ThreatSEQ™ DNA Screening Web Service

The ThreatSEQ DNA screening service offers gene synthesis companies an alternative to the current semi-manual and subjective DNA screening options, empowering them to make faster, better decisions to protect themselves, their clients and society from potential biosecurity risks while keeping costs manageable. 

The technology enables:

• Higher confidence levels: greatly reduces error rates and provides objective assessment of threat levels.
• Fewer false positives: reduces false positives 70-90 percent compared to current screening methods.
• Reduced labor costs: fewer false positives in conjunction with automatically provided sequence-specific threat information reduce required investigation time for potential threats. 

Our technology is based on threat identification algorithms built around Battelle’s proprietary virulence factors database containing genetic sequences of concern. Because the database is organized around specific sequences rather than matching against the full genomes of known pathogens, the algorithm can identify the specific sequence in question and inform biosecurity staff through comprehensive, automated reporting and assignment of threat status.

Virulence Factors Database 
The database was built on more than a decade of research into the factors that make pathogens dangerous. It compiles more than 10,000 sequences of concern comprising 850 types of sequences of concern from 75 species of bacteria, 96 viruses, 12 eukaryotic pathogens and other contributors to pathogens. 

These factors include (but are not limited to):  

• Virulence factors
• Antibiotic resistance
• Immune evasion factors
• Human bioregulators
• Protein toxins
• Other threat factors (e.g., opioid enzyme pathways)

The database covers 100 percent of U.S. Select Agents and Australia Group Lists (Tier 1) and virtually all known bacterial human/zoonotic agents. To ensure the most comprehensive comparison is performed, the user is also provided with results against the full genomes of organisms derived from the National Center for Biotechnology Information (NCBI) database and other select agent registries around the world. 



Threat Identification Algorithm

The algorithm rapidly scans a requested DNA sequence and looks for matches within the threat factors database. Matches may be entire gene sequences or parts of gene sequences. Our ThreatSEQ web service has been designed to operate efficiently and to detect complex patterns (e.g., tiled mosaic DNA fragments).

In addition to identifying positive matches, our algorithm provides information about the types of threats that a gene sequence may present by analyzing the structures of the genes and their resulting functions. The existing analysis is supported by more than 4,400 full-text peer reviewed papers, and Battelle continues to update the database and algorithm as new research emerges.
 
Threat Reporting 
Battelle's ThreatSEQ solution provides easy-to-understand reports that flag the specific sequences of concern and characterize the potential hazard associated with the sequence. The reports allow reviewers to easily determine the threat level presented by the requested sequence and understand the rationale behind the threat determination.  

Reviewers can run reports of order history and threat status for easy tracking and auditing of screening results.

Threats are ranked for more efficient review. 

• Threat = matches a known sequence of concern
• Potential threat = matches any sequence in a non-annotated select agent's genome
• Unlikely threat = matches a non-concerning sequence in an annotated select agent's genome
• Non-threat = matches a sequence in a non-select agent's genome

As the synthetic biology industry matures and the technology becomes more powerful and affordable, biosecurity risks are growing. Existing solutions provide limited resolution and present a growing cost burden, largely driven by manual review of false positive screening hits. 

The ThreatSEQ DNA screen service empowers gene synthesis companies to make faster, more informed decisions to protect themselves, their clients and society from potential biosecurity risks. The software and analysis service provides rapid analysis of DNA sequences submitted for production to identify potential DNA sequences of concern prior to fulfilling gene synthesis requests. 

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