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.


Priors over Recurrent Continuous Time Processes

Neural Information Processing Systems

We introduce the Gamma-Exponential Process (GEP), a prior over a large family ofcontinuous time stochastic processes. A hierarchical version of this prior (HGEP; the Hierarchical GEP) yields a useful model for analyzing complex time series. Models based on HGEPs display many attractive properties: conjugacy, exchangeability and closed-form predictive distribution for the waiting times, and exact Gibbs updates for the time scale parameters. After establishing these properties, weshow how posterior inference can be carried efficiently using Particle MCMC methods [1]. This yields a MCMC algorithm that can resample entire sequences atomicallywhile avoiding the complications of introducing slice and stick auxiliary variables of the beam sampler [2]. We applied our model to the problem of estimating the disease progression in multiple sclerosis [3], and to RNA evolutionary modeling[4]. In both domains, we found that our model outperformed the standard rate matrix estimation approach.


Causal Inference through a Witness Protection Program

arXiv.org Machine Learning

One of the most fundamental problems in causal inference is the estimation of a causal effect when variables are confounded. This is difficult in an observational study, because one has no direct evidence that all confounders have been adjusted for. We introduce a novel approach for estimating causal effects that exploits observational conditional independencies to suggest "weak" paths in a unknown causal graph. The widely used faithfulness condition of Spirtes et al. is relaxed to allow for varying degrees of "path cancellations" that imply conditional independencies but do not rule out the existence of confounding causal paths. The outcome is a posterior distribution over bounds on the average causal effect via a linear programming approach and Bayesian inference. We claim this approach should be used in regular practice along with other default tools in observational studies.


Estimating the Size of a Large Network and its Communities from a Random Sample

Neural Information Processing Systems

Most real-world networks are too large to be measured or studied directly and there is substantial interest in estimating global network properties from smaller sub-samples. One of the most important global properties is the number of vertices/nodes in the network. Estimating the number of vertices in a large network is a major challenge in computer science, epidemiology, demography, and intelligence analysis. In this paper we consider a population random graph G = (V;E) from the stochastic block model (SBM) with K communities/blocks. A sample is obtained by randomly choosing a subset W and letting G(W) be the induced subgraph in G of the vertices in W. In addition to G(W), we observe the total degree of each sampled vertex and its block membership. Given this partial information, we propose an efficient PopULation Size Estimation algorithm, called PULSE, that accurately estimates the size of the whole population as well as the size of each community. To support our theoretical analysis, we perform an exhaustive set of experiments to study the effects of sample size, K, and SBM model parameters on the accuracy of the estimates. The experimental results also demonstrate that PULSE significantly outperforms a widely-used method called the network scale-up estimator in a wide variety of scenarios.


Solving the Empirical Bayes Normal Means Problem with Correlated Noise

arXiv.org Machine Learning

The Normal Means problem plays a fundamental role in many areas of modern high-dimensional statistics, both in theory and practice. And the Empirical Bayes (EB) approach to solving this problem has been shown to be highly effective, again both in theory and practice. However, almost all EB treatments of the Normal Means problem assume that the observations are independent. In practice correlations are ubiquitous in real-world applications, and these correlations can grossly distort EB estimates. Here, exploiting theory from Schwartzman (2010), we develop new EB methods for solving the Normal Means problem that take account of unknown correlations among observations. We provide practical software implementations of these methods, and illustrate them in the context of large-scale multiple testing problems and False Discovery Rate (FDR) control. In realistic numerical experiments our methods compare favorably with other commonly-used multiple testing methods.