Biology subjects

Foner, L.

Publications and source records attributed to Foner, L..

3 recordsLinked to original sources

bioRxiv2026

Developing a Standard Definition for Sequences of Concern

Readily available nucleic acid synthesis is both critical for the bioeconomy and an increasingly pressing security concern due to the potential for accidental or deliberate misuse. While biosecurity experts broadly agree that nucleic acid providers should screen orders for potential "sequences of concern," there has previously been no agreed standard for how to define and recognize such sequences. To address this gap, we first organized a test set of 1.1 million sequences from pathogens and toxins on the Australia Group Common Control Lists and their non-controlled relatives, along with model organisms and synthetic constructs. An initial categorization of sequences as to whether or not they were sequence of concern was produced by comparing the results of four biosecurity screening systems for each of these sequences, finding that these systems already agreed on the categorization of more than 80% of sequences. We then refined these results through a science-based stakeholder review process to define a rubric for determining whether a sequence should be flagged as a potential sequence of concern, then applied this rubric to improve the categorization of test sets. The result is a rubric that identifies sequences of concern with respect to human pandemic-potential viruses, key classes of low-risk genes, and controlled toxins. Applying this rubric to the test set collection has reduced the number of test sequences with disputed categorization by 44.3% for controlled viruses and 10.7% across the test set as a whole. Together, these results provide a concrete "sequence of concern" definition that can be used as a foundation for development of biosecurity screening standards and policy.

bioinformatics↗

bioRxiv2025

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

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.

bioinformatics↗

bioRxiv2024

Random adversarial threshold search enables automated DNA screening

Custom DNA synthesis underpins modern biology, but controlled genes in the wrong hands could threaten many lives and public trust in science. In .1992, a virology-trained mass murderer tried and failed to obtain physical samples of Ebola; today, viruses can be assembled from synthetic DNA fragments. Screening orders for controlled sequences is unreliable and expensive because current similarity search algorithms yield false alarms requiring expert human review. Exact-match search can achieve perfect specificity among short known sequences by detecting subsequences unique to controlled genes, but can be trivially evaded by incorporating mutations. Here we rescue exact-match search by additionally screening for predicted functional variants of pseudo-randomly chosen subsequences that arent found in known unregulated genes. To experimentally assess robustness, we protected nine windows from the M13 bacteriophage virus, then invited a "red team" to launch up to 21,000 attacks at each window and measure the fitness of their designed mutants. We identified defensible windows from regulated pathogens, built a test database that our experiments indicate will block 99.999% of functional attacks, and verified its sensitivity against redesigned enzymes. Exact-match search with functional variant prediction offers a promising way to safeguard biotechnology by automating DNA synthesis screening. SummarySearching for exact matches to pre-computed functional variants unique to controlled genes enables sensitive, secure, and automated DNA synthesis screening.

synthetic biology↗