EPSRC Hub for Quantitative Modelling in Healthcare

Lead Research Organisation: University of Exeter
Department Name: Mathematics

Abstract

Our Hub brings together a team of mathematicians, statisticians and clinicians with a range of industrial partners, patients and other stakeholders to focus on the development of new quantitative methods for applications to diagnosing and managing long-term health conditions such as diabetes and psychosis and combating antimicrobial infections such as sepsis and bronchiectasis. This approach is underpinned by the world-leading expertise in diabetes, microbial communities, medical mycology and mental health concentrated at the University of Exeter. It uses the breadth of theoretical and methodological expertise of the Hub's team to give innovative approaches to both research and translational aspects.

Although quantitative modelling is a well-established tool used in the fields of economics and finance, cutting-edge quantitative analysis has only recently become possible in health care. However, up to now it has been restricted to health economics in the context of healthcare services and systems management. Applications to develop future therapies, optimising treatments and improving community health and care are in its infancy. This is due to a number of challenges from both mathematical (methodological) as well as clinical and patients' perspectives. Our Hub approach will allow us to develop novel statistical and mathematical methodologies of relevance to our clinical and industrial partners, informed by relevant patient groups. Building this new generation of quantitative models requires that we advance our mathematical understanding of the effective network interaction and emergent patterns of health and disease. Clinical translation of mathematical and statistical advances necessitates that we further develop robust uncertainty quantification methodology for novel therapy, treatment or intervention prediction and evaluation.

NHS long-term planning aspires to deliver healthcare that is more personalised and patient centred, more focused on prevention, and more likely to be delivered in the community, out of hospital. Our Hub will contribute to this through developing mathematical and statistical tools needed to inform clinical decision making on a patient-by-patient basis. The basis of this approach is quantitative patient-specific mathematical models, the parameters of which are determined directly from individual patient's data.

As an example of this, our recent research in the field of mental health has revealed that movement signatures could be used to distinguish between healthy subjects and patients with schizophrenia. This hypothesis was tested in a cohort of people with schizophrenia and we developed a quantitative analysis pipe line allowing for classification of individuals as healthy or patients. The features used for classification involving data-driven models of individual movement properties as well as measures of coordination with a virtual partner were proposed as a novel biomarker of social phobias. To validate this in an NHS setting, we have recently carried out a feasibility study in collaboration with the early intervention for psychosis teams in Devon Partnership Mental Health Trust. The success of this study could significantly advance the early detection of psychosis by enabling diagnosis using novel markers that are easily measured and analysed and improve accuracy of diagnosis.

Indeed, personalised quantitative models hold the promise for transforming prognosis, diagnosis and treatment of a wide range of clinical conditions. For example, in diabetes where a range of treatment options exist, identifying the optimal medication, and the pattern of its delivery, based upon the profile of the individual will enable us to maximise efficacy, whilst minimising unwanted side effects.

Planned Impact

The Hub will serve as a focal point that brings together a wide-range of end users with the most appropriate for their needs academic expertise available at the University of Exeter in order to deliver our impact strategy. We will engage directly with clinical partners, the wider research community and industry, as well as outreach to patient and the wider public, and via capacity building on the interface of mathematics and healthcare. The activities in WP3 will in particular provide mechanisms for user engagement driven by user needs and priorities that align with the Hub Research Themes.

* NHS: The Hub will create impact for the NHS in terms improved delivery of services that is of interest to health sector managers and policy makers. Quantitative Modelling (QM) in Healthcare involving dynamic models of complex disease along with uncertainty quantification for personalised prognosis and diagnosis could result in significant cost savings to the NHS. The novelty of the Hub is that it endeavours to open new avenues of application of QM in healthcare for much wider range of problems and applications.

* Clinicians: The Hub will to create impact for clinicians by collaborative development of tools that use of quantitative models for personalising diagnosis and predicting treatment responses or outcomes. Multiple health conditions and healthcare providers could benefit from this approach, via applying cutting edge research in a clinical setting that may lead to earlier, more cost effective and more reliable diagnosis. The Hub will promote this through its network of basic researchers and clinical partners through via WP3. For example, researchers at Exeter and clinicians from RD&E are interested in quantifying the link between personal interventions and ongoing metabolic (e.g. microbiomes and endocrine function) health based on monitoring key bio indicators such as lipids or cholesterol.

* Patients: The Hub aims to develop quantitative tools for health management at personalised level. We will pursue active engagement with patients' groups such as the Lived Experience Group at the Mood Disorder Centre. Specifically we will work with patient representatives to develop appropriate public involvement and engagement activities by providing a fresh perspective and encourage researchers to think about the societal problems their research is addressing; commenting on language used in public facing communications; helping prepare for public presentations or outreach events.

