Nucleic Acid Observatory

Evaluating biosurveillance approaches

Understanding and comparing different approaches to large-scale disease monitoring

A multi-pronged approach to evaluating biosurveillance methods

Biosurveillance encompasses a wide array of approaches for detecting new disease outbreaks. Proposed strategies include sampling municipal wastewater, aggregated airplane waste, air filters from planes or HVAC systems, swabs or saliva samples from various human populations, and a wide array of clinical samples that could be repurposed for disease monitoring. All of these approaches have important advantages and disadvantages; for the NAO, the challenge is to identify which are the most sensitive, reliable, and cost-effective from the perspective of pathogen-agnostic early warning.

To obtain a deeper and more quantitative understanding of their relative merits, NAO researchers are using a combination of epidemiological modeling, analysis of existing data, and experimentation to characterize different biosurveillance approaches. By building partnerships with local government agencies, research groups and companies interested in building better disease surveillance, and combining their insights and experience with the NAO’s in-house research, our goal is to build a comprehensive understanding of how to deploy limited resources to achieve the most effective & reliable early warning system.

Municipal versus airplane wastewater

So far, the NAO has primarily focused on metagenomic sequencing of human wastewater as a strategy for pathogen-agnostic threat detection, due to its logistical advantages and established ability to detect a wide variety of human pathogens. We are currently investigating several wastewater-based monitoring approaches, including solid & liquid samples from municipal treatment plants and aggregated lavatory waste from airplanes, to better characterize their properties and suitability for our biosurveillance goals.

Investigating pooled swab samples

While we continue to view human wastewater as a promising sampling option, we think pooled nasal swabs have the potential to offer better sensitivity for the same cost, due to the substantially higher relative abundance of respiratory pathogens. However, there remain major open questions with the details of this approach, including around cost, logistics, and sample preparation. We've started a pilot collection program to explore these questions and refine our approach.

Nucleic-acid tracers as a benchmarking tool

To assess and improve the performance of wastewater monitoring against a known ground truth, the NAO has developed a unique library of DNA-based, non-toxic, and environmentally benign tracers for deposition into wastewater systems. The synthetic genomes encapsulated in these tracers encode regions designed for detection and quantitation through qPCR, amplicon sequencing, and metagenomics, allowing the amount of tracer released at a given location to be quantitatively linked to the amount present in a downstream sample. Large-scale experiments with these tracers could help build a comprehensive understanding of the performance of wastewater disease monitoring under different conditions, bringing us closer to the goal of robust & reliable pathogen detection.

Reports & publications

  1. Indoor Air Sampling for Detection of Viral Nucleic Acids

    Justen et al. (2024)
    – SSRN

  2. Comparing sampling strategies for early detection of stealth biothreats

    Bradshaw & Grimm (2024)

  3. Inferring the sensitivity of wastewater metagenomic sequencing for pathogen early detection

    Grimm et al. (2023)
    – medRxiv

  4. Virus-like DNA tracers for characterizing wastewater-based pathogen monitoring systems

    Gopal et al. (2023)
    – bioRxiv