New Preprint: Inter-Tool Analysis of a NIST Dataset for Assessing Baseline Nucleic Acid Sequence Screening

Green background image of DNA helix. Text reads An Evaluation of Biothreat Screening Tools

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.

Read the full preprint here.


Authors:

Tyler S. Laird1, Kevin Flyangolts2, Craig Bartling3, Bryan T. Gemler3, Jacob Beal4, Tom Mitchell4, Steven T. Murphy4, Jens Berlips5, Leonard Foner5, Ryan Doughty6, Felix Quintana6, Michael Nute6, Todd J. Treangen7,8, Gene Godbold9, Krista Ternus10, Tessa Alexanian11, Nicole Wheeler12, Samuel P. Forry1

1NIST, 100 Bureau Dr. Gaithersburg, MD 20899
2Aclid, 442 5th Ave #2300 New York, NY 10018
3Battelle Memorial Institute, 505 King Ave, Columbus OH 43201
4RTX BBN Technologies, 10 Moulton Street, Cambridge, MA 02138
5SecureDNA Foundation, Aeschenplatz 6, Basel, Switzerland 4010
6Department of Computer Science, Rice University, Houston, TX 77005
7Department of Bioengineering, Rice University, Houston, TX 77005
8Ken Kennedy Institute, Rice University, Houston, TX 77005
9Signature Science, LLC; 1670 Discovery Drive, Charlottesville VA 22911 USA
10Signature Science, LLC; 8501 North Mopac Expressway, Suite 100, Austin, TX 78759
USA
11International Biosecurity and Biosafety Initiative for Science (IBBIS), Geneva,
Switzerland
12Institute of Microbiology and Infection, University of Birmingham, UK