Advancements in genome sequencing technologies are rapidly reshaping how the U.S. detects, monitors, and responds to infectious disease threats. The National Academies of Sciences, Engineering, and Medicine’s July 2024 workshop, “Accelerating the Use of Pathogen Genomics and Metagenomics in Public Health,” convened leading experts across sectors to assess the current landscape, identify roadblocks, and chart a path forward. The resulting workshop report captures a crucial moment in the evolution of genomic epidemiology in U.S. public health.
Unlocking the Potential of Pathogen Genomics
Next-generation sequencing (NGS) and metagenomics are enabling unprecedented insights into pathogen detection, outbreak source tracing, antimicrobial resistance (AMR), and vaccine development. Decreasing sequencing costs—from $10 million per megabase in 2001 to less than one cent today—have made these tools more accessible and scalable.
Whole genome sequencing (WGS) has already replaced traditional subtyping techniques for foodborne pathogens and tuberculosis, and is rapidly expanding into outbreak detection, drug resistance profiling (e.g., Mycobacterium tuberculosis), and high-consequence pathogens like HIV and malaria. During the COVID-19 pandemic, genomics was instrumental in variant detection and intervention planning.
National Programs Driving Innovation
The CDC’s Advanced Molecular Detection (AMD) program and its $40 million annual budget have catalyzed national capacity-building since 2013. Key achievements include:
- Expansion of WGS capacity to every U.S. state public health lab.
- Launch of the SPHERES consortium (1,800+ scientists, 200+ institutions) for collaborative SARS-CoV-2 sequencing.
- Creation of the Pathogen Genomics Centers of Excellence (PGCoEs), linking public health departments with academic partners to advance applied genomics R&D and workforce development.
However, speakers emphasized that surveillance readiness does not automatically equate to outbreak readiness—bioinformatics capacity, data integration tools, and rapid pivoting to new pathogens remain critical gaps.
State-Level Successes and Challenges
State case studies—particularly from the Minnesota Department of Health—demonstrated the power of genomics in real-world investigations:
- Listeria outbreak tracing: Genomic analysis linked a fetal demise case to imported Ecuadorian cheese, leading to regulatory action and consumer warnings.
- COVID-19 transmission mapping: Sequencing traced outbreaks across long-term care and correctional facilities to household transmission, aiding targeted interventions.
- Streptococcus surveillance: Multi-facility outbreaks were traced to a single healthcare provider using genomics, leading to rapid infection control.
Despite these advances, uneven capacity across states and variable data-sharing laws create inconsistencies. Efforts such as the Public Health Bioinformatics Fellowship and PGCoEs aim to narrow this gap through shared resources and training.
Key Challenges Identified
1. Infrastructure and Interoperability
Bioinformatics platforms, cloud storage, and analytic pipelines remain fragmented across states and agencies. CDC’s modular AMD Platform aims to standardize access and processing capabilities.
2. Ethical and Legal Barriers
Data privacy and ownership issues, especially surrounding human genome sequences, complicate public health data sharing. Notifiable disease data collected without consent may restrict external use, even when genomic data alone may not reveal identities.
3. Diagnostic Integration and Regulation
Sequencing-based diagnostics face regulatory hurdles due to pipeline variability and lack of standardization. WGS diagnostics have been FDA-approved for HIV, but broader adoption remains limited.
4. Cost Beyond Sequencing
Sequencing itself is becoming cheaper, but total costs—including sample processing, metadata collection, and expert analysis—remain high and require sustained investment.
The Road Ahead: Toward Proactive Surveillance
Participants agreed that pathogen genomics must evolve from a reactive tool into a proactive foundation for public health decision-making. Key recommendations included:
- Investing in workforce development to close bioinformatics skill gaps.
- Developing integrated data systems for real-time epidemiological and genomic analysis.
- Creating federal–state–academic networks for joint innovation, training, and surge response.
- Expanding metagenomics use cases, especially for difficult-to-culture pathogens and early warning in environmental samples like wastewater.
The PGCoE model, collaborative consortiums like SPHERES, and infrastructure investments such as the AMD Platform represent promising pathways to advance pathogen-agnostic surveillance and response.
Pathogen genomics is not a future tool—it is a present necessity. As new threats emerge and old ones evolve, the U.S. public health system must move beyond fragmented, pathogen-specific efforts toward integrated, scalable, and ethically governed genomics capabilities. Cross-sector collaboration, sustained funding, and data infrastructure modernization are essential to realize the full potential of genomics in protecting public health.
Accelerating the Use of Pathogen Genomics and Metagenomics in Public Health: Proceedings of a Workshop. National Academies of Sciences, Engineering, and Medicine. June 2025