* Industry: There is a real potential to incorporate quantitative models including uncertainty quantification into both new and existing healthcare technologies, i.e. into technology and tools for areas such as mental health management. There is further potential for the quantitative models and associated uncertainty quantification tools developed within the Hub to deliver precision medicine technologies for metabolic health and novel antimicrobial therapies.

* Public outreach: Healthcare is an issue that affects all of us at some time as patients or carers and unsurprisingly there is a high level of public interest and newsworthiness of new developments that may revolutionise aspects of healthcare. What is less familiar is the role of mathematics in this, and the Hub will provide a forum to educate on aspects of this.

* Impact via research team training: The Hub will support the training of two postdoctoral researchers and at least 4 PhD students through joint University and industry support. This will include both generic and specific training at the core of mathematics for healthcare. In the longer term this approach will increase the number of highly trained researchers working on the interface between mathematics and healthcare, and so build capacity to ensure that an increasingly data-rich area of healthcare science will pull through to impacts.

Publications

10 25 50
 
Description Key findings related to the Hub's Research themes:
Theme 1: Uncertainty quantification (UQ) for computational modelling in biomedicine and healthcare.
We have developed a framework that allows for quantification of uncertainty in modelling patients trajectories (disease progression) in chronic disease such as Duchenne muscular dystrophy (DMD) and lung diseases (COPD, bronchiectasis). The results from this research are being explored in terms of informing therapy and clinical trials design.

Theme 2: Reversibility and Resilience(RR): A Mathematical Approach to Evolving Microbial Communities.
A framework for modelling combination therapy for infectious disease is being developed including phage therapy. This has implications for precision medicine in this space.
Exploitation Route Clinical decision making, clinical trials secondary analysis and design.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Determining the membrane circadian clock across evolution
Amount £545,754 (GBP)
Funding ID BB/W000865/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2021 
End 08/2024
 
Description NetClamp: conducting neural network rhythms with mathematics
Amount £201,337 (GBP)
Funding ID EP/V048716/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 06/2021 
End 06/2023
 
Description The amygdala, a key upstream regulator of the hypothalamic GnRH pulse generator
Amount £391,816 (GBP)
Funding ID BB/W005883/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 02/2022 
End 01/2025
 
Description Uncertainty Quantification at the Exascale (EXA-UQ)
Amount £1,006,031 (GBP)
Funding ID EP/W007886/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2021 
End 08/2024
 
Description Understanding molecular accumulation in single cells via microfluidics and omics
Amount £512,141 (GBP)
Funding ID BB/V008021/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 05/2021 
End 04/2024
 
Title The antibiotic dosage of fastest resistance evolution: gene amplifications underpinning the inverted-U (dataset) 
Description This is the dataset used for the Reding et al. (2021) article "The Antibiotic Dosage of Fastest Resistance Evolution: gene amplifications underpinning the inverted-U" published in Molecular Biology and Evolution. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact To early to tell 
URL https://ore.exeter.ac.uk/repository/handle/10871/125077
 
Title hormoneBayes 
Description hormoneBayes is a novel open-access Bayesian framework that can be easily applied to reliably analyze serial LH measurements to assess LH pulsatility. The framework utilizes parsimonious models to simulate hypothalamic signals that drive LH dynamics, together with state-of-the-art (sequential) Monte-Carlo methods to infer key parameters and latent hypothalamic dynamics. We show that this method provides estimates for key pulse parameters including inter-pulse interval, secretion and clearance rates and identifies LH pulses in line with the current gold-standard deconvolution method. We show that these parameters can distinguish LH pulsatility in different clinical contexts including in reproductive health and disease in men and women (e.g., healthy men, healthy women before and after menopause, women with HA or PCOS). A further advantage of hormoneBayes is that our mathematical approach provides a quantified estimation of uncertainty. Our framework will complement methods enabling real-time in-vivo hormone monitoring and therefore has the potential to assist translation of personalized, data-driven, clinical care of patients presenting with conditions of reproductive hormone dysfunction. 
Type Of Material Computer model/algorithm 
Year Produced 2022 
Provided To Others? Yes  
Impact Too early to say. 
URL https://git.exeter.ac.uk/mv286/hormonebayes
 
Description Anxiety, PTSD, psychosis modelling 
Organisation University of Exeter
Department Mood Disorders Centre Exeter
Country United Kingdom 
Sector Academic/University 
PI Contribution Modelling and analysis of EEG, movement and physiological data
Collaborator Contribution Providing data and domain expert knowledge
Impact Joint MSc and PhD students supervision, collaboration on EPSRC Impact Acceleration award, involving clinical psychology, data science and modelling
Start Year 2019
 
