PNNL

Historically, the biodefense community relies on lists of known agents—pathogens and biotoxins like anthrax and ricin—that have been identified and prioritized as threats. In Health Security, a team of researchers at Pacific Northwest National Laboratory (PNNL) and the University of Texas at El Paso (UTEP) discuss the computational challenges of thinking beyond the list and developing bioagent-agnostic signatures to assess threats.

“As biological threats evolve, we face more unknowns and an increased sense of urgency to quickly detect and characterize disease agents to increase our biopreparedness and drive rapid responses. By shifting from an identification-based approach to a characterization-based one—with the right computational and data capabilities—we can accurately and reproducibly assess impacts without prior knowledge of an agent,” said Andy Lin, data scientist at PNNL.

The article “Computational and Systems Biology Advances to Enable Bioagent Agnostic Signatures” explores the computational data challenges of threat-agnostic biodefense, or the ability to characterize an unknown agent’s likely impact to human, animal, and plant health. The researchers discuss how the biodefense community can make the shift to a dual list-based and bioagent-agnostic signatures approach—but it will not be without its challenges. The shift will require policy changes, technological improvements, and improved data analytics.

The research brought together PNNL’s Lin, Errett Hobbs, Karen Taylor, Tony Chiang, and Jay Bardhan, with UTEP’s Cameron Torres, Stephen Aley, and Charles Spencer—convening diverse expertise across data science, computational systems biology, cytometry, immunology, and more. The research showcases the power of a cross-institution collaboration building on PNNL and UTEP’s long-standing partnership and joint appointment program to accelerate the science mission of both institutions. The UTEP team performed experiments that helped demonstrate the challenges discussed in the paper. 

The research also builds on PNNL’s previous effort, highlighted in a 2021 Pathogens publication, “Beyond the List: Bioagent-Agnostic Signatures Could Enable a More Flexible and Resilient Biodefense Posture Than an Approach Based on Priority Agent Lists Alone,” which addressed how traditional list-based approaches are ill-equipped to accommodate threats posed by emergent, reemergent, or novel pathogens. A threat-agnostic model could present a means to more effectively surveil for and treat known and novel agents alike.

“While the biodefense community may have only just begun to develop technologies for a threat-agnostic approach, we’re highlighting promising new immunological approaches and the data challenges that need to be overcome to build exciting new possible paths forward,” said Lin.

The article was published in the March 2024 issue of Health Security and featured in the March 17 issue of the Global Biodefense headlines.