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Existing studies consider Alzheimers disease (AD) a comorbidity of epilepsy, but also recognize epilepsy to occur more frequently in patients with AD than those without. The goal of this paper is to understand the relationship between epilepsy and AD by studying causal relations among subgroups of epilepsy patients. We develop an approach combining representation learning with tensor factorization to provide an in-depth analysis of the risk factors among epilepsy patients for AD. An epilepsy-AD cohort of ~600,000 patients were extracted from Cerner Health Facts data (50M patients). Our experimental results not only suggested a causal relationship between epilepsy and later onset of AD ( p = 1.92e-51), but also identified five epilepsy subgroups with distinct phenotypic patterns leading to AD. While such findings are preliminary, the proposed method combining representation learning with tensor factorization seems to be an effective approach for risk factor analysis.
Uncovering the heterogeneity in the disease progression of Alzheimers is a key factor to disease understanding and treatment development, so that interventions can be tailored to target the subgroups that will benefit most from the treatment, which is an important goal of precision medicine. However, in practice, one top methodological challenge hindering the heterogeneity investigation is that the true subgroup membership of each individual is often unknown. In this article, we aim to identify latent subgroups of individuals who share a common disorder progress over time, to predict latent subgroup memberships, and to estimate and infer the heterogeneous trajectories among the subgroups. To achieve these goals, we apply a concave fusion learning method proposed in Ma and Huang (2017) and Ma et al. (2019) to conduct subgroup analysis for longitudinal trajectories of the Alzheimers disease data. The heterogeneous trajectories are represented by subject-specific unknown functions which are approximated by B-splines. The concave fusion method can simultaneously estimate the spline coefficients and merge them together for the subjects belonging to the same subgroup to automatically identify subgroups and recover the heterogeneous trajectories. The resulting estimator of the disease trajectory of each subgroup is supported by an asymptotic distribution. It provides a sound theoretical basis for further conducting statistical inference in subgroup analysis..
Nonnegative Matrix Factorization (NMF) aims to factorize a matrix into two optimized nonnegative matrices and has been widely used for unsupervised learning tasks such as product recommendation based on a rating matrix. However, although networks between nodes with the same nature exist, standard NMF overlooks them, e.g., the social network between users. This problem leads to comparatively low recommendation accuracy because these networks are also reflections of the nature of the nodes, such as the preferences of users in a social network. Also, social networks, as complex networks, have many different structures. Each structure is a composition of links between nodes and reflects the nature of nodes, so retaining the different network structures will lead to differences in recommendation performance. To investigate the impact of these network structures on the factorization, this paper proposes four multi-level network factorization algorithms based on the standard NMF, which integrates the vertical network (e.g., rating matrix) with the structures of horizontal network (e.g., user social network). These algorithms are carefully designed with corresponding convergence proofs to retain four desired network structures. Experiments on synthetic data show that the proposed algorithms are able to preserve the desired network structures as designed. Experiments on real-world data show that considering the horizontal networks improves the accuracy of document clustering and recommendation with standard NMF, and various structures show their differences in performance on these two tasks. These results can be directly used in document clustering and recommendation systems.
Lyme disease is an infectious disease that is caused by a bacterium called Borrelia burgdorferi sensu stricto. In the United States, Lyme disease is one of the most common infectious diseases. The major endemic areas of the disease are New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central. Virginia is on the front-line of the diseases diffusion from the northeast to the south. One of the research objectives for the infectious disease community is to identify environmental and economic variables that are associated with the emergence of Lyme disease. In this paper, we use a spatial Poisson regression model to link the spatial disease counts and environmental and economic variables, and develop a spatial variable selection procedure to effectively identify important factors by using an adaptive elastic net penalty. The proposed methods can automatically select important covariates, while adjusting for possible spatial correlations of disease counts. The performance of the proposed method is studied and compared with existing methods via a comprehensive simulation study. We apply the developed variable selection methods to the Virginia Lyme disease data and identify important variables that are new to the literature. Supplementary materials for this paper are available online.
Multi-view data refers to a setting where features are divided into feature sets, for example because they correspond to different sources. Stacked penalized logistic regression (StaPLR) is a recently introduced method that can be used for classification and automatically selecting the views that are most important for prediction. We show how this method can easily be extended to a setting where the data has a hierarchical multi-view structure. We apply StaPLR to Alzheimers disease classification where different MRI measures have been calculated from three scan types: structural MRI, diffusion-weighted MRI, and resting-state fMRI. StaPLR can identify which scan types and which MRI measures are most important for classification, and it outperforms elastic net regression in classification performance.
The current state-of-the-art deep neural networks (DNNs) for Alzheimers Disease diagnosis use different biomarker combinations to classify patients, but do not allow extracting knowledge about the interactions of biomarkers. However, to improve our understanding of the disease, it is paramount to extract such knowledge from the learned model. In this paper, we propose a Deep Factorization Machine model that combines the ability of DNNs to learn complex relationships and the ease of interpretability of a linear model. The proposed model has three parts: (i) an embedding layer to deal with sparse categorical data, (ii) a Factorization Machine to efficiently learn pairwise interactions, and (iii) a DNN to implicitly model higher order interactions. In our experiments on data from the Alzheimers Disease Neuroimaging Initiative, we demonstrate that our proposed model classifies cognitive normal, mild cognitive impaired, and demented patients more accurately than competing models. In addition, we show that valuable knowledge about the interactions among biomarkers can be obtained.