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 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.

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