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Sandra Safo

Publications and source records attributed to Sandra Safo.

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Sparse Functional Singular Value Decomposition for Biclustering and Triclustering Longitudinal Data

Identifying subtypes of complex conditions, such as Inflammatory Bowel Disease (IBD), often requires capturing latent patterns in longitudinal omics data. However, these data are typically high-dimensional, sparsely sampled, and irregularly observed over time, posing substantial challenges for conventional (bi)clustering and functional data analysis methods. We propose Tri-SfSVD, a unified sparse functional Singular Value Decomposition framework for discovering biclusters and triclusters in longitudinal data. Unlike existing functional biclustering methods that rely on ad hoc imputation or enforce restrictive shape-homogeneity assumptions, Tri-SfSVD integrates continuous trajectory estimation with simultaneous subject, feature, and temporal selection within a single optimization framework. By imposing sparse penalties across subjects, variables, and temporal subregions, the proposed method works directly on observed data to uncover localized structures at the subject, subject-feature, and subject-feature-time levels. Extensive simulations demonstrate that Tri-SfSVD outperforms existing approaches in high-dimensional settings. Applied to IBD multi-omics data, the method identified three biclusters linking sample clusters with distinct IBD-related clinical characteristics to microbial pathway groups associated with specific bacterial taxa, providing interpretable subject-pathway associations for characterizing disease heterogeneity. Applied to multi-channel EEG data, the method identified three triclusters linking sample clusters with distinct alcohol-related phenotypes to localized brain activity patterns, including subgroup differences separated by temporal subregions within the same spatial region.

stat.ML

A Bayesian Integrative Mixed Modeling Framework for Analysis of the Adolescent Brain and Cognitive Development Study

Integrating high-dimensional, heterogeneous data from multi-site cohort studies with complex hierarchical structures poses significant feature selection and prediction challenges. We extend the Bayesian Integrative Analysis and Prediction (BIP) framework to enable simultaneous feature selection and outcome modeling in data of nested hierarchical structure. We apply the proposed Bayesian Integrative Mixed Modeling (BIPmixed) framework to the Adolescent Brain Cognitive Development (ABCD) Study, leveraging multi-view data, including structural and functional MRI and early life adversity (ELA) metrics, to identify relevant features and predict the behavioral outcome. BIPmixed incorporates 2-level nested random effects, to enhance interpretability and make predictions in hierarchical data settings. Simulation studies illustrate BIPmixed's robustness in distinct random effect settings, highlighting its use for complex study designs. Our findings suggest that BIPmixed effectively integrates multi-view data while accounting for nested sampling, making it a valuable tool for analyzing large-scale studies with hierarchical data.

stat.ME

Sample size determination for training cancer classifiers from microarray and RNA-seq data

The objective of many high-dimensional microarray and RNA-seq studies is to develop a classifier of cancer patients based on characteristics of their disease. The germinal center B-cell (GCB) classifier study in lymphoma and the National Cancer Institute's Director's Challenge lung (DC-lung) study are two examples. In recent years, such classifiers are often developed using regularized regression, such as the lasso. A critical question is whether a better classifier can be developed from a larger training set size and, if so, how large the training set should be. This paper examines these two questions using an existing sample size method and a novel sample size method developed here specifically for lasso logistic regression. Both methods are based on pilot data. We reexamine the lymphoma and lung cancer data sets to evaluate the sample sizes, and use resampling to assess the estimation methods. We also study application to an RNA-seq data set. We find that it is feasible to estimate sample size for regularized logistic regression if an adequate pilot data set exists. The GCB and the DC-lung data sets appear adequate, under specific assumptions. Existing human RNA-seq data sets are by and large inadequate, and cannot be used as pilot data. Pilot RNA-seq data can be simulated, and the methods in this paper can be used for sample size estimation. A MATLAB program is made available.

stat.AP