CRC-Screen: Certified DNA-Synthesis Hazard Screening Under Taxonomic Shift
For DNA-synthesis providers, this work addresses the critical problem of screening hazardous sequences under taxonomic shift, demonstrating that calibration data, not algorithms, is the binding constraint.
The paper shows that standard DNA-synthesis hazard screening fails under taxonomic shift (100% false-flag rate) and proposes a calibrated screener using three signals fused via conformal risk control, achieving 0% test miss rate and 0% false-flag rate on 9/10 folds at α=0.05.
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 $\mathbb{E}[\mathrm{FNR}] \le α$. Across ten leave-one-taxonomic-family-out folds at $α=0.05$ on UniProt KW-0800 reviewed toxins, the calibrated screener achieves 0% 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 $α=10^{-3}$ 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