Corporate report

UKHSA Advisory Board: Pathogen Genomics Programme

Updated 11 March 2025

Date: March 2025

Sponsor: Susan Hopkins

1. 1. Purpose of the paper

The purpose of the paper is to provide an update on the progress of the Pathogen Genomics Programme that was approved by the UKHSA Investment Board in June 2024.

2. 2. Recommendations

The Advisory Board is asked to note the Genomics Programme progress update.

3. 3. Programme progress

3.1 Background

Following approval of the Genomics Strategy in January 2024, the Genomics Programme business case was approved by the UKHSA Investment Board in June 2024. The programme aims to deliver integrated end to end pathogen genomics in three priority areas (emerging infections, vaccines and antimicrobial resistance) as well as systematic organisational transformation in genomics delivery, infrastructure and workforce. The programme includes initiatives using both whole genome sequencing (WGS), and newer metagenomics. UKHSA is providing UK and global leadership for pathogen genomics for diagnostic and surveillance purposes with the work underpinned by health economics, cost effectiveness and value for money. The overall programme was initially phased over 2 years (April 2024 to March 2026) as £38 million but due to other priorities the same funding has been reprofiled over 3 years within the same financial envelope.

3.2 Progress

Since programme approval, the priority projects we will support under our 3 priority areas have been defined and agreed, as below. Progress has been made with each of these projects.

3.3 Vaccine preventable diseases

Establishment of the Hepatitis C virus (HCV) genomics surveillance programme. The process for the regular collection of residual plasma samples from NHS labs has now been defined, and sequencing is currently underway, with an additional 1,500 samples sequenced at UKHSA laboratories in financial year (FY) 2024 to 2025 The genomic data will be linked to epidemiological and clinical databases at UKHSA to optimise the NHS treatment strategies and public health interventions to prevent onward transmission with an analysis of cost-effectiveness.

Evaluation of next-generation sequencing methodology for measles characterisation, development of the appropriate bioinformatics pipeline and WGS of 600 samples. Control and outbreak samples have been shipped to Manchester UKHSA laboratory and method optimisation and sequencing have commenced. This will enable better determination of imported and associated linked cases to deliver elimination goals.

Development of the mycobacterial tuberculosis (TB) pipeline. We have confirmed UKHSA as leading in the development of this pipeline for the 4 nations and have agreed via a memorandum of understanding how this pipeline group will be governed. We have also outlined options for the current (TB Compass) contingency pipeline and are progressing a contingency solution with the supplier Ellison Institute of Technology. Development of a new WGS pipeline for TB to enable mycobacterial speciation, drug resistance prediction for TB complex and relatedness is underway. This development project has thus far refactored the components included within the pre-existing lodestone project, rebuilding them into containerised functional components wrapped in an end-to-end Nextflow workflow manager. The current development focus is on initial testing of components, bug-fixing and evaluation of additional tools, as a prequel to large scale validation of data sets derived from within UKHSA, publicly available data sets from nucleotide archives and synthetic data (simulated to test explicit components). TB whole genome sequencing and public health analysis delivers immediate patient benefits with faster time to effective treatment, optimal detection of TB clusters and associated control measures.

3.4 Anti-microbial resistance (AMR)

Whole Genome Sequencing of the Clostridioides difficile (C. difficile) ribotype library, Laboratory Information Management System (LIMS) configuration and training at the Leeds laboratory, and bioinformatics pipeline validation, implementation and deployment at UKHSA. Sentinel sites have been invited ahead of the launch date on 1 April 2025. This project enables the detection of a novel or emerging strain with antimicrobial resistance or with virulence or associated with significant morbidity and mortality. Sentinel sites have been selected to optimise the detection in the NHS from most connected hospitals.

Assess and apply long-read sequencing methodology for Carbapenamase-producing Enterobacterales (CPE). CPE are bacteria which are multi-drug resistant and with the highest mortality. Understanding how these spread (both for the mobile genetic elements and the strains of bacteria) in the NHS is essential to maintain control. The sequencing of the background dataset of 200 isolates is currently underway at the Colindale laboratory.

3.5 Emerging infections and biosecurity

Providing global and national genomics horizon-scanning function for respiratory, vector borne and contact diseases

Using genomic data to assess the risk from emerging and zoonotic infections and provide reactive analysis for major national outbreaks. This has been used to manage the H5N1 response including the ability to tailor health protection activities to level of risk with cost savings for health protection teams during the avian influenza season in the UK.

mSCAPE (metagenomics Surveillance Collaboration and Analysis Programme) and the development of metagenomic surveillance

mSCAPE is an internationally leading programme to pilot the use of clinical metagenomic data for public health surveillance and biosecurity. It has been publicly launched on the 30 January and is now live, receiving data from the NHS sites to a new central data platform. It works in partnership with three universities and the NHS Genomics Network of Excellence rollout of diagnostic metagenomics.

