Biology subjects

Bury, T.

Publications and source records attributed to Bury, T..

4 recordsLinked to original sources

bioRxiv2025

T-World: A highly general computational model of a human ventricular myocyte

Cardiovascular disease is the leading cause of death, demanding new tools to improve mechanistic understanding and overcome limitations of stem cell and animal-based research. We introduce T-World, a highly general virtual model of human ventricular cardiomyocyte suitable for multiscale studies. T-World shows comprehensive agreement with human physiology, from electrical activation to contraction, and is the first to replicate all key cellular mechanisms driving life-threatening arrhythmias. Extensively validated on unseen data, it demonstrates strong predictivity across applications and scales. Using T-World we revealed a likely sex-specific arrhythmia risk in females related to restitution properties, identified arrhythmia drivers in type 2 diabetes, and describe unexpected pro-arrhythmic role of NaV1.8 in heart failure. T-World demonstrates strong performance in predicting drug-induced arrhythmia risk and opens new opportunities for predicting and explaining drug efficacy, demonstrated by unpicking effects of mexiletine in Long QT syndrome 2. T-World is available as open-source code and an online app.

cell biology↗

bioRxiv2024

FateNet: an integration of dynamical systems and deep learning for cell fate prediction

Understanding cellular decision-making, particularly its timing and impact on the biological system such as tissue health and function, is a fundamental challenge in biology and medicine. Existing methods for inferring fate decisions and cellular state dynamics from single-cell RNA sequencing data lack precision regarding decision points and broader tissue implications. Addressing this gap, we present FateNet, a computational approach integrating dynamical systems theory and deep learning to probe the cell decision-making process using scRNA-seq data. By leveraging information about normal forms and scaling behavior near tipping pointscommon to many dynamical systems, FateNet accurately predicts cell decision occurrence and offers qualitative insights into the new state of the biological system. Also, through in-silico perturbation experiments, FateNet identifies key genes and pathways governing the differentiation process in hematopoiesis. Validated using different scRNA-seq data, FateNet emerges as a user-friendly and valuable tool for predicting critical points in biological processes, providing insights into complex trajectories.

bioinformatics↗

bioRxiv2021

Deep learning for early warning signals of regime shifts

Many natural systems exhibit regime shifts where slowly changing environmental conditions suddenly shift the system to a new and sometimes very different state. As the tipping point is approached, the dynamics of complex and varied systems all simplify down to a small number of possible normal forms that determine how the new regime will look. Indicators such as increasing lag-1 autocorrelation and variance provide generic early warning signals (EWS) by detecting how dynamics slow down near the tipping point. But they do not indicate what type of new regime will emerge. Here we develop a deep learning algorithm that can detect EWS in systems it was not explicitly trained on, by exploiting information about normal forms and scaling behaviour of dynamics near tipping points that are common to many dynamical systems. The algorithm detects EWS in 268 empirical and model time series from ecology, thermoacoustics, climatology, and epidemiology with much greater sensitivity and specificity than generic EWS. It can also predict the normal form that will characterize the oncoming regime shift. Such approaches can help humans better manage regime shifts. The algorithm also illustrates how a universe of possible models can be mined to recognize naturally-occurring tipping points.

ecology↗

bioRxiv2020

When conflicts get heated, so does the planet: social-climate dynamics under inequality

Climate dynamics are inextricably linked to processes in social systems that are highly unequal. This suggests a need for coupled social-climate models that capture pervasive real-world asymmetries in the population distribution of the consequences of anthropogenic climate change and climate (in)action. Here we develop a simple social-climate model with group structure to investigate how anthropogenic climate change and population heterogeneity co-evolve. We find that greater homophily and resource inequality cause an increase in the global peak temperature anomaly by as much as 0.7{degrees}C. Also, climate change can structure human populations by driving opinion polarization. Finally, climate mitigation achieved by reducing the cost of mitigation measures paid by individuals tends to be contingent upon socio-economic conditions, whereas policies that achieve communication between different strata of society show climate mitigation benefits across a broad socio-economic regime. We conclude that advancing climate change mitigation efforts can benefit from a social-climate systems perspective.

ecology↗