Background and Problem Statement
Pathogen genomic sequencing is a foundational capability for modern public health surveillance. It enables the detection of outbreaks and emerging variants, characterization of transmission dynamics, monitoring of diagnostic and drug resistance, informing clinical decisions, and evaluation of intervention impact. During the COVID-19 pandemic, unprecedented investments expanded sequencing infrastructure across many LMICs. However, that capacity is largely confined to outbreak response, donor-supported pilots, and research projects. End-to-end workflows are often costly, technically complex, and dependent on fragile supply chains, cold-chain logistics, and specialized expertise. As a result, only a small fraction of clinically detected or environmentally sampled pathogens are ever sequenced, limiting the public health value of existing capacity.
Over the past decade, the cost of sequencing has decreased significantly; however, these advancements have not yet been fully translated into accessible diagnostic and population-level surveillance and routine programmatic use. Sequencing a single pathogen – viral, bacterial, or parasitic – can still exceed several hundred dollars per sample once all reagents, consumables, and logistical overhead are included. Emerging advances in protocol design, reagent chemistry, workflow simplification, and platform interoperability suggest that a fundamentally different cost and operational paradigm is now within reach.
This Grand Challenge initiative seeks to accelerate the development of low-cost, streamlined, and operationally simple targeted pathogen sequencing workflows designed for routine public health use in LMICs. We invite researchers and innovators to propose bold, scalable solutions that lower sequencing costs, simplify protocols, and democratize access to genomics.
The Challenge
We are seeking ideas that substantially lower the cost and complexity of pathogen sequencing for at least one priority pathogen or use case in Table 1. The primary objective is to drive the total sample-to-sequence cost to approximately US$1–10 per sample, while remaining fit for public-health use.
Rather than developing new sequencing hardware, this call prioritizes sequencing methodology and workflow that enables existing sequencing platforms (including, but not limited to, Illumina, Oxford Nanopore Technology, MGI/BGI, and other sequencers) to be used more affordably, reliably, and at scale. Proposed solutions should be adaptable across pathogens and platforms and explicitly designed for routine deployment in LMIC public-health laboratories (see Table 2).
We are especially interested in transformative approaches that rethink the sequencing workflow itself. At a minimum, a competitive workflow should be built on a shared laboratory backbone, complemented by interchangeable primer panels or assay modules that can be adapted quickly to different pathogens, programs, or surveillance objectives. Strong proposals will set out a clear roadmap showing how the workflow reduces protocol heterogeneity and lets laboratories pivot between pathogens without substantial retooling, retraining, or redesign.
Proposals should address the following objectives, calibrated to the maturity of the proposed solution.
- Cost reduction: Demonstrate a credible pathway to achieving per-sample costs (from sample to sequencing data) of approximately US$1–10, inclusive of reagents and consumables. Cost reductions should arise primarily from workflow and protocol-level innovation. While increased volume may contribute to incremental savings, this RFP prioritizes approaches that reduce per-sample costs through improved methods, streamlined workflows, and technical efficiencies independent of scale. Proposals should clearly articulate the assumptions underlying cost projections, including target coverage, sequencing depth, multiplexing, assay performance, and operational context, and demonstrate that affordability is achieved without compromising data quality or public-health utility. Approaches that rely primarily on increased multiplexing or throughput to reduce costs will not be prioritized. Guidance on minimum coverage and depth is provided in Table 1.
- Workflow simplification: Replace complex, multi-step, pathogen-specific protocols with streamlined, modular workflows suitable for routine public-health use. Priority areas include low-cost amplicon-based or other targeted sequencing assays; direct-from-sample amplification that reduces or eliminates dependence on culture and/or nucleic-acid extraction where technically and biologically appropriate; and integrated or "one-pot" reaction designs that consolidate processing steps and reduce hands-on time. Shelf-stable or lyophilized reagent formats are of interest where they simplify workflows, improve robustness, or reduce logistical complexity (e.g., cold-chain dependence), even if they do not by themselves lower reagent costs. Proposals should make their technical assumptions, constraints, and trade-offs explicit, including specimen requirements and performance implications.
- Platform compatibility and scalability: Proposed methods should be compatible with widely deployed sequencing platforms (including, but not limited to, Illumina, Oxford Nanopore, and MGI/BGI). Preference will be given to workflows that are compatible with multiple sequencing platforms at the assay-design level, or that clearly explain how they can be adapted across platforms with minimal modification.
- Reduced turnaround time: Proposals should clearly specify expected turnaround times for core laboratory processing steps (e.g., sample preparation, library construction, and sequencing) and describe how workflow design choices reduce turnaround time without compromising data quality.
- Demonstration of efficacy and performance: Proposals should include a clear plan to demonstrate efficacy for priority pathogens and/or use-cases (see Table 1). Applicants may submit preliminary proof-of-concept data where available; however, the primary expectation is that funded projects will generate and validate proof-of-concept evidence during the award period. Resulting data should demonstrate that the proposed low-cost sequencing approach maintains accuracy, reliability, and public-health utility comparable to current reference or gold-standard methods, appropriate to the intended pathogen and use case.
Achieving the above objectives will likely require expertise from multiple disciplines and a strong understanding of on-the-ground needs. We encourage partnerships across academic, public-health, and private-sector.