehydrating rotaviral gastroenteritis.
  therapeutic_modality: VACCINE
  delivery_system: VIRAL_VECTOR # Optional: LIPID_NANOPARTICLE, VIRAL_VECTOR, PROTEIN_CONJUGATE, etc.
  treatment_term:
    preferred_term: vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
    therapeutic_agent:
    - preferred_term: rotavirus vaccine
      term:
        id: NCIT:C96394
        label: Rotavirus Vaccine
  target_mechanisms:
  - target: Rotavirus Attachment and Mature Enterocyte Invasion
    treatment_effect: INHIBITS
    description: Mucosal secretory IgA and serum neutralizing antibodies against VP4
      (VP8*/VP5*) and VP7 block virion attachment and entry into mature small-intestinal
      villus enterocytes and neutralize NSP4 enterotoxin activity.
    evidence:
    - reference: PMID:32644377
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Vaccination is the best way to prevent rotavirus disease."
      explanation: Supports oral rotavirus vaccination as the primary prophylactic
        intervention preventing rotavirus infection and severe dehydrating enteritis.

Schema Slots Touching Vaccines

0b. MHC Restriction Ontology (MRO) & IEDB Integration

Why MRO (IEDB's MHC Restriction Ontology) Was Integrated

Across vaccine-preventable diseases, autoimmune diseases, infectious diseases, and drug hypersensitivity entries, MHC/HLA restriction is one of the strongest genetic determinants of both disease susceptibility and vaccine / immunotherapy responsiveness: - Many clinically important HLA entities are multi-gene heterodimers (HLA-DQ2.5 encoded by HLA-DQA1*05:01 + HLA-DQB1*02:01, MRO:0000019) or multi-locus serotypes (HLA-DQ2 serotype MRO:0000283, HLA-B27 serotype MRO:0000129, HLA-DR4 serotype MRO:0000303) that cannot be faithfully represented by a single HGNC gene CURIE. - IEDB (Immune Epitope Database) maintains MRO (http://purl.obolibrary.org/obo/MRO_) specifically to represent MHC protein complexes, serotypes, mutant complexes, and alpha/beta chains, and anchors its hierarchy directly under GO:0042611 (MHC protein complex).

How MRO Works in the Dismech Schema

1. Pathophysiology.protein_complexes (ProteinComplexTerm): Because ProteinComplexTerm already has GO:0042611 (MHC protein complex) in reachable_from, routing MRO: ols:mro in conf/oak_config.yaml automatically enables protein_complexes to bind any MRO MHC class I/II protein complex (MRO:0001284 HLA-DRB1*03:01 protein complex, MRO:0001007 HLA-B*57:01 protein complex, MRO:0000019 HLA-DQA1*05:01/DQB1*02:01 protein complex).
2. Genetic.mhc_term (MHCDescriptor $\rightarrow$ MHCTerm): Allows genetic: entries to pair a locus gene_term (hgnc:4942 HLA-DQA1) with the exact serotype or heterodimer (MRO:0000283 HLA-DQ2 serotype) or to bind a multi-locus serotype directly.
3. TreatmentEffectModifier.mhc_term (MHCDescriptor $\rightarrow$ MHCTerm): Allows treatments[].effect_modifiers[] with effect_modifier_type: GENOTYPE to bind the exact HLA restriction complex that modifies vaccine seroconversion (e.g., HLA-DRB1*03:01 / HLA-DRB1*07:01 non-responder haplotypes in Hepatitis_B vaccination) or requires an HLA-restricted peptide/TCR vaccine (e.g., HLA-A*02:01-restricted cancer vaccines).

treatments:
- name: Hepatitis B Vaccination
  therapeutic_modality: VACCINE
  effect_modifiers:
  - effect_modifier_type: GENOTYPE
    stratum: HLA-DRB1*03:01 carriers
    mhc_term:
      preferred_term: HLA-DRB1*03:01 protein complex
      term:
        id: MRO:0001284
        label: HLA-DRB1*03:01 protein complex
    comparator_stratum: non-carriers
    modified_outcome: anti-HBs seroprotection rate
    effect_in_stratum: SMALLER_EFFECT

