ParadoxMap
I set out to test whether the IL-23/IL-17 therapeutic paradox — the same pathway helping in one organ and harming in another — has a measurable tissue-intrinsic signature in public single-cell atlases, using a preregiste
Core trick
Computes tissue-level IL23R/IL12RB1 receptivity and IL17RA/IL17RC protective-receiver scores from single-cell atlases under a frozen, preregistered spec.
Description
I set out to test whether the IL-23/IL-17 therapeutic paradox — the same pathway helping in one organ and harming in another — has a measurable tissue-intrinsic signature in public single-cell atlases, using a preregistered, blinded framework across gut, psoriatic skin, and HS.
The scientific result is honest and bounded: the cross-tissue comparison is not computable from current public data — psoriasis and HS are absent from the public single-cell disease vocabulary entirely — and the within-tissue P comparison is underpowered rather than null. What survives is reference-free and real: a large IL23R-negative effector reserve, and tissue-specific co-activation (gut IL-23+IL-1, skin IL-23+TCR).
The deeper output is methodological. Working with Claude Science, I logged nine data-integrity defects, none caught by any automated check — each one about what a number counts, not whether it computes. Deciding what is true, it turns out, is still the human's job. That discipline is the transferable result.
ValerieTse/ParadoxMap_ClaudeScienceHackathon★ 00 forksPythonCreated Jul 13, 2026 · last push Jul 13, 2026
README excerpt
# IL-23/IL-17 tissue-intrinsic E/D/P framework Reference-free, frozen-preregistered single-cell analysis of the IL-23→IL-17 therapeutic paradox across three inflamed human tissues (ulcerative-colitis gut, lesional psoriatic skin, lesional hidradenitis suppurativa). Three per-tissue quantities are computed under a frozen specification, with no disease-outcome label and no optimisation toward any expected direction: - **E** — effector dependence (IL-17 output induced vs constitutive) - **D** — IL-23 receptivity of IL-17 producers (`IL23R + IL12RB1` only) - **P** — protective-receiver burden, `√(mean(IL17RA)·mean(IL17RC))` on lesional epithelium ## Repository layout | Folder | Contents | |---|---| | `related_paper/` | `REFERENCES.md` — source atlases + reference datasets, verified DOIs/PMIDs/accessions | | `scripts/` | Analysis scripts (ingest, cell-calling, annotation, D/P computation, benchmarks) | | `results/` | All computed outputs — see sub-tree below | | `manuscript/` | `MANUSCRIPT_v2.md` (publishable draft, all 12 citations PubMed-verified) + `MANUSCRIPT.md` (prior working draft) + `figures/` | | `talk/` | 3-minute talk: `EDP_3min.pptx` (6 slides, embeds Fig 1, 2, 4, 5; Fig 3 P-power omitted for the 3-min cut), `EDP_3min_deck.md` (portable mirror), `SPEECH_3min.md` (timed speech + Q&A primer) | | `README.md` | This file | ### `results/` sub-tree - `results/tables/` — CSV/JSON deliverables (pseudobulk-derived tables, P by path, bootstrap, QC/discard/depth, positive co