Description Certus Technolgy 
Organisation Certus Technology
Country United Kingdom 
Sector Private 
PI Contribution Modelling patients disease trajectory
Collaborator Contribution Data
Impact Modelling framework and draft manuscript
Start Year 2021
 
Description Medicines Discovery Catapult (MDC) 
Organisation Medicines Discovery Catapult
Country United Kingdom 
Sector Private 
PI Contribution Industrial Seed Corn Funding to develop a 'Translational Roadmap' with the Medicines Discovery Catapult The aim of this award is to accelerate the translation of promising medicines discovery research underway at the University of Exeter. This call is being proposed for working jointly with the Medicines Discovery Catapult (MDC), an orgranisation dedicated to accelerating drug discovery in the UK, as part of a new strategic partnership between the two institutions.
Collaborator Contribution The MDC's VR&D team has substantial drug discovery expertise, and its members have held external innovation roles in large pharmaceutical organisations. In brief, a translational roadmap could broadly consist of (but is not limited to) the following elements: - Application of industrial rigour to review all data associated with the project - Planning of the most efficient/effective line of site to clinic, plausibly with costs & routes to delivery - Understanding of regulatory considerations - Understanding of the market and therapeutics currently in development - Understanding the suitability of the therapeutic to the patient population in question
Impact Joint projects
Start Year 2020
 
Description Microbiomes in respiratory disease 
Organisation Nanyang Technological University
Country Singapore 
Sector Academic/University 
PI Contribution Developing integrative macrobiotics framework for respiratory disease stratification and AMR
Collaborator Contribution Domain expert knowledge and data
Impact A number of publications in high profile and clinical journals, involving modelling, data analytics, bioinformatics and clinical expertise
Start Year 2020
 
Title Dynamic Clamp Controller 
Description Dynamic Clamp Controller is a lightweight GUI for uploading parameters to the excellent Arduino and Teensy-based dynamic clamp (https://www.eneuro.org/content/4/5/ENEURO.0250-17.2017). 
Type Of Technology Software 
Year Produced 2019 
Open Source License? Yes  
Impact Too early to say 
URL https://github.com/kyle-wedgwood/DynamicClampController
 
Title hormoneBayes 
Description hormoneBayes is a novel open-access Bayesian framework that can be easily applied to reliably analyze serial LH measurements to assess LH pulsatility. The framework utilizes parsimonious models to simulate hypothalamic signals that drive LH dynamics, together with state-of-the-art (sequential) Monte-Carlo methods to infer key parameters and latent hypothalamic dynamics. We show that this method provides estimates for key pulse parameters including inter-pulse interval, secretion and clearance rates and identifies LH pulses in line with the current gold-standard deconvolution method. We show that these parameters can distinguish LH pulsatility in different clinical contexts including in reproductive health and disease in men and women (e.g., healthy men, healthy women before and after menopause, women with HA or PCOS). A further advantage of hormoneBayes is that our mathematical approach provides a quantified estimation of uncertainty. Our framework will complement methods enabling real-time in-vivo hormone monitoring and therefore has the potential to assist translation of personalized, data-driven, clinical care of patients presenting with conditions of reproductive hormone dysfunction. 
Type Of Technology Software 
Year Produced 2022 
Open Source License? Yes  
Impact Too early to say. 
URL https://git.exeter.ac.uk/mv286/hormonebayes
 
Description Exeter Summit - Building Better Together, interdisciplinary Q&A panel session on Planetary Health and the recovery from COVID-19 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Exeter Summit - Building Better Together, interdisciplinary Q&A panel session on Planetary Health and the recovery from COVID-19
Year(s) Of Engagement Activity 2021
 
Description From Enigma to the Programming of Life: Alan Turing's achievements explored in a discussion between Dr Kyle Wedgwood and Sir Dermot Turing. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact This public lecture, which is hosted by the EPSRC Hub for Quantitative Modelling in Healthcare, is intended to provide a platform for people to separate truth from fiction in the story of Alan Turing's scientific accomplishments.
Guest speaker, Sir Dermot Turing will be joined by Dr Kyle Wedgwood (lecturer in the Living Systems Institute) to discuss and explore the scientific achievements of Alan Turing across his career. Starting from the efforts to "break" the Enigma machine, Dermot will decipher the real story of Alan Turing's work.
Over the course of the evening, Dermot and Kyle will reflect on the impact of Alan Turing's early machines on the development of modern computers, and later, on his contribution to answering fundamental questions about life and the natural world.
Year(s) Of Engagement Activity 2022
URL https://www.eventbrite.co.uk/e/public-lecture-alan-turing-coding-for-life-tickets-254524237847
 
