CRC-Screen: Certified DNA-Synthesis Hazard Screening Under Taxonomic Shift

Najmul Hasan

Keywords: DNA-Synthesis Hazard Screening Under Taxonomic Shift

TL;DR: Calibration data, not algorithms, bounds certified DNA-synthesis screening: a three-signal screener calibrated by Conformal Risk Control achieves 0% miss on every fold and 0% false-flag on 9/10 leave-one-family-out folds at α=0.05.

Abstract: DNA-synthesis providers screen incoming orders by searching the requested sequence against curated hazard lists. We show that this baseline collapses to a 100% false-flag rate when the hazardous sequence comes from a taxonomic family absent from the reference set: under Conformal Risk Control's certified miss-rate constraint, a low-discrimination signal forces the threshold below the entire test-benign mass. We compose three signals derived from a synthesis order's public annotation: $k$-mer Jaccard similarity to known toxins, the trimmed-mean score of a five-LLM judge panel, and cosine similarity to clustered embedding centroids. Fused under a monotone logistic aggregator and calibrated by Conformal Risk Control, the resulting screener certifies $\mathbb{E}[\mathrm{FNR}] \le \alpha + \mathrm{TV}$, where the additive term is the calibration-to-test distribution shift under family holdout (a certified ceiling of 24–49% across folds). Across ten leave-one-taxonomic-family-out folds at $\alpha=0.05$ on UniProt KW-0800 reviewed toxins, the calibrated screener achieves 0% *empirical* test miss rate on every fold and 0% test false-flag rate on nine of ten folds. The bound's finite-sample slack $1/(n_\mathrm{cal}+1)$ caps the certifiable miss rate at 1.77% on our 200-hazard subsample; reaching procurement-grade $\alpha=10^{-3}$ requires an $18\times$ larger calibration set, which the full reviewed UniProt KW-0800 corpus is large enough to deliver. The binding constraint on certifiable DNA-synthesis screening is calibration data, not algorithms. *Code:* https://github.com/najmulhasan-code/crc-screen

Track: Track 2: ML Research by Muslim Authors

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Submission Number: 65