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John Aston

Publications and source records attributed to John Aston.

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SurvSurf: a partially monotonic neural network for first-hitting time prediction of intermittently observed discrete and continuous sequential events

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.

stat.ML

On Krylov Methods for Large Scale CBCT Reconstruction

Krylov subspace methods are a powerful family of iterative solvers for linear systems of equations, which are commonly used for inverse problems due to their intrinsic regularization properties. Moreover, these methods are naturally suited to solve large-scale problems, as they only require matrix-vector products with the system matrix (and its adjoint) to compute approximate solutions, and they display a very fast convergence. Even if this class of methods has been widely researched and studied in the numerical linear algebra community, its use in applied medical physics and applied engineering is still very limited. e.g. in realistic large-scale Computed Tomography (CT) problems, and more specifically in Cone Beam CT (CBCT). This work attempts to breach this gap by providing a general framework for the most relevant Krylov subspace methods applied to 3D CT problems, including the most well-known Krylov solvers for non-square systems (CGLS, LSQR, LSMR), possibly in combination with Tikhonov regularization, and methods that incorporate total variation (TV) regularization. This is provided within an open source framework: the Tomographic Iterative GPU-based Reconstruction (TIGRE) toolbox, with the idea of promoting accessibility and reproducibility of the results for the algorithms presented. Finally, numerical results in synthetic and real-world 3D CT applications (medical CBCT and μ-CT datasets) are provided to showcase and compare the different Krylov subspace methods presented in the paper, as well as their suitability for different kinds of problems.

math.NA

Hidden Talents of the Variational Autoencoder

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.

cs.LG

Monotonicity of Fitness Landscapes and Mutation Rate Control

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.

q-bio.PE

A Variational Model Dedicated to Joint Segmentation, Registration and Atlas Generation for Shape Analysis

In medical image analysis, constructing an atlas, i.e. a mean representative of an ensemble of images, is a critical task for practitioners to estimate variability of shapes inside a population, and to characterise and understand how structural shape changes have an impact on health. This involves identifying significant shape constituents of a set of images, a process called segmentation, and mapping this group of images to an unknown mean image, a task called registration, making a statistical analysis of the image population possible. To achieve this goal, we propose treating these operations jointly to leverage their positive mutual influence, in a hyperelasticity setting, by viewing the shapes to be matched as Ogden materials. The approach is complemented by novel hard constraints on the $L^\infty$ norm of both the Jacobian and its inverse, ensuring that the deformation is a bi-Lipschitz homeomorphism. Segmentation is based on the Potts model, which allows for a partition into more than two regions, i.e. more than one shape. The connection to the registration problem is ensured by the dissimilarity measure that aims to align the segmented shapes. A representation of the deformation field in a linear space equipped with a scalar product is then computed in order to perform a geometry-driven Principal Component Analysis (PCA) and to extract the main modes of variations inside the image population. Theoretical results emphasizing the mathematical soundness of the model are provided, among which existence of minimisers, analysis of a numerical method of resolution, asymptotic results and a PCA analysis, as well as numerical simulations demonstrating the ability of the modeling to produce an atlas exhibiting sharp edges, high contrast and a consistent shape.

math.NA

Accurate autocorrelation modeling substantially improves fMRI reliability

Given the recent controversies in some neuroimaging statistical methods, we compare the most frequently used functional Magnetic Resonance Imaging (fMRI) analysis packages: AFNI, FSL and SPM, with regard to temporal autocorrelation modeling. This process, sometimes known as pre-whitening, is conducted in virtually all task fMRI studies. We employ eleven datasets containing 980 scans corresponding to different fMRI protocols and subject populations. Though autocorrelation modeling in AFNI is not perfect, its performance is much higher than the performance of autocorrelation modeling in FSL and SPM. The residual autocorrelated noise in FSL and SPM leads to heavily confounded first level results, particularly for low-frequency experimental designs. Our results show superior performance of SPM's alternative pre-whitening: FAST, over SPM's default. The reliability of task fMRI studies would increase with more accurate autocorrelation modeling. Furthermore, reliability could increase if the packages provided diagnostic plots. This way the investigator would be aware of pre-whitening problems.

q-bio.QM

Divide-and-Conquer with Sequential Monte Carlo

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.

stat.CO