Probabilistic Event Cascades for Alzheimer's disease

Neural Information Processing Systems

Accurate and detailed models of the progression of neurodegenerative diseases such as Alzheimer's (AD) are crucially important for reliable early diagnosis and the determination and deployment of effective treatments. In this paper, we introduce the ALPACA (Alzheimer's disease Probabilistic Cascades) model, a generative model linking latent Alzheimer's progression dynamics to observable biomarker data. In contrast with previous works which model disease progression as a fixed ordering of events, we explicitly model the variability over such orderings among patients which is more realistic, particularly for highly detailed disease progression models. We describe efficient learning algorithms for ALPACA and discuss promising experimental results on a real cohort of Alzheimer's patients from the Alzheimer's Disease Neuroimaging Initiative.

Learning From What You Don't Observe Artificial Intelligence

The process of diagnosis involves learning about the state of a system from various observations of symptoms or findings about the system. Sophisticated Bayesian (and other) algorithms have been developed to revise and maintain beliefs about the system as observations are made. Nonetheless, diagnostic models have tended to ignore some common sense reasoning exploited by human diagnosticians; In particular, one can learn from which observations have not been made, in the spirit of conversational implicature. There are two concepts that we describe to extract information from the observations not made. First, some symptoms, if present, are more likely to be reported before others. Second, most human diagnosticians and expert systems are economical in their data-gathering, searching first where they are more likely to find symptoms present. Thus, there is a desirable bias toward reporting symptoms that are present. We develop a simple model for these concepts that can significantly improve diagnostic inference.

A Bayesian Nonparametric Method for Clustering Imputation, and Forecasting in Multivariate Time Series Machine Learning

This article proposes a Bayesian nonparametric method for forecasting, imputation, and clustering in sparsely observed, multivariate time series. The method is appropriate for jointly modeling hundreds of time series with widely varying, non-stationary dynamics. Given a collection of $N$ time series, the Bayesian model first partitions them into independent clusters using a Chinese restaurant process prior. Within a cluster, all time series are modeled jointly using a novel "temporally-coupled" extension of the Chinese restaurant process mixture. Markov chain Monte Carlo techniques are used to obtain samples from the posterior distribution, which are then used to form predictive inferences. We apply the technique to challenging prediction and imputation tasks using seasonal flu data from the US Center for Disease Control and Prevention, demonstrating competitive imputation performance and improved forecasting accuracy as compared to several state-of-the art baselines. We also show that the model discovers interpretable clusters in datasets with hundreds of time series using macroeconomic data from the Gapminder Foundation.

Sequential Dirichlet Process Mixtures of Multivariate Skew t-distributions for Model-based Clustering of Flow Cytometry Data Machine Learning

Flow cytometry is a high-throughput technology used to quantify multiple surface and intracellular markers at the level of a single cell. This enables to identify cell sub-types, and to determine their relative proportions. Improvements of this technology allow to describe millions of individual cells from a blood sample using multiple markers. This results in high-dimensional datasets, whose manual analysis is highly time-consuming and poorly reproducible. While several methods have been developed to perform automatic recognition of cell populations, most of them treat and analyze each sample independently. However, in practice, individual samples are rarely independent (e.g. longitudinal studies). Here, we propose to use a Bayesian nonparametric approach with Dirichlet process mixture (DPM) of multivariate skew $t$-distributions to perform model based clustering of flow-cytometry data. DPM models directly estimate the number of cell populations from the data, avoiding model selection issues, and skew $t$-distributions provides robustness to outliers and non-elliptical shape of cell populations. To accommodate repeated measurements, we propose a sequential strategy relying on a parametric approximation of the posterior. We illustrate the good performance of our method on simulated data, on an experimental benchmark dataset, and on new longitudinal data from the DALIA-1 trial which evaluates a therapeutic vaccine against HIV. On the benchmark dataset, the sequential strategy outperforms all other methods evaluated, and similarly, leads to improved performance on the DALIA-1 data. We have made the method available for the community in the R package NPflow.

On the complexity of logistic regression models Machine Learning

We investigate the complexity of logistic regression models which is defined by counting the number of indistinguishable distributions that the model can represent (Balasubramanian, 1997). We find that the complexity of logistic models with binary inputs does not only depend on the number of parameters but also on the distribution of inputs in a non-trivial way which standard treatments of complexity do not address. In particular, we observe that correlations among inputs induce effective dependencies among parameters thus constraining the model and, consequently, reducing its complexity. We derive simple relations for the upper and lower bounds of the complexity. Furthermore, we show analytically that, defining the model parameters on a finite support rather than the entire axis, decreases the complexity in a manner that critically depends on the size of the domain. Based on our findings, we propose a novel model selection criterion which takes into account the entropy of the input distribution. We test our proposal on the problem of selecting the input variables of a logistic regression model in a Bayesian Model Selection framework. In our numerical tests, we find that, while the reconstruction errors of standard model selection approaches (AIC, BIC, $\ell_1$ regularization) strongly depend on the sparsity of the ground truth, the reconstruction error of our method is always close to the minimum in all conditions of sparsity, data size and strength of input correlations. Finally, we observe that, when considering categorical instead of binary inputs, in a simple and mathematically tractable case, the contribution of the alphabet size to the complexity is very small compared to that of parameter space dimension. We further explore the issue by analysing the dataset of the "13 keys to the White House" which is a method for forecasting the outcomes of US presidential elections.