Broader IEDB Opportunities

• Structured Source (IEDB:<epitope_id>): Extending StructuredSourceId in src/dismech/schema/common.yaml to support IEDB:\d+ for experimentally validated neutralizing B-cell and T-cell epitopes (e.g., Rotavirus VP8*/VP7, SARS-CoV-2 Spike RBD, HPV E6/E7, DNAJB1-PRKACA fusion neoantigen).
• Molecular Mimicry & Cross-Reactivity: Linking pathogen epitope IDs to host autoantigen mimics in Guillain-Barre_Syndrome, Acute_Rheumatic_Fever, Type_1_Diabetes, and Celiac_Disease.
• Cross-Repo Bridge to ~/repos/ai-gene-review: Mapping viral protein UniProt accessions (ROTA/VP4, ROTA/VP7, SARS2/SPIKE) to IEDB parent protein immunodominant regions.

1. Six Mechanistic Archetypes for Vaccines in Dismech

Connecting a vaccine via target_mechanisms: forces the curator to distinguish where in the pathograph immunity acts:

1. Viral Attachment, Entry & Mucosal Establishment Blockade - Mechanism: Neutralizing antibodies (secretory IgA at mucosal surfaces or systemic IgG) bind viral attachment/fusion proteins (e.g., HPV L1 capsid, SARS-CoV-2 Spike RBD, Rotavirus VP4/VP7, Rabies glycoprotein G, HAV capsid), blocking host-receptor engagement (ACE2, HSPG, HBGA, NCAM1/CHRN) and early cellular entry. - Exemplars: Human_Papillomavirus_Infection (Prophylactic L1 VLP vaccine), Immunodeficiency_74_COVID-19-related_X-linked (SARS-CoV-2 mRNA vaccine), Rabies (post-exposure vaccine blocking retrograde axonal transport), Hepatitis_A, Hepatitis_D (HBV vaccine preventing HBsAg helper virus acquisition).

2. Toxoid / Antitoxin Neutralization (Disease Prevention Without Colonization Blockade) - Mechanism: Formalin-inactivated or genetically detoxified bacterial/plant toxoids elicit systemic IgG against the secreted A-B exotoxin or superantigen (Diphtheria toxin, Tetanus neurotoxin, Pertussis toxin, Anthrax protective antigen, TSST-1, Ricin A chain). Crucially, the vaccine targets the toxin-mediated tissue injury or receptor-entry node, not the mucosal colonization node. - Exemplars: Diphtheria, Anthrax, Toxic_Shock_Syndrome, Ricin_Poisoning.

3. Polysaccharide-Protein Conjugate Opsonophagocytosis & Mucosal Carriage Reduction - Mechanism: Conjugating a bacterial capsular polysaccharide (T-cell-independent antigen, e.g., Hib PRP, pneumococcal serotypes, meningococcal A/C/W/Y) to a carrier protein (CRM197, tetanus toxoid) recruits CD4+ Tfh cells (germinal_center_reaction module), driving class-switched, affinity-matured anti-capsular IgG and mucosal IgA that overcome capsular complement evasion and reduce nasopharyngeal carriage. - Exemplars: Haemophilus_Meningitis, Pneumococcal_Meningitis, Streptococcal_Meningitis.

