# EAC Dual-Arm Preprint — Deliverable Bundle

Manuscript Architect output for the esophageal adenocarcinoma (EAC) dual-arm drug program. **All results are computational (in-silico); no experimental validation has been performed.** Every quantitative claim traces to an upstream program artifact or a verified public source (see `claims_to_sources.csv`, `references.md`).

## The four bundled deliverables
1. **Executive summary** — `executive_summary.md` (one page: what the paper does, the two leads, key numbers, honest verdict).
2. **Manuscript + supplements** — `manuscript_v3_bundle.md` (acceptance-ready v3: abstract, intro, results, methods, discussion, 4 main figures + Fig S1, figure legends, and full Supplementary Information S0–S7). Component files: `manuscript_v3.md`, `supplementary_information_v3.md`, `figure_legends_v3.md`, plus supplementary tables `S1`–`S5` (CSV) and figures.
3. **Peer-review report** — `peer_review_report_combined.md` (both rounds: editor letters, all reviews, authors' responses, and a full revision-tracking table). Round 1 Major → Round 2 Minor revision, unanimous.
4. **Lay abstract** — `lay_abstract.md` (plain-language summary for non-specialists).

## Figures
- `figure1.png` — EAC genomics + competitive whitespace + dual-arm trajectory strategy
- `figure2.png` — honest druggability triage (GPX7 tops raw score but isn't binder-addressable; GUCY2C/DKK1 emerge)
- `figure3.png` — de novo binder design pipeline + in-silico validation (adopted from the program's design-results panel)
- `figure4.png` — predicted lead binder–target complexes with coordinate-derived interfaces (single-model, annotated)
- `figureS1_gtex.png` — normal-tissue selectivity of leads vs comparators (GTEx v8)

## Verification & provenance
- `references.md` — 8 external citations, all resolved to primary papers and checked (CrossRef/OpenAlex; none retracted)
- `claims_to_sources.csv` — claim → manuscript location → source trace
- Supplementary tables: `S1_binder_designs.csv`, `S2_target_nomination.csv`, `S3_competitive_landscape.csv`, `S4_gtex_selectivity.csv`, `S5_binder_liabilities.csv`

## Honest-verdict note
The paper's framing matches its evidence: pilot-scale in-silico leads, not validated therapeutics. Two make-or-break questions (GUCY2C normal-GI window O-2; DKK1 surrogate endpoint O-4) and the decisive near-term computational check (orthogonal fold-back O-1) are flagged, not claimed. One follow-up query (GUCY2C EAC tumor mRNA) could not be run through available tooling and is flagged as top priority rather than fabricated.