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Christl A Donnelly

Publications and source records attributed to Christl A Donnelly.

4 recordsLinked to original sources

A decision-theoretic framework for uncertainty quantification in epidemiological modelling

Estimating, understanding, and communicating uncertainty is fundamental to statistical epidemiology, where model-based estimates regularly inform real-world decisions. However, sources of uncertainty are rarely formalised, and existing classifications are often defined inconsistently. This lack of structure hampers interpretation, model comparison, and targeted data collection. Connecting ideas from machine learning, information theory, experimental design, and health economics, we present a first-principles decision-theoretic framework that defines uncertainty as the expected loss incurred by making an estimate based on incomplete information, arguing that this is a highly useful and practically relevant definition for epidemiology. We show how reasoning about future data leads to a notion of expected uncertainty reduction, which induces formal definitions of reducible and irreducible uncertainty. We demonstrate our approach using a case study of SARS-CoV-2 wastewater surveillance in Aotearoa New Zealand, estimating the uncertainty reduction if wastewater surveillance were expanded to the full population. We then connect our framework to relevant literature from adjacent fields, showing how it unifies and extends many of these ideas and how it allows these ideas to be applied to a wider range of models. Altogether, our framework provides a foundation for more reliable, consistent, and policy-relevant uncertainty quantification in infectious disease epidemiology.

stat.ME↗

Phylo2Vec: a vector representation for binary trees

Binary phylogenetic trees inferred from biological data are central to understanding the shared history among evolutionary units. However, inferring the placement of latent nodes in a tree is computationally expensive. State-of-the-art methods rely on carefully designed heuristics for tree search, using different data structures for easy manipulation (e.g., classes in object-oriented programming languages) and readable representation of trees (e.g., Newick-format strings). Here, we present Phylo2Vec, a parsimonious encoding for phylogenetic trees that serves as a unified approach for both manipulating and representing phylogenetic trees. Phylo2Vec maps any binary tree with $n$ leaves to a unique integer vector of length $n-1$. The advantages of Phylo2Vec are fourfold: i) fast tree sampling, (ii) compressed tree representation compared to a Newick string, iii) quick and unambiguous verification if two binary trees are identical topologically, and iv) systematic ability to traverse tree space in very large or small jumps. As a proof of concept, we use Phylo2Vec for maximum likelihood inference on five real-world datasets and show that a simple hill-climbing-based optimisation scheme can efficiently traverse the vastness of tree space from a random to an optimal tree.

q-bio.PE↗

Leaping through tree space: continuous phylogenetic inference for rooted and unrooted trees

Phylogenetics is now fundamental in life sciences, providing insights into the earliest branches of life and the origins and spread of epidemics. However, finding suitable phylogenies from the vast space of possible trees remains challenging. To address this problem, for the first time, we perform both tree exploration and inference in a continuous space where the computation of gradients is possible. This continuous relaxation allows for major leaps across tree space in both rooted and unrooted trees, and is less susceptible to convergence to local minima. Our approach outperforms the current best methods for inference on unrooted trees and, in simulation, accurately infers the tree and root in ultrametric cases. The approach is effective in cases of empirical data with negligible amounts of data, which we demonstrate on the phylogeny of jawed vertebrates. Indeed, only a few genes with an ultrametric signal were generally sufficient for resolving the major lineages of vertebrates. Optimisation is possible via automatic differentiation and our method presents an effective way forwards for exploring the most difficult, data-deficient phylogenetic questions.

q-bio.PE↗

Key Questions for Modelling COVID-19 Exit Strategies

Combinations of intense non-pharmaceutical interventions ('lockdowns') were introduced in countries worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement lockdown exit strategies that allow restrictions to be relaxed while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, will allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. The roadmap requires a global collaborative effort from the scientific community and policy-makers, and is made up of three parts: i) improve estimation of key epidemiological parameters; ii) understand sources of heterogeneity in populations; iii) focus on requirements for data collection, particularly in Low-to-Middle-Income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.

q-bio.OT↗