Research evidence interface — not a medical device, not a cure claim, not a protocol

Working thesis chapter · 19 September 2026 · computational research

CONFLUENCE: An Evidence-Gated Dynamical Framework for Integrating Oncology Knowledge, Molecular Observations and Adaptive Cancer-State Modeling

Branch feat/onco-adapter-p0 · PR #9. Page date 19 September 2026. Statistics keep their original estimate year.

Scope (Gate 0). CONFLUENCE is a computational research framework. Current results are computational unless an external experiment is cited. Not a clinical decision-support system. Not a universal cure. Simulated trajectories are not patient outcomes.

Abstract

Cancer research now produces knowledge graphs, multi-omic assays and dynamical simulators in parallel. The failure mode is collapsing those layers. This study asks whether a provenance-controlled pipeline can keep the layers apart while still allowing testable predictions. Scientific success is a staged chain — traceability, mathematical validity, identifiability, out-of-sample prediction, experimental falsification — not disease eradication. PR #9 is architectural evidence for the gates, not therapeutic efficacy.

Why the study is necessary

GLOBOCAN 2024 estimates, published 2026: about 20.6 million diagnoses and 9.8 million deaths [1,2] (EVID-001). Breast cancer about 2.43 million new cases [1,2] (EVID-002). WHO: many cancers can be cured if found early and treated well; access is uneven [3] (EVID-003). Nigeria GLOBOCAN 2022 profile: 127,763 new cases, 79,542 deaths, breast 32,278 — 2022 estimates, not 2026 incidence [5] (EVID-004).

Tumours evolve and adapt under therapy [7] (EVID-006). Multi-omics increase resolution without automatically producing a causal model. Mathematical oncology supplies in-silico laboratories [8] (EVID-007). Adaptive therapy treats treatment as a process under selection [9] (EVID-008). The gap is connecting knowledge to dynamical hypotheses without dropping provenance.

Evidence for the problem

TNBC is a test case because NCI describes it as roughly 15% of breast cancers, typically faster-growing and more recurrent, and heterogeneous [6] (EVID-005). That is not a CONFLUENCE parameter. This branch adds a read-only OnCo adapter with nine tests that refuse knowledge-as-parameter and do not edit CancerODE [11] (EVID-009). OnCo is a cited knowledge graph, not Theta [10].

Knowledge ≠ Evidence ≠ Causal mechanism ≠ Parameter ≠ Prediction

legacy gene→parameter map ≠ identified parameter · structured representation ≠ biological observation

Problem statement

How can heterogeneous oncology knowledge and molecular observations be incorporated into a cancer dynamical model without collapsing evidence, mechanism, parameterisation and prediction into unsupported assumptions?

Knowledge → Evidence → Hypothesis → Mechanism → Parameter → Prediction → Experiment → New evidence

Every arrow is a failure point. A page may motivate a hypothesis; it must not become Theta.

Significance of the study

Scientific

Treat cancer as dynamic and adaptive rather than as independent targets [7] (EVID-006).

Methodological

Evidence gates. OnCo confidence is not P(H). Idea maturity is not evidence level. Failed hypotheses stay visible [10,11].

Computational

Auditable objects. PR #9 is the current artifact [11] (EVID-009).

Translational potential — not demonstrated benefit

Models can compare hypotheses before a wet experiment. This page does not claim patient benefit. Translation waits for Gates 6–8.

Future research

Attach genomic, single-cell, spatial, PK/PD and controllers around a frozen biological model.

CONFLUENCE evidence architecture

Oncology knowledge (OnCo, literature)
        ↓ read-only adapter
Evidence objects → genomic / molecular observation → cellular state
        ↓
Population dynamics — frozen confluence_v2_15d → controller → prediction → experiment → evidence

Lineages frozen: tnbc_mod_3s (ROS audit pending), confluence_report_6s (paper), confluence_v2_15d (live ODE), confluence_v1_calibrator (legacy map, assumed / unidentified).

Success protocol

Not a universal cure. Sequential and falsifiable:

Gate 0Research-only scope.
Gate 1Provenance: source, URI, date, population.
Gate 2Evidence class named.
Gate 3Mechanism: intervention, state, sign, context, falsifier.
Gate 4Parameter: model id, symbol, units, estimator, uncertainty, identifiability. Unidentified ≠ established.
Gate 5Prediction labelled as computational.
Gate 6Held-out / external / baseline validation.
Gate 7An experiment that could show the prediction is wrong.
Gate 8Translation only after biological and clinical validation this repository does not claim.

Traceability → mathematical validity → identifiability → out-of-sample prediction → experimental falsification.

Three-arm programme — hypotheses, not results

validation/validation_protocol.md states H0 versus H1. Thresholds such as r > 0.5 are protocol criteria, not findings [12] (EVID-010).

Arm 1 · planned / ongoing hypothesis

Separate validation

Cancer and metabolic systems independently.

Arm 2 · planned / ongoing hypothesis

Conjoined validation

Coupled versus independent models on comorbidity data.

Arm 3 · planned / ongoing hypothesis

Universality test

Whether ΔΦ distributions match after labels are stripped — against nulls.

Evidence ledger

Each row keeps year and population. Numbered Vancouver-style references appear in the text as [n] and in the list below. Ledger ids (EVID-xxx) are the machine-readable claim keys. Citation rules: docs/CITATION_POLICY.md. Audit is server-side; the API key never enters this page.

Loading claims.json…

Grok Evidence Auditor

Grok output is an evidence-audit aid. Not a truth score, not a parameter estimator, not expert review. Citations still load from the ledger when the auditor is offline.

Limitations and falsifiers

References

  1. Sung H et al. Global cancer statistics 2024. CA Cancer J Clin. 2026. doi:10.3322/caac.70090
  2. IARC. GLOBOCAN 2024 news. 8 July 2026. iarc.who.int
  3. WHO. Cancer fact sheet. 2026. who.int
  4. WHO. Global status report on cancer 2026. 9789240123977
  5. IARC. Nigeria fact sheet (GLOBOCAN 2022). gco.iarc.who.int
  6. NCI. Triple-negative breast cancer. cancer.gov
  7. NCI. Tumour heterogeneity. cancer.gov
  8. Altrock PM, Liu LL, Michor F. The mathematics of cancer. Nat Rev Cancer. 2015. PMC5663316
  9. Gatenby RA et al. Adaptive therapy. Cancer Res. 2009. PMC2676449
  10. Gomila J et al. OnCo. onco.cc
  11. Ogbonna K. Project Confluence PR #9. pull/9
  12. Validation protocol. validation_protocol.md

OnCo data CC BY-NC 4.0 where cited [10]. Numbered references are Vancouver-style; DOIs are included only when verified. Not medical advice. See DISCLAIMER.md.