# Held-out evidence resolves follow-up measurement decisions in biological screens

arXiv: https://arxiv.org/abs/2607.27651 · HTML: https://mlsanity.com/paper/2607.27651/

## Key facts

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- First posted on arXiv 30 Jul 2026.

## Abstract (arXiv)

Machine learning determines which follow-up measurements biological screens collect. In a six-rule Cell Painting battery, the highest-value rule would re-image 96.01% of the library and had a 97.14% false-activation upper bound, showing why predicted value alone cannot justify replacing a fixed plan. We developed OPAL, a held-out decision test that freezes a rule and judges unnecessary measurement, coverage and value after cost against archive-specific criteria fixed before final evaluation. A development-selected sparse Cell Painting rule had 18.2-fold lower added-well burden, but its false-discovery bound exceeded 35%, so the fixed plan remained. LINCS--LJP favored broad acquisition under point-estimate criteria set during development, not selective saving. CTRP required fallback because its frozen score missed measured opportunity. OPAL separates optimization from evidence sufficient to change an experiment.