A Sensitivity Study for Interpreting Nucleic Acid Sequence Screening Regulatory and Guidance Documentation: Toward a...

Area of Science:

• Bioinformatics
• Biosecurity
• Molecular Biology

Background:

• Regulatory and guidance documentation for synthetic nucleic acids can be ambiguous.
• Screening of nucleic acid orders is crucial for biosafety and biosecurity.
• Existing frameworks may not fully address the nuances of synthetic sequence control.

Purpose of the Study:

• To develop an objective nucleic acid sequence screening framework.
• To conduct an empirical sensitivity study on the impact of documentation ambiguities.
• To assess the control of synthetic nucleic acids and screening of nucleic acid orders.

Main Methods:

• Constructed foundational risk levels using the UltraSEQ bioinformatic sequencing screening tool.
• Defined risk levels from high (regulated) to low (non-regulated concern) to no-risk.
• Analyzed a dataset of 141,651 synthetic sequences and evaluated parameter impacts on UltraSEQ.

Main Results:

• No-risk sequences constituted 90-92% of the dataset.
• Non-regulated sequences of concern represented 7-9% of sequences, irrespective of parameter changes.
• Minimum hit homology level had the greatest impact on flagged sequences, followed by region length and uniqueness.

Conclusions:

• The study enhances understanding for gene synthesis providers and biosafety professionals regarding regulatory interpretations.
• The developed risk level framework supports evolving nucleic acid sequence screening needs.
• Further development is required for tools connecting sequence and order predictions for contextual risk assessment.