4. Therapeutic & Neoantigen Vaccines (Cell-Mediated Clearance of Infected or Transformed Cells) - Mechanism: Once viral genomes integrate or somatic driver mutations establish a clone, neutralizing antibodies against surface capsids are ineffective. Therapeutic peptide/mRNA/DC vaccines target intracellular oncoproteins or fusion neoantigens (HPV E6/E7, DNAJB1-PRKACA chimera, MUC1) presented on MHC class I/II to prime CD8+ cytotoxic T lymphocytes and Th1 cells. - Exemplars: Human_Papillomavirus_Infection (Therapeutic HPV Vaccination (E6/E7-directed)), Fibrolamellar_Hepatocellular_Carcinoma (DNAJB1-PRKACA Fusion-Neoantigen Peptide Vaccine), Colon_Adenocarcinoma (MUC1 Peptide Vaccine).

5. Host-Vulnerability Bypass & Decompensation-Trigger Prevention - Mechanism: In inborn errors of immunity (TLR7, MyD88, C1Q, C2 deficiencies) or acute febrile/viral decompensation syndromes (RANBP2 ANE1, LARS1 ILFS1, TNNI3K cardiomyopathy), vaccination either bypasses the defective innate sensor via an orthogonal adjuvant/PRR pathway (MDA5/TLR3 for mRNA-LNP in TLR7 deficiency) or prevents the upstream febrile/viral infection trigger that initiates organ failure. - Exemplars: Immunodeficiency_74_COVID-19-related_X-linked, C1Q_Deficiency, Complement_Component_2_Deficiency, MyD88_Deficiency, Familial_Acute_Necrotizing_Encephalopathy, Infantile_Liver_Failure_Syndrome_1.

6. Live-Vaccine Pathogenicity & Contraindication in Primary Immunodeficiencies - Mechanism: Live-attenuated vaccines (BCG, oral poliovirus, rotavirus, MMR, yellow fever) replicate unchecked when a critical host restriction pathway is absent (e.g., IFN-gamma/IL-12 axis in Mendelian Susceptibility to Mycobacterial Disease, STAT1/STAT2/IRF9 type I IFN signaling, or severe combined immunodeficiency). Here, the vaccine strain is represented in pathophysiology: / environmental: (ECTO:2000129) as a causal trigger of disseminated vaccine-strain infection.

2. Exemplar Entries Currently in the KB

3. Flagship New-Disorder Trial: Rotaviral Enteritis (MONDO:0005194)

Rotaviral_Enteritis (MONDO:0005194, rotaviral enteritis) is our primary end-to-end curation trial integrating: 1. Viral pathogenesis across dual secretory + osmotic diarrhea mechanisms, 2. Host genetic receptor dependency (FUT2 secretor status), and 3. Vaccine mechanism links (NCIT:C96394 Rotavirus Vaccine).

Planned Causal Pathograph (kb/disorders/Rotaviral_Enteritis.yaml)

flowchart TD
  G1["Host FUT2 Secretor Status (hgnc:4013)<br/>Alpha(1,2)-fucosylated HBGA expression on villus enterocytes"] --> N1
  N1["Host Glycan Attachment and Mature Villus Enterocyte Entry<br/>VP4 (VP8*/VP5*) & VP7 outer capsid bind HBGAs/sialoglycans"]
  N1 --> N2["NSP4 Viroporin-Mediated Intracellular Calcium Mobilization<br/>Endoplasmic reticulum Ca2+ mobilization & Calcium-Activated Chloride Secretion (ANO1) + ENS stimulation"]
  N1 --> N3["Proteasomal DGAT1 Degradation and Villus Enterocyte Destruction<br/>Villus blunting, lactase/sucrase-isomaltase depletion, carbohydrate malabsorption"]
  N1 --> N4["Cytoplasmic Replication and Innate Antiviral Antagonism<br/>Viroplasm assembly, NSP1 PRR antagonism & Systemic Antigenemia and Transient Viremia"]
  N2 --> P1["Secretory Diarrhea (HP:0005208)"]
  N3 --> P3["Malabsorptive Osmotic Diarrhea (HP:0033310) & Secondary Lactase Deficiency (HP:0002024)"]
  P1 --> P2["Dehydration (HP:0001944) & Metabolic Acidosis (HP:0001942)"]
  P3 --> P2
  V1["Oral Live-Attenuated Rotavirus Vaccine (NCIT:C96394)<br/>RV5 (RotaTeq) / RV1 (Rotarix)"] -. "INHIBITS (Mucosal sIgA anti-VP4/VP7 & anti-VP6)" .-> N1
  V1 -. "INHIBITS (Prevents NSP4 enterotoxin activity)" .-> N2
  V1 -. "INHIBITS (Preserves DGAT1 & villus enterocytes)" .-> N3

