Wheeler Nicole E, Bartling Craig, Carter Sarah R, Clore Adam, Diggans James, Flyangolts Kevin, Gemler Bryan T, Rife Magalis Brittany, Beal Jacob
Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
Battelle Memorial Institute, Columbus, Ohio, USA.
Appl Biosaf. 2024 Sep 18;29(3):133-141. doi: 10.1089/apb.2023.0033. eCollection 2024 Sep.
DNA synthesis companies screen orders to detect controlled sequences with misuse risks. Assessing screening accuracy is challenging owing to the breadth of biological risks and ambiguities in risk definitions. Here, we detail an International Gene Synthesis Consortium working group's rationale and process to develop a prototype DNA synthesis screening test dataset, aiming to establish a baseline of screening system accuracy to compare with various screening approaches.
Construction of the prototype test dataset involved four tool developers screening nucleic acid sequences from three taxonomic clusters of controlled organisms (, , and ). Results were mapped onto predefined, comparable categories, checking for consensus or conflicts. Conflicts were grouped based on gene annotation and resolved through discussion.
The process highlighted several long-standing challenges in DNA synthesis screening, including the qualitative differences in approaches taken by screening tools. Our findings highlight the lack of clarity in assessing pathogen sequences with respect to regulatory control language, compounded by scientific uncertainty. We illustrate the current degree of consensus and existing challenges using classification statistics and specific examples.
This prototype underscores the necessity of expert-regulator coordination in assessing gene-associated risks, offering a template for creating test sets across all taxonomic groups on international control lists. Expanding the working group would enrich dataset comprehensiveness, enabling a transition from species-focused to function-focused regulatory controls. This sets the foundation for quality control, certification, and improved risk assessment in DNA synthesis screening.
DNA合成公司会对订单进行筛查，以检测存在滥用风险的受控序列。由于生物风险的广度和风险定义的模糊性，评估筛查准确性具有挑战性。在此，我们详细介绍国际基因合成联盟一个工作组开发DNA合成筛查测试数据集原型的基本原理和过程，旨在建立筛查系统准确性的基线，以便与各种筛查方法进行比较。
原型测试数据集的构建涉及四位工具开发者对来自三类受控生物（、和）分类群的核酸序列进行筛查。结果被映射到预定义的、可比较的类别上，检查是否存在共识或冲突。冲突根据基因注释进行分组，并通过讨论解决。
该过程凸显了DNA合成筛查中几个长期存在的挑战，包括筛查工具所采用方法的质的差异。我们的研究结果凸显了在根据监管控制语言评估病原体序列方面缺乏清晰度，科学不确定性又加剧了这一问题。我们使用分类统计和具体例子来说明当前的共识程度和现有挑战。
这个原型强调了专家与监管机构在评估基因相关风险方面进行协调的必要性，为在国际控制清单上针对所有分类群创建测试集提供了一个模板。扩大工作组将丰富数据集的全面性，使监管控制从以物种为重点转向以功能为重点。这为DNA合成筛查中的质量控制、认证和改进风险评估奠定了基础。
