Advancements in genomic technologies are revolutionizing public health surveillance in the United States. The recent workshop organized by the National Academies of Sciences, Engineering, and Medicine in July 2024, titled “Accelerating the Use of Pathogen Genomics and Metagenomics in Public Health,” brought together key stakeholders to evaluate the current landscape of genomic epidemiology, pinpoint challenges, and formulate a roadmap for future advancements. This report highlights the transformative role of genomics in detecting, monitoring, and responding to infectious diseases, illustrating both successes and ongoing challenges as the field continues to evolve.
The Transformative Power of Pathogen Genomics
Next-generation sequencing (NGS) and metagenomics technologies are providing unparalleled capabilities in pathogen detection, source tracing of outbreaks, antimicrobial resistance (AMR) assessment, and vaccine development. The dramatic decrease in sequencing costs—from around $10 million per megabase in 2001 to less than one cent today—has made these powerful tools more accessible than ever.
Whole genome sequencing (WGS) is now the standard for identifying foodborne pathogens and tuberculosis, and its applications are expanding. During the COVID-19 pandemic, genomics played a critical role in identifying and responding to viral variants, thereby enhancing public health strategies and intervention plans.
National Initiatives Driving Genomic Innovation
The CDC’s Advanced Molecular Detection (AMD) program has been a cornerstone in building genomic capabilities across the nation since its inception in 2013, supported by an annual budget of $40 million. Key milestones achieved by the AMD program include:
- Statewide WGS Capacity: The program has expanded WGS capabilities to public health labs in every U.S. state.
- SPHERES Consortium: This initiative comprises over 1,800 scientists and institutions dedicated to collaborative SARS-CoV-2 sequencing efforts.
- Pathogen Genomics Centers of Excellence (PGCoEs): These centers aim to connect public health departments with academia to foster applied genomics research and workforce development.
Nevertheless, the workshop revealed critical disparities between surveillance and outbreak readiness. While there is improved genomic capacity, gaps remain in bioinformatics, data integration, and the ability to swiftly adapt to new pathogens.
State-Level Applications and Challenges
Several real-world case studies highlighted the effective application of genomics in public health investigations:
- Listeria Outbreak Tracing: Through genomic analysis, a fatal case linked to imported Ecuadorian cheese prompted regulatory actions and consumer warnings.
- COVID-19 Transmission Mapping: Sequencing data demonstrated how outbreaks extended from households to long-term care and correctional facilities, enabling more effective public health responses.
- Streptococcus Surveillance: Genomic connections identified a singular healthcare provider as the source of multi-facility outbreaks, resulting in timely infection control measures.
Despite these successes, disparities among states in genomic capacity and varying state laws on data sharing create ongoing challenges. Initiatives like the Public Health Bioinformatics Fellowship and PGCoEs are vital for providing shared resources and training aimed at bridging these gaps.
Key Challenges to Overcome
The workshop identified several barriers that must be addressed to fully leverage the potential of pathogen genomics:
Infrastructure and Interoperability:
Bioinformatics platforms and analytical pipelines remain fragmented across states and public health agencies. The CDC’s AMD Platform is working toward standardizing access and capabilities.Ethical and Legal Barriers:
Issues around data privacy and ownership complicate public health initiatives. Concerns about human genome sequences may restrict data sharing, even when genomic information alone could not identify individuals.Diagnostic Integration and Regulation:
Regulatory challenges exist for sequencing-based diagnostics due to variability in pipelines and a lack of standardization. Although FDA approval has been granted for WGS in HIV diagnostics, broader adoption remains limited.- Costs Beyond Sequencing:
While sequencing costs have decreased significantly, the overall expenses, including sample processing and expert analysis, remain high. Continuous investment is essential to sustain these efforts.
Moving Toward Proactive Surveillance
Participants highlighted the need for pathogen genomics to transition from a reactive response tool to a proactive basis for public health decision-making. They advocated for:
- Workforce Development: Investing in training to mitigate skill gaps in bioinformatics.
- Integrated Data Systems: Developing systems for real-time analysis of epidemiological and genomic data.
- Federal-State-Academic Networks: Fostering collaborative networks for innovation, training, and responsive action to emerging threats.
- Expanded Metagenomics Applications: Encouraging the use of metagenomics for challenging pathogens and environmental monitoring, such as wastewater analysis.
The models established by PGCoEs, collaborative initiatives like SPHERES, and infrastructure investments represented by the AMD Program can significantly enhance pathogen-agnostic surveillance and response strategies.
Conclusion
Pathogen genomics is not just a futuristic tool; it is an essential component of contemporary public health infrastructure. As new infectious diseases arise and existing pathogens mutate, the U.S. public health system must evolve from isolated, pathogen-specific efforts to a more integrated and scalable genomic capability. Achieving this goal hinges on collaborative efforts across sectors, sustained funding, and modernizing data infrastructures. Embracing these challenges will ensure that genomics continues to protect and promote public health in an increasingly complex and interconnected world.
