John A. D. Aston

Tolou Shadbahr, Michael Roberts, Jan Stanczuk et al.

Classifying samples in incomplete datasets is a common aim for machine learning practitioners, but is non-trivial. Missing data is found in most real-world datasets and these missing values are typically imputed using established methods, followed by classification of the now complete, imputed, samples. The focus of the machine learning researcher is then to optimise the downstream classification performance. In this study, we highlight that it is imperative to consider the quality of the imputation. We demonstrate how the commonly used measures for assessing quality are flawed and propose a new class of discrepancy scores which focus on how well the method recreates the overall distribution of the data. To conclude, we highlight the compromised interpretability of classifier models trained using poorly imputed data.

Fan Zhang, Daniel Kreuter, Yichen Chen et al.

For healthcare datasets, it is often not possible to combine data samples from multiple sites due to ethical, privacy or logistical concerns. Federated learning allows for the utilisation of powerful machine learning algorithms without requiring the pooling of data. Healthcare data has many simultaneous challenges which require new methodologies to address, such as highly-siloed data, class imbalance, missing data, distribution shifts and non-standardised variables. Federated learning adds significant methodological complexity to conventional centralised machine learning, requiring distributed optimisation, communication between nodes, aggregation of models and redistribution of models. In this systematic review, we consider all papers on Scopus that were published between January 2015 and February 2023 and which describe new federated learning methodologies for addressing challenges with healthcare data. We performed a detailed review of the 89 papers which fulfilled these criteria. Significant systemic issues were identified throughout the literature which compromise the methodologies in many of the papers reviewed. We give detailed recommendations to help improve the quality of the methodology development for federated learning in healthcare.

Sören Dittmer, Michael Roberts, Julian Gilbey et al.

In this perspective, we argue that despite the democratization of powerful tools for data science and machine learning over the last decade, developing the code for a trustworthy and effective data science system (DSS) is getting harder. Perverse incentives and a lack of widespread software engineering (SE) skills are among many root causes we identify that naturally give rise to the current systemic crisis in reproducibility of DSSs. We analyze why SE and building large complex systems is, in general, hard. Based on these insights, we identify how SE addresses those difficulties and how we can apply and generalize SE methods to construct DSSs that are fit for purpose. We advocate two key development philosophies, namely that one should incrementally grow -- not biphasically plan and build -- DSSs, and one should always employ two types of feedback loops during development: one which tests the code's correctness and another that evaluates the code's efficacy.

Sören Dittmer, Michael Roberts, Jacobus Preller et al.

Survival analysis is an integral part of the statistical toolbox. However, while most domains of classical statistics have embraced deep learning, survival analysis only recently gained some minor attention from the deep learning community. This recent development is likely in part motivated by the COVID-19 pandemic. We aim to provide the tools needed to fully harness the potential of survival analysis in deep learning. On the one hand, we discuss how survival analysis connects to classification and regression. On the other hand, we provide technical tools. We provide a new loss function, evaluation metrics, and the first universal approximating network that provably produces survival curves without numeric integration. We show that the loss function and model outperform other approaches using a large numerical study.

Daniel Kreuter, Samuel Tull, Julian Gilbey et al.

Clinical data is often affected by clinically irrelevant factors such as discrepancies between measurement devices or differing processing methods between sites. In the field of machine learning (ML), these factors are known as domains and the distribution differences they cause in the data are known as domain shifts. ML models trained using data from one domain often perform poorly when applied to data from another domain, potentially leading to wrong predictions. As such, developing machine learning models that can generalise well across multiple domains is a challenging yet essential task in the successful application of ML in clinical practice. In this paper, we propose a novel disentangled autoencoder (Dis-AE) neural network architecture that can learn domain-invariant data representations for multi-label classification of medical measurements even when the data is influenced by multiple interacting domain shifts at once. The model utilises adversarial training to produce data representations from which the domain can no longer be determined. We evaluate the model's domain generalisation capabilities on synthetic datasets and full blood count (FBC) data from blood donors as well as primary and secondary care patients, showing that Dis-AE improves model generalisation on multiple domains simultaneously while preserving clinically relevant information.

Louis G. Christie, John A. D. Aston

Invariant and equivariant models incorporate the symmetry of an object to be estimated (here non-parametric regression functions $f : \mathcal{X} \rightarrow \mathbb{R}$). These models perform better (with respect to $L^2$ loss) and are increasingly being used in practice, but encounter problems when the symmetry is falsely assumed. In this paper we present a framework for testing for $G$-equivariance for any semi-group $G$. This will give confidence to the use of such models when the symmetry is not known a priori. These tests are independent of the model and are computationally quick, so can be easily used before model fitting to test their validity.

Yichen Kelly Chen, Sören Dittmer, Kinga Bernatowicz et al.

We propose a neural-network based survival model (SurvSurf) specifically designed for direct and simultaneous probabilistic prediction of the first hitting time of sequential events from baseline. Unlike existing models, SurvSurf is theoretically guaranteed to never violate the monotonic relationship between the cumulative incidence functions of sequential events, while allowing nonlinear influence from predictors. It also incorporates implicit truths for unobserved intermediate events in model fitting, and supports both discrete and continuous time and events. We also identified a variant of the Integrated Brier Score (IBS) that showed robust correlation with the mean squared error (MSE) between the true and predicted probabilities by accounting for implied truths about the missing intermediate events. We demonstrated the superiority of SurvSurf compared to modern and traditional predictive survival models in two simulated datasets and two real-world datasets, using MSE, the more robust IBS and by measuring the extent of monotonicity violation.

Bin Dai, Yu Wang, John Aston et al.

Variational autoencoders (VAE) represent a popular, flexible form of deep generative model that can be stochastically fit to samples from a given random process using an information-theoretic variational bound on the true underlying distribution. Once so-obtained, the model can be putatively used to generate new samples from this distribution, or to provide a low-dimensional latent representation of existing samples. While quite effective in numerous application domains, certain important mechanisms which govern the behavior of the VAE are obfuscated by the intractable integrals and resulting stochastic approximations involved. Moreover, as a highly non-convex model, it remains unclear exactly how minima of the underlying energy relate to original design purposes. We attempt to better quantify these issues by analyzing a series of tractable special cases of increasing complexity. In doing so, we unveil interesting connections with more traditional dimensionality reduction models, as well as an intrinsic yet underappreciated propensity for robustly dismissing sparse outliers when estimating latent manifolds. With respect to the latter, we demonstrate that the VAE can be viewed as the natural evolution of recent robust PCA models, capable of learning nonlinear manifolds of unknown dimension obscured by gross corruptions.

Fredrik Lindsten, Adam M. Johansen, Christian A. Naesseth et al.

We propose a novel class of Sequential Monte Carlo (SMC) algorithms, appropriate for inference in probabilistic graphical models. This class of algorithms adopts a divide-and-conquer approach based upon an auxiliary tree-structured decomposition of the model of interest, turning the overall inferential task into a collection of recursively solved sub-problems. The proposed method is applicable to a broad class of probabilistic graphical models, including models with loops. Unlike a standard SMC sampler, the proposed Divide-and-Conquer SMC employs multiple independent populations of weighted particles, which are resampled, merged, and propagated as the method progresses. We illustrate empirically that this approach can outperform standard methods in terms of the accuracy of the posterior expectation and marginal likelihood approximations. Divide-and-Conquer SMC also opens up novel parallel implementation options and the possibility of concentrating the computational effort on the most challenging sub-problems. We demonstrate its performance on a Markov random field and on a hierarchical logistic regression problem.

Roman V. Belavkin, Alastair Channon, Elizabeth Aston et al.

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms.