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Objective: 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. Methodology: Construction of the prototype test dataset involved four tool developers screening nucleic acid sequences from three taxonomic clusters of controlled organisms (Orbivirus, Francisella tularensis, and Coccidioides). Results were mapped onto predefined, comparable categories, checking for consensus or conflicts. Conflicts were grouped based on gene annotation and resolved through discussion. Results: 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. Conclusions and Next Steps: 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. [ABSTRACT FROM AUTHOR]

Objective: 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., Methodology: Construction of the prototype test dataset involved four tool developers screening nucleic acid sequences from three taxonomic clusters of controlled organisms ( Orbivirus , Francisella tularensis , and Coccidioides ). Results were mapped onto predefined, comparable categories, checking for consensus or conflicts. Conflicts were grouped based on gene annotation and resolved through discussion., Results: 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., Conclusions and Next Steps: 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., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Background: In the wake of the SARS-CoV-2 pandemic, scientists have scrambled to collect and analyze SARS-CoV-2 genomic data to inform public health responses to COVID-19 in real time. Open source phylogenetic and data visualization platforms for monitoring SARS-CoV-2 genomic epidemiology have rapidly gained popularity for their ability to illuminate spatial-temporal transmission patterns worldwide. However, the utility of such tools to inform public health decision-making for COVID-19 in real time remains to be explored., Objective: The aim of this study is to convene experts in public health, infectious diseases, virology, and bioinformatics-many of whom were actively engaged in the COVID-19 response-to discuss and report on the application of phylodynamic tools to inform pandemic responses., Methods: In total, 4 focus groups (FGs) occurred between June 2020 and June 2021, covering both the pre- and postvariant strain emergence and vaccination eras of the ongoing COVID-19 crisis. Participants included national and international academic and government researchers, clinicians, public health practitioners, and other stakeholders recruited through purposive and convenience sampling by the study team. Open-ended questions were developed to prompt discussion. FGs I and II concentrated on phylodynamics for the public health practitioner, while FGs III and IV discussed the methodological nuances of phylodynamic inference. Two FGs per topic area to increase data saturation. An iterative, thematic qualitative framework was used for data analysis., Results: We invited 41 experts to the FGs, and 23 (56%) agreed to participate. Across all the FG sessions, 15 (65%) of the participants were female, 17 (74%) were White, and 5 (22%) were Black. Participants were described as molecular epidemiologists (MEs; n=9, 39%), clinician-researchers (n=3, 13%), infectious disease experts (IDs; n=4, 17%), and public health professionals at the local (PHs; n=4, 17%), state (n=2, 9%), and federal (n=1, 4%) levels. They represented multiple countries in Europe, the United States, and the Caribbean. Nine major themes arose from the discussions: (1) translational/implementation science, (2) precision public health, (3) fundamental unknowns, (4) proper scientific communication, (5) methods of epidemiological investigation, (6) sampling bias, (7) interoperability standards, (8) academic/public health partnerships, and (9) resources. Collectively, participants felt that successful uptake of phylodynamic tools to inform the public health response relies on the strength of academic and public health partnerships. They called for interoperability standards in sequence data sharing, urged careful reporting to prevent misinterpretations, imagined that public health responses could be tailored to specific variants, and cited resource issues that would need to be addressed by policy makers in future outbreaks., Conclusions: This study is the first to detail the viewpoints of public health practitioners and molecular epidemiology experts on the use of viral genomic data to inform the response to the COVID-19 pandemic. The data gathered during this study provide important information from experts to help streamline the functionality and use of phylodynamic tools for pandemic responses., (©Shannan N Rich, Veronica Richards, Carla Mavian, Brittany Rife Magalis, Nathan Grubaugh, Sonja A Rasmussen, Simon Dellicour, Bram Vrancken, Christine Carrington, Rebecca Fisk-Hoffman, Demi Danso-Odei, Daniel Chacreton, Jerne Shapiro, Marie Nancy Seraphin, Crystal Hepp, Allison Black, Ann Dennis, Nídia Sequeira Trovão, Anne-Mieke Vandamme, Angela Rasmussen, Michael Lauzardo, Natalie Dean, Marco Salemi, Mattia Prosperi. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.04.2023.)

Summary: TARDiS is a novel phylogenetic tool for optimal genetic subsampling. It optimizes both genetic diversity and temporal distribution through a genetic algorithm., Availability and Implementation: TARDiS, along with example datasets and a user manual, is available at https://github.com/smarini/tardis-phylogenetics., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)