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

Thesis #1 · 20 September 2026 · computational research

CONFLUENCE × OnCo: An Evidence-Gated Dynamical Framework for Integrating Oncology Knowledge Graphs with Adaptive Cancer-State Models

Kelechi Emeka Ogbonna

Independent computational research / Project Confluence (GitHub cloudynirvana) · 20 September 2026. Statistics keep their original estimate year.

Download citeable PDF · branch feat/onco-adapter-p0 · PR #9. This document has no DOI.

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 [10,53,61]. 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 [43-52]. PR #9 is architectural evidence for the gates, not therapeutic efficacy [11,56]. GLOBOCAN 2024 estimates, published 2026, report about 20.6 million diagnoses and 9.8 million deaths; that statistic is context, not a CONFLUENCE parameter [1,2,64].

Why the study is necessary

GLOBOCAN 2024 estimates, published 2026: about 20.6 million diagnoses and 9.8 million deaths [1,2,64] (EVID-001). Breast cancer about 2.43 million new cases [1,2] (EVID-002). The 2024/2026 series continues earlier GLOBOCAN editions [54,55]. WHO: many cancers can be cured if found early and treated well; access is uneven [3,4] (EVID-003). Nigeria GLOBOCAN 2022 profile: 127,763 new cases, 79,542 deaths, breast 32,278 — 2022 estimates, not 2026 incidence [5] (EVID-004).

Cancer is organised as acquired hallmarks rather than a single defect [13-15]. Tumours evolve clonally and adapt under therapy [7,16,17] (EVID-006). Intra-tumour heterogeneity and branched evolution complicate response prediction [18-21]. The tumour microenvironment recruits stromal and immune cells, including T-cell exclusion and exhaustion states [22-27]. Multi-omics increase resolution without automatically producing a causal model [20,43]. Mathematical oncology supplies in-silico laboratories [8,39] (EVID-007). Adaptive therapy treats treatment as a process under selection [9,40,41] (EVID-008). The gap is connecting knowledge to dynamical hypotheses without dropping provenance [10,11,57].

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 [6,28-31] (EVID-005). That is not a CONFLUENCE parameter [56,63]. This branch adds a read-only OnCo adapter with nine tests that refuse knowledge-as-parameter and do not edit CancerODE [11,58] (EVID-009). OnCo is a cited knowledge graph, not Theta [10,61]. Biomedical knowledge graphs more generally integrate assertions; they remain literature until an identification step [53].

Warburg / LDHA — interesting, still not a parameter

Aerobic glycolysis is a classical cancer-cell observation [32-35]. Lactate can polarise macrophages and blunt T- and NK-cell surveillance [36-38,42]. OnCo listing LDHA therefore has a literature context. It still does not identify p_lactate [10,11,36,63].

Knowledge ≠ Evidence ≠ Causal mechanism ≠ Parameter ≠ Prediction

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

1. Problem Statement

How can heterogeneous oncology knowledge-graph records and molecular observations be incorporated into a frozen cancer dynamical model without collapsing knowledge, evidence, mechanism, parameterisation, and prediction into unsupported assumptions [10,45-53,57,61]?

That is a computational and medical-methods problem. It is not a claim to treat, dose, or cure patients [3,56].

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 [45,47,51,57].

2. Justification of the Study

Existing integration habits fail by overclaiming (GLOBOCAN/WHO figures are context, not Θ [1-4,56,64]), by parameter smuggling (OnCo LDHA or the legacy gene-to-parameter map as p_lactate [10,11,36,58,63]), and by missing identifiability gates [45-52,57]. PR #9 is architectural evidence for the refusal, not therapeutic efficacy [11,56].

3. Significance of the Study

Scientific

Treat cancer as dynamic and adaptive rather than as independent targets [7,13-17] (EVID-006). Significance is for researchers, not a clinic [56].

Methodological

Evidence gates. Structural and practical identifiability are refusal rules, not a new proof for confluence_v2_15d [45-52]. OnCo confidence is not P(H). Idea maturity is not evidence level. Failed hypotheses stay visible [10,11,57].

Computational

Auditable objects. PR #9 is the current artifact [11,58,60] (EVID-009).

Not clinical CDS / not a cure

Models can compare hypotheses before a wet experiment [8,39]. This page does not claim patient benefit [56]. Translation waits for Gates 6–8 [3,12].

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) [62], confluence_report_6s (paper) [60], confluence_v2_15d (live ODE) [11,58], confluence_v1_calibrator (legacy map, assumed / unidentified) [63]. Public claims follow the citation policy [59]. Systems-biology identifiability literature defines Gate 4; it is not a new proof for this ODE [43,44,45-52].

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). Adaptive-therapy controllers remain in-silico research arms [9,40,41,56].

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 (same numbering as the manuscript and PDF). Ledger ids (EVID-xxx) are the machine-readable claim keys. Citation rules: docs/CITATION_STYLE.md and 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

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OnCo data CC BY-NC 4.0 where cited [10,61]. Numbered references are Vancouver-style and match the manuscript. DOIs are included only when verified on Crossref or PubMed. Not medical advice. See DISCLAIMER.md [56].