Age K. Smilde

Florian Becker, Age K. Smilde, Evrim Acar

Computational phenotyping allows for unsupervised discovery of subgroups of patients as well as corresponding co-occurring medical conditions from electronic health records (EHR). Typically, EHR data contains demographic information, diagnoses and laboratory results. Discovering (novel) phenotypes has the potential to be of prognostic and therapeutic value. Providing medical practitioners with transparent and interpretable results is an important requirement and an essential part for advancing precision medicine. Low-rank data approximation methods such as matrix (e.g., non-negative matrix factorization) and tensor decompositions (e.g., CANDECOMP/PARAFAC) have demonstrated that they can provide such transparent and interpretable insights. Recent developments have adapted low-rank data approximation methods by incorporating different constraints and regularizations that facilitate interpretability further. In addition, they offer solutions for common challenges within EHR data such as high dimensionality, data sparsity and incompleteness. Especially extracting temporal phenotypes from longitudinal EHR has received much attention in recent years. In this paper, we provide a comprehensive review of low-rank approximation-based approaches for computational phenotyping. The existing literature is categorized into temporal vs. static phenotyping approaches based on matrix vs. tensor decompositions. Furthermore, we outline different approaches for the validation of phenotypes, i.e., the assessment of clinical significance.

Yipeng Song, Johan A. Westerhuis, Age K. Smilde

Multivariate binary data is becoming abundant in current biological research. Logistic principal component analysis (PCA) is one of the commonly used tools to explore the relationships inside a multivariate binary data set by exploiting the underlying low rank structure. We re-expressed the logistic PCA model based on the latent variable interpretation of the generalized linear model on binary data. The multivariate binary data set is assumed to be the sign observation of an unobserved quantitative data set, on which a low rank structure is assumed to exist. However, the standard logistic PCA model (using exact low rank constraint) is prone to overfitting, which could lead to divergence of some estimated parameters towards infinity. We propose to fit a logistic PCA model through non-convex singular value thresholding to alleviate the overfitting issue. An efficient Majorization-Minimization algorithm is implemented to fit the model and a missing value based cross validation (CV) procedure is introduced for the model selection. Our experiments on realistic simulations of imbalanced binary data and low signal to noise ratio show that the CV error based model selection procedure is successful in selecting the proposed model. Furthermore, the selected model demonstrates superior performance in recovering the underlying low rank structure compared to models with convex nuclear norm penalty and exact low rank constraint. A binary copy number aberration data set is used to illustrate the proposed methodology in practice.

Yipeng Song, Johan A. Westerhuis, Age K. Smilde

Multiple sets of measurements on the same objects obtained from different platforms may reflect partially complementary information of the studied system. The integrative analysis of such data sets not only provides us with the opportunity of a deeper understanding of the studied system, but also introduces some new statistical challenges. First, the separation of information that is common across all or some of the data sets, and the information that is specific to each data set is problematic. Furthermore, these data sets are often a mix of quantitative and discrete (binary or categorical) data types, while commonly used data fusion methods require all data sets to be quantitative. In this paper, we propose an exponential family simultaneous component analysis (ESCA) model to tackle the potential mixed data types problem of multiple data sets. In addition, a structured sparse pattern of the loading matrix is induced through a nearly unbiased group concave penalty to disentangle the global, local common and distinct information of the multiple data sets. A Majorization-Minimization based algorithm is derived to fit the proposed model. Analytic solutions are derived for updating all the parameters of the model in each iteration, and the algorithm will decrease the objective function in each iteration monotonically. For model selection, a missing value based cross validation procedure is implemented. The advantages of the proposed method in comparison with other approaches are assessed using comprehensive simulations as well as the analysis of real data from a chronic lymphocytic leukaemia (CLL) study. Availability: the codes to reproduce the results in this article are available at https://gitlab.com/uvabda.