Development of clinical metagenomics services

The Rare and Imported Pathogens Lab (RIPL) are developing a metagenomics service for undiagnosed imported fevers. The pilot service went live in January 2025 with first samples received in February 2025. Respiratory metagenomics services are underway in two UKHSA regional labs, as part of the NHSE Genomics Network of Excellence rollout. Validation of the service is estimated by March 2025. This data will also contribute to mSCAPE.

Environmental surveillance

Feasibility study using aircraft wastewater collected from international flights. We have an agreement for the collection of 36 samples for PCR analysis and 60 bio-banked samples for metagenomic analysis which are currently being received at UKHSA Porton. The metagenomic analysis is being undertaken in Porton (SISPA method) and Colindale (Capture method) from January 2025 and will provide evidence on the feasibility and potential public health value of establishing a UKHSA sample collection from aeroplane wastewater to guide genomics surveillance programmes in this area.

As well as our priority projects above, there are 7 additional workstreams within the programme.

For example, Data Integration aims to put in place effective data structures and pathways for integration of genomic, epidemiological, and other datasets. To date, a proof of concept ​has been agreed and 5 work packages defined. We are currently defining the components of these work packages and have recruited contingent labour to deliver the design element by March 2025.  We have also been working to improve the resilience of the infrastructure used to process WGS data. Almost all WGS pipelines have been migrated from legacy high-performance compute to newer compute which is effectively replicated between two UKHSA sites offering greater resilience for the WGS service. This transfer of pipelines to new infrastructure has required modernisation of the software stack used to process WGS data and all pipelines and now following the model of containerised modular code linked with Nextflow to manage the workflow. The Salmonella pipeline is due to be migrated in March 25 and the new TB pipeline is also being developed to fit with the new deployment model. This transformation of the existing WGS pipeline deployment model was designed to enable deployment of WGS pipelines on cloud compute and work on an initial cloud deployment has been started using a high-performance compute cluster built on AWS.

During the programme, we have reprioritised work as required. Further details are outlined in section 4. One area we have prioritised is the TB workstream due to the criticality of the 72-hour turnaround time for patient sequencing analysis. Here, we have redeployed bioinformatician resource to progress with pipeline development.

4. 4. Key challenges to delivery

4.1 Leadership changes

There have been several challenges to programme delivery since business case approval. Notably, there have been 3 changes to Science senior leadership in 2024, which has impacted the Workstream Lead representation for Science. This has led to the delay of planning and approvals for work in this area.

4.2 Recruitment

A large portion of the allocated funding for the programme in 2024 to 2025 was forecasted against new recruitment to support delivery. However, the UKHSA wide recruitment freeze prevented the programme from recruiting into 26 vacant posts. Following this, the UKHSA wide request to reduce financial pressure across the organisation led to a £1.5 million cut of the £12 million allocated spend for the genomics programme for 2024 to 2025. This has been reprogrammed to 2026 to 2027.

5. 5. Programme successes to date

5.1 Data Sharing

The Data Sharing Standard Operating Procedure (SOP) was published internally in January 2025. This defines risk assessment criteria by which pathogens can be assessed as ‘green’, ‘amber’ or ‘red’ in terms of being able to share specific pathogen sequence data. A green rated pathogen indicates that the genomic data for that pathogen should be made publicly available. The SOP also includes the defined green list of pathogens that the genomics team have risk assessed and agreed. A slimmed down version of this document was published externally in January 2025. New data sharing for the green list pathogens can now be implemented across the coming financial year.

5.2 mSCAPE

The surveillance pilot went live in December 2024 with all ethical, security and operational requirements in place to accept clinical data for severe respiratory infections and undiagnosed imported fevers. A number of sites have been onboarded onto the platform from across the Genomics Network of Excellence NHS sites and are submitting clinical sample data as well as data from controls. Set up for going live involved contracting academic partners, seeking ethical approvals, data platform design, information governance work incorporating novel privacy issues relating to metagenomic data, implementing genomic detection and analysis pipelines, including analysis for quality control on positive and negative controls.

