Studying pathogens degrades BLAST-based pathogen identification

Area of Science:

• Synthetic biology
• Biosecurity
• Bioinformatics

Background:

• Accurate biosecurity assessments of genetic sequences are crucial as synthetic biology advances.
• Current methods often rely on BLAST searches against general databases like NCBI, which were not designed for biosafety.
• Taxonomic errors in databases can lead to misclassifications.

Purpose of the Study:

• To evaluate the accuracy of BLAST for biosecurity determinations.
• To identify limitations of using general databases for classifying genetic sequences.
• To highlight the implications of false positives in biosecurity decision-making.

Main Methods:

• Analysis of BLAST algorithm performance against NCBI nucleic acid and protein databases.
• Focus on false positive rates in taxonomic categorization.
• Examination of commonly used biotechnology tool sequences.

Main Results:

• BLAST searches against NCBI's protein database can incorrectly categorize common biotechnology tool sequences as pathogens or toxins.
• These errors are more prevalent for widely used tools and high-interest pathogens.
• Taxonomic ambiguities in databases contribute significantly to misclassifications.

Conclusions:

• Current biosecurity tools relying on BLAST against general databases are prone to errors.
• The problem is exacerbated for critical pathogens and widely used biotechnologies.
• There is a critical need to develop new, specialized methods for biosafety determinations in synthetic biology.