An improved virome-capture-sequencing method for viral diagnosis and virus discovery

This technology is an improved, redesigned virome-capture sequencing platform for vertebrate viruses that increases the sensitivity of sequence-based virus detection and characterization while reducing the number of probes and synthesis costs.

Unmet Need: Improved viral capture for high-throughput sequencing

High-throughput nucleic acid sequencing has become an important tool for detecting and differentiating viral infections in research and clinical laboratories. However, viral nucleic acids are often present at very low abundance relative to host material, making direct sequencing inefficient and costly. Conventional enrichment approaches, including filtration, nuclease treatment, and rRNA depletion, often lack sufficient sensitivity for reliable detection of low-abundance or divergent viruses. There is a need for improved methods that increase the sensitivity and efficiency of viral detection to enable broader implementation of sequencing-based diagnostics and surveillance.

The Technology: Optimized probe-based viral capture system

This technology is an improved virome-capture sequencing platform that uses a redesigned biotinylated oligonucleotide probe library for solution-based hybrid capture of viral nucleic acids prior to high-throughput sequencing. The updated probe set spans all known vertebrate virus taxa, reduces the total number of probes, corrects sequence errors present in earlier versions, and adds probes for newly identified viral sequences. The use of longer probes spaced farther apart may improve capture of more distantly related viruses.

Experimental data demonstrate a 1,000–10,000-fold increase in viral reads from diverse clinical and environmental sample types compared to conventional Illumina sequencing.

Applications:

• Clinical viral diagnostics
• Infectious disease surveillance
• Emerging virus discovery

Advantages:

• Reduced probe count and synthesis cost
• Improved viral taxonomic coverage
• Expanded detection of newly identified viruses
• Enhanced capture of divergent viral sequences
• Integrated External RNA Controls Consortium (ERCC) enrichment controls
• Increased viral read recovery

Lead Inventor:

Thomas Briese, Ph.D.

Patent Information:

Patent Issued (US 10,815,536)

Related Publications:

• Briese T, Kapoor A, Mishra N, Jain K, Kumar A, Jabado OJ, Lipkin WI. “Virome Capture Sequencing Enables Sensitive Viral Diagnosis and Comprehensive Virome Analysis.” mBio. 2015;6(5):e01491-15.

• Kapoor V, Briese T, Ranjan A, Donovan WM, Mansukhani MM, Chowdhary R, Lipkin WI. “Validation of the VirCapSeq-VERT system for differential diagnosis, detection, and surveillance of viral infections.” J Clin Microbiol. 2024 Jan 17;62(1):e0061223.

• McGill F, Tokarz R, Thomson EC, Filipe A, Sameroff S, Jain K, Bhuva N, Ashraf S, Lipkin WI, Corless C, Pattabiraman C, Gibney B, Griffiths MJ, Geretti AM, Michael BD, Beeching NJ, McKee D, Hart IJ, Mutton K, Jung A, Miller A, Solomon T. “Viral capture sequencing detects unexpected viruses in the cerebrospinal fluid of adults with meningitis.” J Infect. 2022 Apr;84(4):499-510.

Tech Ventures Reference:

• Licensing Contact: Kristin Neuman