5.3 RIPL

The RNA (ribonucleic acid) pipeline for the clinical metagenomics project was successfully completed in October 2024. Data has been generated for the validation of the assay from several RNA viruses of importance to RIPL and this data was used to generate an In Vitro Diagnostics Directive (IVDD) file for the assay to enable its use for clinical samples. Approval was granted by the Research Ethics and Governance Group (REGG) in January 2025 to allow a clinical pilot study to take place to assess the use of the RNA pipeline assay on selected clinical samples received by RIPL over the next 6 months. Data generated from this study will be used to provide evidence for the IVDD file.

5.4 Developing ethical framework

We have worked to present our data-sharing work publicly, work with ethicists in considering how we can deliver our work safely and ethically through public engagement. We have presented this to the ethics and equality committee (Annex A).

6. 6. Programme forward look

Our key milestones for the year ahead include:

• delivery of the mSCAPE pilot, including evaluation of mSCAPE analysis components against routine surveillance data for winter 2025 to 2026

• genomics training underway for the development of genomics literacy across UKHSA

• the TB Compass pipeline contingency to be delivered and the Compass pipeline replaced

• data integration work packages to be delivered and transitioning to business as usual

7. 7. Demonstrating value for money

A breakeven analysis for HCV was captured in the original programme business case. The programme has worked closely with the Health Economists to continue quantifying benefits within genomics. A quantified analysis on the Technology workstream has now been included in the updated programme business case, for Investment Board approval in March 2025. As well as this, we have put in place an academic agreement with Imperial to work on developing a more robust case study for HCV and have built in a dedicated Health Economist to business planning for 2025 to 2026 to focus on the evaluation of mSCAPE.

8. 8. Programme impacts

The programme will deliver benefits in each area, and benefits measurement is being supported on an ongoing basis by the UKHSA Health Economist team. To note some of the impacts our priority projects will have:

• the tuberculosis (TB) project that focuses on rapid and automated WGS will contribute to the control of TB and treatment of patients through rapid reliable AMR diagnosis and cluster detection – this will also reduce resource burdens on UKHSA TB teams

• the programme’s measles project will help us to understand epidemiology in the UK and inform vaccine strategy, as well as contribute to global control efforts as a World Health Organization collaborating centre amidst a deteriorating global measles situation

• our Horizon Scanning project will ensure that DHSC advisory committee risk assessments are now fully informed by global genomic data – in 2024, avian influenza horizon scanning was used to reduce use of antivirals during the winter season and reduce Health Protection Teams workload (it was also used to step-down incident response to a recent human case​)

• metagenomic development is aiming to improve time to detect

• the implications on health inequalities and ethics were discussed at the UKHSA Ethics, Equalities and Communities Committee in January 2025

9. 9. Key external partners

External stakeholders and partnerships are essential to achieve successful programme delivery. Notably, the programme has developed key relationships with those listed below.

9.1 NHSE genomics networks of excellence

These networks, funded by NHSE, aim to foster excellence in genomics by creating pathogen genomics hubs that link closely with UKHSA. These hubs are intended to serve as centres for innovation, expertise, and resource pooling, facilitating the rapid identification and characterisation of pathogens using metagenomics. Collaboration between UKHSA and NHSE is ensuring that genomic insights are seamlessly integrated into clinical care, enhancing patient outcomes and public health responses.

9.2 Four Nations subgroup on genomics

This subgroup fosters collaboration across the UK’s four nations on genomic surveillance and policy. It ensures that efforts in pathogen genomics are harmonised, and best practices are shared, enhancing the collective genomic capability across the UK for detecting and responding to infectious disease threats.

9.3 Industry

Companies like Oxford Nanopore Technologies (ONT), Illumina, and cloud compute providers such as Oracle and AWS, are integral to the advancement of pathogen genomics in UKHSA. These partners provide sequencing technologies (both short-read and long-read sequencing) and computational infrastructure necessary for genomic data analysis. Their ongoing innovation and support are essential to UKHSA for the scalability, efficiency, and accessibility of genomic surveillance operations. We have developed relationships through the TB contingency pipeline with Ellison Institute of Technology and through mSCAPE with ONT.

9.4 Academia

As well as our work with health protection research units, we also engage with the Wellcome Sanger Institute, UK Research and Innovation, Horizon Europe on research priorities within genomics. We are continuing to develop relationships with European Bioinformatics Institute. We work closely and directly with academia through our specific collaborations with a wide range of UK universities and the UK Pandemic Sciences Network.

Meera Chand, Deputy Director TARZET                          

Richard Myers, Deputy Director Bioinformatics

Derren Ready, Deputy Director Public Health Microbiology