Deep Poisson process pathogen phylodynamics to accelerate understanding in disease transmission

Lead Research Organisation: Imperial College London
Department Name: Mathematics

Abstract

The discovery of deciphering the human genetic code has been a landmark scientific achievement, leading to the development of personalized medicine, gene therapies, or modern vaccines. Today, the genetic codes of major organisms, and viral or bacterial pathogens that compromise human health are identified (or sequenced) at low cost and at industrial scale, including for the purpose of reconstructing how infectious diseases spread in human populations, and how to stop spread.

The genetic relationships of pathogen variants provide objective data about who infected who, information that is otherwise hard to obtain. The mathematical and statistical theory that underlies the analysis of these data is called 'phylodynamics'. This theory has made possible to reconstruct and quantify how anti-microbial resistant pathogens have spread worldwide, in communities, or in hospital wards, or how novel COVID-19 variants emerge and replace each other.

This EPSRC project aims to develop a novel class of statistical phylodynamic theory, grounded in deep Poisson point processes, that are substantially more flexible and computationally faster than existing methods. Our preliminary findings indicate this approach has the potential to unlock the analysis of important questions about the age, behavioural characteristics, locations, mobility patterns or other characteristics of population groups that are the sources of pathogenic spread, and which to date are very challenging or impossible to address. We will develop the statistical theory and provide open-access and computationally scalable code for flexible and reproducible analyses. This project will benefit from close ties to the Machine Learning & Global Health network (development of deep non-parametric methods), the international PANGEA-HIV consortium (access to large-scale, rich and globally important data collected over the past 10 years), the UK Health Security Agency (aiming to use our methods in the UK) and to Oxford Nanopore (transitional industry impact).

Publications

10 25 50
 
Description 1/ This work contributed to substantiate earlier findings that the primary HIV transmission pathway into young & adolescent women is via substantially older men, typically >6 years older.
Exploitation Route 1/ The outcomes under point (1) listed above may be used to update HIV prevention programming in Southern and Eastern Africa.
Sectors Healthcare

URL https://www.unaids.org/en/resources/documents/2023/global-aids-update-2023
 
Description The findings from this award have substantiated earlier evidence that the primary transmission pathway into young & adolescent women is via substantially older men, typically >6 years older. These findings have been reported in the UNAIDS Global AIDS Update 2023, and thereby reached a broad audience specialising in global health and HIV prevention.
First Year Of Impact 2024
Sector Healthcare
Impact Types Policy & public services

 
Title Code for Poisson point process model for analysing transmission sources 
Description This technology asset comprises the code for the Poisson point process model for analysing transmission sources. 
Type Of Material Technology assay or reagent 
Year Produced 2024 
Provided To Others? Yes  
Impact Pending 
URL https://github.com/fanbu1995/HIV-transmission-PoissonProcess
 
Description PANGEA-HIV 
Organisation University of Oxford
Department Big Data Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Methodological development for analysis of HIV deep-sequence data.
Collaborator Contribution This grant contributed to providing novel statistical methods for the analysis of infectious disease transmission sources from HIV deep-sequence data. The particular novelty of the contribution from this grant derives from statistical point process models that can analyse information on direction of transmission computationally more efficiently than previous approaches, due to avoiding a discretisation and full enumeration of the state space of the target variables.
Impact Pending - our methodological contribution was just published in 2024.
Start Year 2017
 
Title code for Inferring HIV transmission patterns from viral deep-sequence data via latent typed point processes 
Description The software provides the code for the Poisson process model developed for inferring transmission sources from deep sequence data 
Type Of Technology Software 
Year Produced 2024 
Open Source License? Yes  
Impact Pending 
URL https://github.com/fanbu1995/HIV-transmission-PoissonProcess
 
Description Real-time HIV molecular epidemiology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Use of HIV molecular epidemiology for public health surveillance, especially in relation to 1/ the application of HIV genomics for clinical management and public health surveillance; 2/ Bioinformatic approaches and tools for HIV genomics in public health surveillance; 3/ Ethical considerations in the use of HIV phylogenetics for public health surveillance; 4/ The role for HIV molecular epidemiology in informing public health policy for different settings; 5/ Governance of UK HIV Drug Resistance Database at UKHSA
Year(s) Of Engagement Activity 2024