4. Coordination with ~/repos/ai-gene-review (Host vs. Viral Genes)

Dismech integrates with ~/repos/ai-gene-review via src/dismech/ingest/genes.py (just genes-ingest-build, outputting app/genes-data.js), which joins gene symbols across both repositories. Because dismech currently validates GeneDescriptor.term against the human HGNC cache (cache/hgnc/terms.csv), host and viral genes follow a coordinated two-sided convention:

Side A: Host Receptor, Restriction & Susceptibility Genes (Direct HGNC $\leftrightarrow$ UniProt Join)

Human host genes that mediate viral attachment, entry, innate sensing, or vaccine responsiveness are curated in kb/genes/<SPECIES>/<SYMBOL>/<SYMBOL>-ai-review.yaml (HUMAN taxon NCBITaxon:9606) in ai-gene-review and referenced via hgnc:<ID> in the dismech disorder's genetic: and pathophysiology[].genes: blocks:

Side B: Viral Antigen & Effector Genes (Viral Taxon Directories in ai-gene-review)

In ~/repos/ai-gene-review/kb/genes/, viral proteins are curated under their viral taxon proteome codes (e.g., SARS2/SPIKE, TYPH/E6, TYPH/E7, EBVG/LMP1, and for Rotavirus A: ROTA/VP4, ROTA/VP7, ROTA/NSP4, ROTA/NSP1).

• Current Rule in Dismech: Never force a viral gene symbol into genes: with a fake hgnc: CURIE. Instead: 1. Name the viral protein and its UniProt accession in the Pathophysiology.description and Treatment.target_mechanisms[].description (e.g., VP4 [VP8*/VP5*], VP7, NSP4). 2. Bind the exact shared GO biological_processes terms on the Pathophysiology node that ai-gene-review annotates as core_functions on the viral gene (GO:0046718 viral entry into host cell, GO:0019062 virion attachment to host cell, GO:0039503 suppression by virus of host innate immune response).
• Planned Schema & Ingest Enhancement: Add an optional pathogen_genes (or uniprot:-backed GeneDescriptor) slot on Pathophysiology and MechanismLink and extend src/dismech/ingest/genes.py (load_gene_kb) to join non-human viral UniProt records from ai-gene-review directly onto disorder pathograph nodes and vaccine target_mechanisms.

5. Conserved Mechanism Modules (kb/modules/)

Vaccine mechanisms reuse and motivate conserved modules in kb/modules/:

• Existing Modules:
• germinal_center_reaction: Tfh-driven B-cell somatic hypermutation, affinity maturation, and generation of long-lived plasma cells (NIH_HT_22_short_lived_long_lived_plasma_cells) and memory B cells; underlies conjugate and protein/mRNA vaccine durability.
• cgas_sting_pathway_activation & innate_antiviral_interferon_response: Innate nucleic-acid sensing pathways activated by viral infection and vaccine adjuvants.
• host_directed_antiviral_dependency: Host factor dependency (entry receptors, proteases, replication factors) shared with viral entry blockade.
• Vaccine-Specific Modules (kb/modules/):
• vaccine_induced_mucosal_iga_neutralization: Oral/intranasal vaccine priming of Peyer's patch / NALT B cells, polymeric IgA transcytosis via PIGR, and luminal neutralization of enteric/respiratory pathogens (Rotaviral_Enteritis, Cholera, Paralytic_Poliomyelitis).
• polysaccharide_conjugate_t_dependent_switching: Carrier-protein conjugation converting bacterial capsular polysaccharides from T-independent B-cell antigens into MHC-II-restricted Tfh-dependent germinal center responses (Haemophilus_Meningitis, Meningococcal_Meningitis, Pneumococcal_Meningitis, Pneumococcal_Pneumonia).
• toxoid_neutralizing_humoral_immunity: Systemic IgG neutralization of secreted bacterial A-B exotoxins decoupling colonization from toxin-mediated organ injury (Diphtheria, Tetanus, Pertussis).

