Prototyping GenoTHREAT a biosecurity solution for synthetic genomics

弗吉尼亚理工大学的弗吉尼亚生物信息学研究所获得了开发Genothreat的赠款，这是一种软件应用程序，用于筛选从基因合成公司订购的可能存在潜在有害序列的DNA序列。GenoTHREAT实施了卫生和人类服务部在一份题为“合成双链DNA提供者筛查框架指南”的文件中推荐的筛查算法。“重要的是要表征序列筛选算法的计算成本，错误标记的假阳性或无害序列的比率，以及假阴性或未被筛选算法检测到的关注序列的比率之间的关系。该屏幕被应用到一个数据库组成的混合物公开的合成DNA序列和注释的测试案例设计用于该项目。这种大规模的分析将导致最佳筛选参数的确定，这些参数代表了政府的安全考虑和基因合成公司的操作限制之间的可接受的折衷。克雷格·文特尔和他的团队最近发表了第一个合成细胞，这表明合成生物学取得了迅速进展，引起了公众、民选官员和各级政府对生物安全的关注。这笔拨款有助于采用联邦政府推荐的DNA筛选算法，以在基因合成公司的订单簿中检测是否存在需要进一步调查的令人担忧的序列。GenoTHREAT是利用该赠款开发的软件，将广泛提供（www.genothreat.org），以允许基因合成公司，合成DNA的用户或合成生物学的生物信息学资源管理人员实施政府建议的生物安全筛选。为了提供另一层生物安全保护，GenoTHREAT还将能够筛选DNA测序数据。正在与工业伙伴一起制定一项可持续性计划，该计划不涉及联邦为Genothreat的维护和未来发展提供资金。

The Virginia Bioinformatics Institute at Virginia Tech is awarded a grant to develop GenoTHREAT, a software application to screen DNA sequences ordered from gene synthesis companies for the possible presence of potentially harmful sequences. GenoTHREAT implements the screening algorithm recommended by the Department of Health and Human Services in a document entitled "Screening Frameworks Guidance for Synthetic Double-Stranded DNA Providers." It is important to characterize the relationship between the computational cost of the sequence screening algorithm, the rate of false positives or innocuous sequences that are incorrectly red flagged, and the rate of false negatives or sequences of concern not detected by the screening algorithm. The screen is applied to a database composed of a mixture of publicly available sets of synthetic DNA sequences and annotated test cases designed for this project. This large scale analysis will lead to the determination of optimal screen parameters that represent an acceptable compromise between the security concerns of the government and the operational constraints of gene synthesis companies. The rapid progress in synthetic biology demonstrated by the recent publication of the first synthetic cell by Craig Venter and his team has raised biosecurity concerns among the public, its elected officials, and various administrations. This grant facilitates the adoption of DNA screening algorithm recommended by the federal government to detect, in the order books of gene synthesis companies, the presence of sequences of concern requiring further investigations. GenoTHREAT, the software developed with the grant, will be made broadly available (www.genothreat.org) to allow gene synthesis companies, users of synthetic DNA, or managers of bioinformatics resources for synthetic biology to implement the biosecurity screen recommended by the government. In order to provide another layer of biosecurity protection, GenoTHREAT will also be capable of screening DNA sequencing data. A sustainability plan that does not involve federal funding for the maintenance and future development of GenoTHREAT is being developed with industrial partners.