Adversary Resilient Synthetic Gene Order Screening
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Solution Overview
Problem
Current screening methods for synthetic DNA sequences are insufficient to detect sequences of concern (SOCs) that are hidden through genetic obfuscation, where SOC fragments are split and interleaved with legitimate DNA sequences, making it difficult to identify and reconstruct the obfuscated DNA.
Innovation Solution
A system and method for adversary resilient screening that involves applying a first alignment algorithm to generate local alignments, removing the k largest alignment gaps to produce a clean query sequence, and then applying a second alignment algorithm to generate a clean alignment score, which includes a gap removal penalty to account for the probability of successful reconstruction of SOC fragments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional sequence alignment tools (BLAST) are used to screen DNA orders, then screening speed and simplicity are improved, but detection precision of obfuscated SOCs deteriorates
Solution Approach 1:
The patent segments the screening process into multiple stages: initial fast screening with BLAST, followed by gap analysis to identify potential obfuscation patterns, and finally detailed reconstruction analysis. This multi-stage segmentation allows the system to maintain high throughput for obvious cases while applying more sophisticated analysis only when needed, thus resolving the contradiction between screening speed and detection precision.
Solution Approach 2:
The patent performs preliminary gap analysis on alignment results before full reconstruction attempts. By examining the gap patterns in preliminary alignments and identifying characteristics consistent with obfuscation (such as regular spacing, specific gap lengths), the system can flag potential obfuscated sequences for further analysis, improving detection precision without compromising overall screening efficiency.
2Measurement precision
If gap removal penalty is increased to account for reconstruction difficulty, then detection accuracy of obfuscated sequences is improved, but false positive rate increases
Solution Approach 1:
The patent dynamically adjusts the gap removal penalty parameter based on multiple factors including gap length, gap spacing patterns, and local sequence composition. Rather than using a fixed high penalty that would cause false positives, the system modifies the penalty parameter adaptively: applying higher penalties only when gap patterns strongly suggest intentional obfuscation, and lower or zero penalties when gaps appear to be natural biological variations, thus improving detection accuracy while controlling false positive rates.
Solution Approach 2:
The system incorporates feedback mechanisms where initial screening results inform subsequent analysis parameters. When BLAST alignments show unexpected gap patterns, the system feeds this information back to adjust the gap removal penalty and trigger more rigorous reconstruction analysis. Conversely, when alignments show typical biological variation patterns, the system reduces the penalty and avoids unnecessary false alarms, thereby balancing detection accuracy with false positive control.
Data Source
AI summary
A system and methods for adversary resilient screening of synthetic gene orders, include: applying a first alignment algorithm to generate multiple local alignments of a query sequence with a target sequence, wherein each local alignment aligns a substring of the query sequence to a substring of the target sequence to maximize an alignment score; determining unaligned sections of the query sequence to be alignment gaps; and removing k largest alignment gaps of the query sequence to generate a clean query sequence.