6. KB Audit: Vaccine-Preventable Diseases Wired with target_mechanisms

We audited all disorder entries with vaccine treatments and curated/enriched 28 vaccine-preventable disease (VPD) entries (including 6 newly curated VPD disorder entries: Rotaviral_Enteritis, Tick-Borne_Encephalitis, Yellow_Fever, Meningococcal_Meningitis, Herpes_Zoster, and Japanese_Encephalitis) so their vaccine treatments carry therapeutic_modality: VACCINE and explicit target_mechanisms: (treatment_effect: INHIBITS) pointing to the exact upstream nodes in pathophysiology:.

STATUS

Phase 1: Flagship New Vaccine-Preventable Disease (VPD) Curations

• [x] Curate Rotaviral_Enteritis (MONDO:0005194) with NCIT:C96394 (Rotavirus Vaccine), FUT2 (hgnc:4013) host secretor receptor dependency, ANO1 (hgnc:21625) chloride channel effector, and NSP4/VP4/VP7 pathograph nodes
• [x] Curate Yellow_Fever (MONDO:0020502) with live-attenuated 17D vaccine (NCIT:C96396) and viscerotropic/hepatocyte pathograph
• [x] Curate Herpes_Zoster (MONDO:0005609) with recombinant gE/AS01B subunit vaccine (Shingrix) restoring VZV-specific CD4+ T-cell immunity to inhibit dorsal-root-ganglion reactivation
• [x] Curate Meningococcal_Meningitis (MONDO:0018059) with MenACWY polysaccharide-protein conjugate and MenB factor H-binding protein (fHbp) vaccines
• [x] Curate Monkeypox (MONDO:0005849) with MVA-BN (Jynneos) orthopoxvirus cross-protective vaccination
• [x] Curate Japanese_Encephalitis (MONDO:0019209) and Tick-Borne_Encephalitis (MONDO:0017572) with inactivated/live-attenuated flavivirus vaccines
• [x] Curate Congenital_Rubella_Syndrome (MONDO:0017361) with live-attenuated rubella vaccination (MMR) inhibiting maternal viremia and transplacental teratogenesis

