R15

log/R15.md — Round 15 entries

Sub-file of log — see parent for index.

[2026-05-05] Round 15 — Hallmark causality graph synthesis MOC (DONE)

Deliverables

New framework pages (2):

• frameworks/hallmark-causality-graph.md — main synthesis MOC. Sections: the co-equality question, three lines of evidence (intervention epistasis, genetic epistasis, temporal precedence), proposed three-tier hierarchy (proximal / intermediate / integrative), directed edge summary, disagreements with López-Otín and SENS frameworks, three genuine open ordering questions, intervention sequencing implications. No verified field (framework schema). Auto-extraction banner 2026-05-05.
• frameworks/causal-graph-data.md — companion edge table (34 rows). Columns: upstream-hallmark, downstream-hallmark, evidence-strength, key-citation, wiki-page-evidence. Totals: 11 strong edges, 17 moderate, 3 weak, 1 disputed (mito-dysfunction ↔ cellular-senescence bidirectional/contested). Node outbound/inbound count summary tables included.

Hallmark frontmatter updates (12 pages):

caused-by: and causes: arrays populated on all 12 hallmark pages with citation-backed directed edges derived from verified atomic pages. Also added ”## Position in causal hierarchy” body section to each page.

Hallmark	caused-by count	causes count
genomic-instability	1 (telomere-attrition)	3
telomere-attrition	1 (genomic-instability)	3
epigenetic-alterations	2	2
cellular-senescence	5	3
deregulated-nutrient-sensing	0	5
disabled-macroautophagy	1	3
loss-of-proteostasis	3	1
mitochondrial-dysfunction	3	3
chronic-inflammation	6	2
altered-intercellular-communication	4	1
stem-cell-exhaustion	9	3
dysbiosis	2	2

Bidirectional consistency

Ran automated YAML-parse consistency check (yaml.safe_load). Found 1 inconsistency at completion:

• telomere-attrition.causes included genomic-instability (dysfunctional telomeres → end-to-end chromosome fusions → breakage-fusion-bridge cycles amplify genomic instability); genomic-instability.caused-by did not include telomere-attrition. Fixed: genomic-instability.caused-by updated to ["[[telomere-attrition]]"].

Post-fix: all 34 edges in causal-graph-data.md are bidirectionally consistent across the 12 hallmark pages.

Schema decisions

• Framework pages do not carry verified fields (R14 precedent confirmed).
• Disputed bidirectional edge (mito-dysfunction ↔ cellular-senescence) represented in both directions in the data table with disputed evidence-strength and a notes column entry referencing MiDAS literature.
• Chronic-inflammation placed at integrative tier with high tractability — anomalous but defensible (CANTOS clinical proof-of-concept without upstream reversal).
• New implicit stubs created: [[clonal-hematopoiesis]], [[neurodegeneration]], [[sarcopenia]], [[immunosenescence]], [[atherosclerosis]] (appear in causes: arrays as downstream non-hallmark nodes; no pages seeded yet).

Gaps surfaced

• #gap/needs-replication on clonal-hematopoiesis as genomic-instability → chronic-inflammation mechanistic intermediate.
• #gap/contradictory-evidence on mito-dysfunction ↔ cellular-senescence direction.
• Open ordering questions documented on synthesis MOC: (1) epigenetic → stemness vs stemness → epigenetic, (2) mito → senescence vs senescence → secondary mito, (3) dysbiosis → inflammation vs inflammation → dysbiosis temporal direction.