Inter-tool analysis of a NIST dataset for assessing baseline nucleic acid sequence screening

Published

June 18, 2025

Author(s)

Tyler Laird, Samuel Forry, Kevin Flyangolts, Craig Bartling, Bryan Gemler, Jacob Beal, Tessa Alexanian, Nicole Wheeler, Krista Ternus, Todd Treangen, Gene D. Godbold, Michael Nute, Leonard Foner, Scott Jackson, Jens Berlips

Abstract

Nucleic acid synthesis is a dual-use technology that can benefit fields such as biology, medicine, and information storage. However, synthetic nucleic acids could also potentially be used negligently and ultimately cause harm, or be used with malicious intent to cause harm. Thus, this technology needs to be appropriately safeguarded. Sequence screening is one component of a biosecurity protocol for preventing such harm and consists of differentiating Sequences of Concern (SOCs) from benign sequences that are not associated with pathogenicity or toxicity. There exist many fit-for-purpose tools that have been developed for DNA synthesis sequence screening. However, questions remain regarding their performance with respect to consistency of screening. To aid in determining if screening tools are harmonized in regard to baseline sequence screening, NIST constructed a test dataset based on current screening recommendations. NIST then sent blinded datasets to sequence screening tool developers for testing. Overall, there was a general agreement between the tools and NIST assignments of the sequences and all tools had a baseline performance of greater than 95% sensitivity and 97% accuracy. Disagreement on specific sequences largely arose from single tools and could be traced to differences in defining a SOC and/or methodological differences in screening algorithms.

Citation

(potentially a different journal, still TBD)

Pub Type

Journals

Keywords

Nucleic acid synthesis, sequence screening, DNA screening, biosecurity

Citation

Laird, T. , Forry, S. , Flyangolts, K. , Bartling, C. , Gemler, B. , Beal, J. , Alexanian, T. , Wheeler, N. , Ternus, K. , Treangen, T. , Godbold, G. , Nute, M. , Foner, L. , Jackson, S. and Berlips, J. (2025), Inter-tool analysis of a NIST dataset for assessing baseline nucleic acid sequence screening, (potentially a different journal, still TBD) (Accessed June 21, 2025)