Phase 2: Wire Existing VPD Entries with target_mechanisms & therapeutic_agent

• [x] Human_Papillomavirus_Infection — Prophylactic L1 VLP vs. Therapeutic E6/E7 vaccination wired to distinct pathograph nodes
• [x] Immunodeficiency_74_COVID-19-related_X-linked — NCIT:C181140 (mRNA COVID-19 Vaccine) wired to early SARS-CoV-2 replication node
• [x] Diphtheria — NCIT:C91718 (Diphtheria Toxoid/Tetanus Toxoid Vaccine Adsorbed) & NCIT:C15259 (Passive Immunization) wired to antitoxin immunity node
• [x] Haemophilus_Meningitis, Pneumococcal_Meningitis, Streptococcal_Meningitis, Bacterial_meningitis — Conjugate vaccines wired to capsular evasion / colonization / BBB invasion nodes
• [x] Rabies, Anthrax, Hepatitis_A, Hepatitis_D, Toxic_Shock_Syndrome, Ricin_Poisoning — Vaccines wired via target_mechanisms
• [x] Fibrolamellar_Hepatocellular_Carcinoma, Colon_Adenocarcinoma, Vulvar_Carcinoma — Neoantigen / oncoviral cancer vaccines wired via target_mechanisms
• [x] Enrich COVID-19, Influenza, and Respiratory_Syncytial_Virus_Infection vaccine treatments with therapeutic_modality: VACCINE, specific NCIT therapeutic_agent terms, and target_mechanisms
• [x] Enrich childhood viral VPDs (Measles, Mumps, Rubella, Chickenpox, Paralytic_Poliomyelitis) with target_mechanisms
• [x] Enrich bacterial toxoid & enteric VPDs (Pertussis, Tetanus, Pneumococcal_Pneumonia, Cholera, Typhoid_Fever) with target_mechanisms and NCIT vaccine agent CURIEs
• [x] Enrich Hepatitis_B, Ebola_Virus_Disease_EVD, Malaria, and Transitional_Cell_Carcinoma (intravesical BCG) with therapeutic_modality: VACCINE and target_mechanisms
• [x] Add vaccine treatments and target_mechanisms to Dengue, Chikungunya, Monkeypox, Bacterial_meningitis, and Tuberculosis (BCG)
• [x] Batch 2 Track 1: Wire target_mechanisms (treatment_effect: INHIBITS) with verified evidence: blocks across 10 KB disorders with pathogen-matched VACCINE treatments (Adenovirus_Respiratory_Infection, Anal_Canal_Carcinoma, Cervical_Squamous_Cell_Carcinoma, Glanders, Gonorrhea, Hand_Foot_and_Mouth_Disease, Hantavirus_Hemorrhagic_Fever_with_Renal_Syndrome, Late_Complement_Component_Deficiency, Penile_Cancer, and Viral_Encephalitis) plus Rubella evidence grading repair
• [x] Batch 2 Track 2: Add evidence-backed vaccine/immunoprophylaxis entries and module conformance hooks across Hepatitis_E, Buruli_Ulcer, Clostridioides_difficile_Infection, Prostate_Adenocarcinoma, and Cutaneous_Melanoma

Phase 3: Cross-Repo ai-gene-review, MRO / IEDB & Module Integration

• [x] Integrate MRO (MHC Restriction Ontology, IEDB's native MHC ontology) into conf/oak_config.yaml, src/dismech/schema/dismech.yaml (MHCTerm, MHCDescriptor, Genetic.mhc_term, TreatmentEffectModifier.mhc_term, plus ProteinComplexTerm via GO:0042611), src/dismech/term_tooltips.py, and src/dismech/templates/disorder.html.j2
• [x] Seed cache/mro/terms.csv and annotate mhc_term on key HLA-restricted vaccine effect modifiers (Hepatitis_B HLA-DRB1*03:01 MRO:0001284 and HLA class II protein complex MRO:0001356)
• [ ] Coordinate HUMAN/FUT2 and ROTA/VP4, ROTA/VP7, ROTA/NSP4 gene reviews in ~/repos/ai-gene-review alongside Rotaviral_Enteritis.yaml
• [x] Create kb/modules/polysaccharide_conjugate_t_dependent_switching.yaml, kb/modules/vaccine_induced_mucosal_iga_neutralization.yaml, and kb/modules/toxoid_neutralizing_humoral_immunity.yaml and wire conforms_to across 10 VPD entries
• [ ] Prototype optional pathogen_genes (uniprot: CURIE) support in src/dismech/schema/model.yaml and src/dismech/ingest/genes.py so viral antigen targets join directly to ai-gene-review

NOTES

Useful Commands

# Validate a disorder entry after adding vaccine target_mechanisms
just validate kb/disorders/Rotaviral_Enteritis.yaml

# Verify term labels against NCIT / HGNC / GO caches
just validate-terms-file kb/disorders/Rotaviral_Enteritis.yaml

# Rebuild browser + project pages
just render-projects