Biology subjects

Wadkin, L. E.

Publications and source records attributed to Wadkin, L. E..

5 recordsLinked to original sources

bioRxiv2024

Unlocking precision: How corneal cell area analysis revolutionises post-transplant stem cell monitoring

The corneal epithelium is maintained by limbal stem cells (LSCs). Dysfunction of the LSCs, resulting from chemical and thermal burns, contact lens-related disease, congenial disorders, among other conditions, leads to limbal stem cell deficiency (LSCD), a sight-threatening condition. An effective treatment of LSCD, with 76% of patients reporting regained sight up to 24 months after the operation, consists of transplanting ex-vivo cultured LSCs from the patients other healthy eye (i.e. autologous) or donor (i.e. allogeneic) to the affected eye. The post-operative assessment of corneal recovery is crucial but relies on ponderous and generally subjective visual inspection of a large number of microscopic images of the corneal epithelial cells, relying on the personal experience of the practitioner to interpret imprecise, qualitative diagnostic criteria. From a unique library of 100,000 cornea cell images from 34 patients, we have randomly selected 10 individuals (3,668 images) to demonstrate that the frequency distribution of the epithelial cell areas is a sensitive diagnostic tool of the corneal epithelium status. After a successful operation the distribution of cell areas is rather flat, reflecting an anomalously wide range of cell areas. As the cornea recovers, the frequency distribution becomes narrower with high statistical confidence and eventually approaches that of the healthy cornea. The corneal epithelial cell shape is independent of the cornea status despite a widespread expectation that healthy cells have a hexagonal shape. We also show that the corneal epithelial cell area distribution and its variation with the depth within the cornea are specific to each patient. Significance StatementChemical and thermal cornea burns, contact-lens damage and hereditary factors, among other conditions, cause limbal stem cell deficiency (LSCD), a widespread sight-threatening condition. An efficient LSCD treatment involves a stem cell transplant from the patients other healthy eye, in unilateral cases, or a donor, in bilateral cases. Traditional post-operative cornea monitoring is laborious and often subjective as it relies on visual inspection of microscopy corneal epithelial images. We show that the distribution of epithelial cell areas is a sensitive LSCD diagnostic, evolving systematically to a healthy form after a successful treatment. We have developed computer algorithms to implement this quantitative, sensitive and precise approach which can radically improve the quality of both cornea monitoring in disease and response to treatment.

biophysics↗

bioRxiv2023

Estimating the reproduction number, R0, from agent-based models of tree disease spread

Tree populations worldwide are facing an unprecedented threat from a variety of tree diseases and invasive pests. Their spread, exacerbated by increasing globalisation and climate change, has an enormous environmental, economic and social impact. Computational agent-based models are a popular tool for describing and forecasting the spread of tree diseases due to their flexibility and ability to reveal collective behaviours. In this paper we present a versatile agentbased model with a Gaussian infectivity kernel to describe the spread of a generic tree disease through a synthetic treescape. We then explore several methods of calculating the basic reproduction number R0, a characteristic measurement of disease infectivity, defining the expected number of new infections resulting from one newly infected individual throughout their infectious period. It is a useful comparative summary parameter of a disease and can be used to explore the threshold dynamics of epidemics through mathematical models. We demonstrate several methods of estimating R0 through the agent-based model, including contact tracing, inferring the Kermack-McKendrick SIR model parameters using the linear noise approximation, and an analytical approximation. As an illustrative example, we then use the model and each of the methods to calculate estimates of R0 for the ash dieback epidemic in the UK.

ecology↗

bioRxiv2023

Quantifying invasive pest dynamics through inference of a two-node epidemic network model

Invasive woodland pests are having a substantial ecological, economic and social impact, harming biodiversity and ecosystem services. Mathematical modelling informed by Bayesian inference can deepen our understanding of the fundamental behaviours of invasive pests and provide predictive tools for forecasting the future spread. A key invasive pest of concern in the UK is the oak processionary moth (OPM). OPM was established in the UK in 2006, is harmful to both oak trees and humans, and its infestation area is continually expanding. Here, we use a computational inference scheme to estimate the parameters for a two-node network epidemic model to describe the temporal dynamics of OPM in two geographically neighbouring parks (Bushy Park and Richmond Park, London). We show the applicability of such a network model to describing invasive pest dynamics and our results suggest that the infestation within Richmond Park has largely driven the infestation within Bushy Park.

ecology↗

bioRxiv2021

Inference for epidemic models with time varying infection rates: tracking the dynamics of oak processionary moth in the UK

O_LIInvasive pests pose a great threat to forest, woodland and urban tree ecosystems. The oak processionary moth (OPM) is a destructive pest of oak trees, first reported in the UK in 2006. Despite great efforts to contain the outbreak within the original infested area of South-East England, OPM continues to spread. C_LIO_LIHere we analyse data of the numbers of OPM nests removed each year from two parks in London between 2013 and 2020. Using a state-of-the-art Bayesian inference scheme we estimate the parameters for a stochastic compartmental SIR (susceptible, infested, removed) model with a time varying infestation rate to describe the spread of OPM. C_LIO_LIWe find that the infestation rate and subsequent basic reproduction number have remained constant since 2013 (with R0 between one and two). This shows further controls must be taken to reduce R0 below one and stop the advance of OPM into other areas of England. C_LIO_LISynthesis. Our findings demonstrate the applicability of the SIR model to describing OPM spread and show that further controls are needed to reduce the infestation rate. The proposed statistical methodology is a powerful tool to explore the nature of a time varying infestation rate, applicable to other partially observed time series epidemic data. C_LI

ecology↗

bioRxiv2020

Spatio-temporal analyses of OCT4 expression and fate transitions in human embryonic stem cells

OCT4 is one of the transcription factors required to maintain an undifferentiated state in human embryonic stem cells (hESCs). Thus, it is crucial to understand how OCT4 transcription is regulated both at the single-cell and colony level. Here we analyse the changes of OCT4-mCherry intensity expression in hESCs in the presence and absence of the BMP4 morphogenetic protein. We show that OCT4 expression is dynamic, reaching a maximum response 10 h after BMP4 treatment. We obtain the stationary probability distributions that govern the hESCs transitions amongst the different cell states in the presence/absence of BMP4 and establish the times at which the hESCs, that lead to differentiated and pluripotent cells, cluster in the colony. Furthermore, by quantifying the similarities between the OCT4 expression amongst neighbouring hESCs, we show that hESCs express, on average, similar values in their local neighbourhood within the first two days of the experiment and before BMP4 treatment. These results are relevant for the development of mathematical and computational models of adherent hESC colonies.

biophysics↗