iSEP-SEQ gap fund
Research type
Research Study
Full title
iSEP-SEQ: Integrated workflow for SEPsis and infectious diseases diagnosis with a microbial cell-free DNA SEQuencing approach
IRAS ID
342019
Contact name
Maiwenn Kersaudy-Kerhoas
Contact email
Sponsor organisation
Heriot-Watt University
Duration of Study in the UK
1 years, 6 months, 1 days
Research summary
Sepsis kills someone every few seconds globally, and results in 48,000 deaths per year in the UK, inflicting an estimated economic toll of £10 billion. The current standard for pathogen identification is blood culture which is too slow to guide the management of sepsis patients which must be done in hours. Protein-based biomarker approaches offer faster alternatives but cannot directly identify causative pathogens. Molecular approaches (e.g. PCR) offer a limited range when multiple aetiological agents must be considered. In contrast, the analysis of microbial cell-free DNA (cfDNA), released from lysed pathogens in the infected human blood circulation, is an unbiased and sensitive way to detect infectious pathogens, including those that cannot be cultured such as viruses, fungi and protozoa. Being able to rapidly identify any infecting pathogen is a long-standing challenge in global health. Doing so from a non-cultured blood sample in a matter of hours would present a game-changing approach to the determination of sepsis and other disease causes, reducing the need for broad-spectrum antibiotics with their adverse side effects and risk of resistance.
Our team at Heriot-Watt University has developed a cfDNA assay which combines a patented microfluidic system for cfDNA extraction, and real-time sequencing. Our approach, named iSEP-SEQ, will reduce the time to result to under six hours, a leap from existing Next-Generation Sequencing (NGS) solutions which take 48h or more. We have demonstrated the validity of our rapid cfDNA extraction on over 400 human samples and piloted iSEP-SEQ workflow on 10 archived samples from septic patients. Although we have initially demonstrated the potential of this technique, we have not yet demonstrated in real-time its ability to identify pathogens in under six hours from unwell patients.
Using 100 fresh blood samples from NHS Tayside septic patients, this project aims to evaluate, in collaboration with the Universities of St Andrews and Dundee, and the National Infectious Disease Institute, iSEP-SEQ's overall performance and clinical applicability in the rapid near-patient identification of pathogens from non-cultured blood samples. The National Measurement Laboratory, the UK’s designated institute for chemical and bio-measurements, will provide robust statistical analysis and oversight on the validation and method performance for future regulatory approval.
The project has received support from the Global Sepsis Alliance, the UK Sepsis Trust, Sheikh Shakhbout Medical City, The University of Edinburgh, UniverstatsMedizin Mainz (Germany), Aichi Medical University (Japan), National Institute of Infectious Diseases (NIID, Japan), Public Health Scotland, and Oxford Nanopore, who will bring in the patient voice, additional clinical perspectives and technical support to the project.
The iSEP-SEQ approach will bring unbiased large-range pathogen identification to the clinic and aid timely medical decisions by identifying any class of microorganism present in the sample, including bacteria, fungi, parasites and viruses.
iSEP-SEQ aligns strongly with the UK Health Security Agency's 5-year Pathogen Genomics Strategy published in January 2024, specifically with Strategic Aim 1 and Strategic Aim 6: The emphasis on utilizing genomic data for informed decision-making in clinical and public health, as well as driving innovation in pathogen genomics, is crucial for effectively addressing and responding to public health threats. The support from Public Health Scotland further underscores the significance of iSEP-SEQ in contributing to these strategic aims.
iSEP-SEQ has the potential to transform sepsis, febrile and acute disease diagnosis, reduce patient morbidity and mortality, and combat antimicrobial resistance.
REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
25/EE/0010
Date of REC Opinion
7 Apr 2025
REC opinion
Further Information Favourable Opinion