Description Fungicast podcast. Neil Gow joins Sarah Campbell to explore the potency, power and potential of fungi with Merlin Sheldrake 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Fungicast podcast. Neil Gow joins Sarah Campbell to explore the potency, power and potential of fungi with Merlin Sheldrake
Year(s) Of Engagement Activity 2021
URL https://soundcloud.com/user-621263983/fungicast-episode-1-with-merlin-sheldrake-and-neil-gow
 
Description Futures 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact MakeTank, Paris Street, Exeter by Kyle Wedgwood
Year(s) Of Engagement Activity 2021
URL https://www.maketank.org.uk
 
Description How was it done? Breaking the Enigma cipher - maths, not magic with Dermot Turing. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact The Enigma machine cipher was famously broken at Bletchley Park, but for many years GCHQ did not want anyone to know how it was actually done. Beginning with the Enigma machine itself, and its illusory security features, this presentation travels across the different attacks on Enigma from the earliest pre-war attempts to the later sophisticated machine decryption methods. These attacks drew on group theory and the post-Hilbert ideas of incomplete logical systems as well as more traditional cryptanalytical approaches based on language structure. Once the theory was established, creating a fast, workable system for finding Enigma keys required an engineering solution, using binary logic to eliminate wrong settings - a radically new approach leading to the ascendancy of digital computing. Dermot Turing is the acclaimed author of Prof, a biography of his famous uncle, The Story of Computing, and most recently X, Y and Z - the real story of how Enigma was broken.
Year(s) Of Engagement Activity 2022
URL https://www.exeter.ac.uk/news/events/details/index.php?event=11977
 
Description Killer Fungus talk, British Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Killer Fungus talk, British Science Festival by Neil Gow
Year(s) Of Engagement Activity 2021
URL https://britishsciencefestival.seetickets.com/content/ticket-options
 
Description Mathematical Modelling meets Medical Mycology 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Mathematical Modelling meets Medical Mycology engagement event organised by one of the Hub's fellows - Nicolás Verschueren van Rees.
The event took place on 11 November 2022 in Reed Hall, University of Exeter, UK
Year(s) Of Engagement Activity 2022
URL https://www.exeter.ac.uk/news/events/details/index.php?event=12433
 
Description Mathematics in Life Sciences workshop: New developments in pattern formation in biological systems, University of Exeter, 14-15th June 2022. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact The meeting will focus on "New developments in pattern formation in biological systems" and will take place on the 14-15th June 2022 from 13:30 (14th June) to 14:00pm (15th June) in the Newman Red Lecture Theatre in the Peter Chalk Centre, at the University of Exeter (Streatham Campus).
Year(s) Of Engagement Activity 2022
URL https://mils.ghost.io/programme-mils-meeting-on-pattern-formation/
 
Description MiLS meeting on "Linking Mathematics, Experiments and Data" 8th-9th March 2023, University of Exeter 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact The meeting will focus on "Linking mathematics, experiments and data" and will take place on the 8-9th March 2023 from 11:30 (8th March) to 13:30pm (9th March) in the Harrison Building at the University of Exeter (Streatham Campus).
Year(s) Of Engagement Activity 2023
URL https://mils.ghost.io/hybrid/
 
Description School visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Title: "Mathematical models of hormonal rhythms" seminar by Dr Margaritis Voliotis
Date: 04/03/2022
Venue: South Gloucester and Strout College (SGS), STEM Seminar series
Year(s) Of Engagement Activity 2022
 
Description Screening of 'Our Body is a Planet' followed by discussion between artist and Neil Gow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Screening of 'Our Body is a Planet' followed by discussion between artist and Neil Gow in Exeter Phoenix
Year(s) Of Engagement Activity 2022
URL https://exeterphoenix.org.uk/events/our-body-is-a-plant/
 
Description THE FUTURE OF AI 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact THE FUTURE OF AI
AI is at a crucial point: in this event discover its radiant possibilities as well as the possible changes to all our lives. A world leading panel of experts from business, finance, media and academia discuss the eye-opening scenarios of our future.
There is a particular focus on how AI is used to make models for our decisions, regulate our systems, and reduce the impact of uncertainty to solve real-world problems
Which areas of our lives will have the most rapid changes? What does this tell us about what it means to be human?
Year(s) Of Engagement Activity 2022
URL https://exeterphoenix.org.uk/events/the-future-of-ai/
 
Description Talk at Chumleigh college on research in mathematics, 28th February 2023. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk at Chumleigh college on research in mathematics, 28th February 2023.
Year(s) Of Engagement Activity 2023