Building resilience in nucleic acid screening systems against split orders by integrating assembly pipelines into screening systems and validating resilience through test sets
Endorsements made here support IBBIS (International Biosecurity and Biosafety Initiative for Science).
Building resilience in nucleic acid screening systems against split orders by integrating assembly pipelines into screening systems and validating resilience through test sets
Endorsements made here support IBBIS (International Biosecurity and Biosafety Initiative for Science).
Project Details
Updated 07/20/26 · Edited by orgBackground
There is increasing concern and risk that threat actors will attempt to evade nucleic acid synthesis screening tools by splitting orders for sequences of concern (SOCs) into short oligos and assembling those fragments in vitro. It is thus a priority to test for resilience from split-order attempts and subsequently build resilience within screening systems against such threats by being able to detect SOCs from oligo pools.
Project
The first part of the project will involve collectively developing high-quality assembly test sets, utilizing the Sequence Biosecurity Risk Consortium (SBRC) test sets of full fragments to select high-consequence SOCs while taking into account various assembly methods. The second part of the project will involve building pipelines within IBBIS’ common mechanism (commec) screening tool to detect split orders and pass the test sets.
Consultants with relevant experience will be working on this project, overseen by me and another lead, within the umbrella of the SBRC, a consortium moderated by me and two other leads. The deliverables developed are listed below, and there will be regular SBRC working group meetings also overseen by senior members of the SBRC as well as a senior bioinformatician working on commec.
Deliverables
Deliverable 1: Working group meetings will be setup and consultants will attend weekly split-order working group meetings with other SBRC members who are working on developing test sets to devise methodologies and plans of action to develop assembly test sets.
Deliverable 2: Collectively develop and iterate to create high-quality split-order test sets from SOCs within the SBRC test set and benign sequences, taking into account various assembly methods (at least 3 among a prioritised set of assembly methods, including some Gibson, Golden Gate, Sidewinder, polymerase cycling assembly, Darwin) and high-consequence SOCs.
Deliverable 3: Draft a short report on the outputs and methods used by the working group.
Deliverable 4: Build an efficient pipeline (<1 min / pool) to assemble oligo pools. Share code within the SBRC and integrate within commec, passing the constructed test sets (>95% recall), while avoiding increasing false positives, to build resilience against assembly threats.
Theory of Impact
Updated 07/20/26 · By grantmaking.aiAI-enabled biodesign tools and frontier models are now increasingly capable of designing short oligos from a whole gene that users can order from a synthesis provider and subsequently assemble in vitro. Such short oligos are currently difficult to detect by current screening tools, making them prone to evasion if someone intends to assemble a sequence of concern.
This exacerbates biosecurity risk from a malicious actor being more easily able to order short oligos to assemble sequences of concern from pathogens of pandemic potential from such fragments.
This project will ensure that screening tools have robust test sets that they can evaluate against to ensure they can detect potential assembly attempts from short oligos and provide a proof of concept for resilience by building a pipeline in our own screening tool that can detect assembly attempts through split orders.
People
Updated 07/08/26 · Edited by orgTeam Member
Technical Lead
I'm one of the people on this project ― just want to share that I think nailing the easy case of split orders (short oligos in a single customer order, intended for assembly) is a necessary prerequisite for handling the harder case (deliberate splitting of orders across time or vendors). We already have a pretty good group of people working on this at the SBRC in a primarily-volunteer capacity, but we could accelerate this with some funding!
You can learn more about the SBRC's work in this talk I gave last week on defining sequences of concern: https://www.youtube.com/watch?v=DBJzI-\_uiBc&t=1h4m
The SBRC is mentioned as a core effort in this IFP Launch Sequence piece on Securing the DNA Supply Chain, which also references handling of short oligos as a key unsolved problem:
> The second unsolved problem is short oligonucleotides — oligos — that can be assembled into longer sequences. As techniques for oligo assembly improve, biosecurity relying exclusively on screening entire genes will become increasingly untenable. Two things make oligo screening hard: 1. The market is more decentralized, with up to five times as many manufacturers of short oligos as gene-length DNA, so more providers have to implement screening. 2. Short fragments carry less signal compared to full genes: it’s harder to tell whether any single oligo is dangerous, or whether multiple orders split across different providers could be assembled into something that is.