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Open Enzyme Dependency Graph

This graph is a compact routing surface for current decisions. It does not rank interventions, chassis, UOX sequences, topologies, or product formats. Scientific evidence and limitations live in the linked topic pages.

Portfolio map

flowchart TD
    M["Mission: identify exploitable gout weaknesses and test engineered exploits"]
    S["System map: urate production, transport, crystallization, inflammation, and resolution"]
    P["Portfolio of independently falsifiable tracks"]

    T1["Urate-production and transporter tracks"]
    T2["Luminal UOX hypothesis"]
    T3["Local-tissue and systemic UOX routes"]
    T4["Inflammation and resolution tracks"]
    T5["Other disposal and delivery mechanisms"]

    M --> S
    S --> P
    P --> T1
    P --> T2
    P --> T3
    P --> T4
    P --> T5

The system map routes questions to distinct tests. Evidence for one route does not transfer to another, and failure of one track does not stop the portfolio.

Luminal UOX decision path

flowchart TD
    H08["H08: luminal UOX sink remains an open hypothesis"]
    C44["comp-044: legacy unconditional flat-dose classification was not robust to the tested diagnostics"]
    C50["comp-050: conditional capacity and measurement-identifiability map; biological regime not evaluated"]
    V["Candidate UOX sequences remain unranked"]
    CH["Candidate yeast, koji, bacterial, and cell-free configurations remain unranked"]
    B["Verified matched constructs: identity, active UOX, localization, process retention, and controls"]
    G133["§1.33: configuration-level physiological substrate × oxygen × peroxide"]
    G136["§1.36: urate antioxidant loss × H2O2 × epithelial safety"]
    NEXT["Later dynamic modeling and translational study design"]
    REDIRECT["Stop or redesign only the failed configuration"]

    H08 --> C44
    C44 --> C50
    C50 -->|"method map defines empirical closure"| G133
    V --> B
    CH --> B
    B --> G133
    G133 -->|"passes matched reaction-site rule"| G136
    G133 -->|"fails"| REDIRECT
    G136 -->|"supports further study"| NEXT
    G136 -->|"fails"| REDIRECT

What the edges mean

  • comp-044 → §1.33: COMP-019's unconditional flat-dose classification is not robust to COMP-044's tested substrate-occupancy and finite-window diagnostics. That result is a Deterministic Computational Audit, not mechanistic biological validation. Routing the unresolved substrate, oxygen, localization, and peroxide constraints into §1.33 is Mechanistic Extrapolation. The audit supplies no replacement ΔSUA, dose, genotype order, physiological regime, efficacy model, topology/chassis selection, production-sufficiency target, or safety conclusion.
  • comp-050 → §1.33 and later ledger work: concentration alone cannot identify local UOX removal. Qualified product fate and calibrated reaction-site capacity characterize local configuration performance. Source influxes, reabsorption, outflow, and source-resolved product fate make the declared ledger structurally reconstructible; the unattributed residual is then calculated algebraically and practical closure requires it to pass a prespecified tolerance. This is a deterministic structural-identifiability result, not assay validation or biological evidence.
  • Construct build → §1.33: protein mass, transcript, promoter strength, or activity at a high-substrate benchmark is insufficient. The decision variable is reproducible active UOX at the intended reaction site under the matched physiological test.
  • §1.33 → §1.36: only an exact configuration with product formation at the human-baseline prior, without a prespecified extracellular-H2O2 or viability penalty relative to matched controls, advances to the dedicated epithelial-safety test. A topology conclusion is transferable only within a controlled host comparison.
  • §1.36 → later work: lower H2O2 alone does not pass if barrier injury persists after urate removal. A pass supports designing the next study; it does not establish a human dose or serum-urate effect.
  • Failure → redirect: a failed sequence, topology, chassis, or process updates only that tested configuration.

Evidence and decision homes