Searcharxiv⌕ Search

arXiv subjects

Sandra E. Safo

Publications and source records attributed to Sandra E. Safo.

13 recordsLinked to original sources

BayesClint: Bayesian Multi-Scale Clustering and Multi-Sample Integration With Feature Selection for Spatial Transcriptomics Data

Recent advances in spatial transcriptomics have enabled researchers to profile gene expression at the single-cell spatial resolution, often for multiple tissue samples in a single study. This high-dimensional molecular profile for each cell can be used to sort cells into cell types with distinct functions, or segment the tissue into biologically relevant spatial domains. Although many non-spatial and spatial clustering methods have been developed to cluster these cells into cell types or spatial domains, most have two main limitations: first, they perform dimension reduction and clustering separately; second, they cluster cells at a single scale, rather than treating cell type and spatial domain clustering as distinct tasks at two different scales. To overcome these limitations, we propose BayesClint, a Bayesian method that simultaneously performs factor analysis and spatial clustering on multiple samples, where the clustering is done jointly at the single-cell and tissue regional scale. To increase interpretability, we employ a feature selection mechanism within the estimation of the sparse factor loadings matrix, which detects active genes and differentially expressed genes that discriminate between cell type clusters. We illustrate the advantages of the method over alternative state-of-the-art approaches through simulation studies and two real data applications.

stat.ME↗

Multivariate Functional Linear Discriminant Analysis: An Application to Inflammatory Bowel Disease Classification

Inflammatory Bowel Disease (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC), presents significant public health challenges due to its complex etiology. Motivated by the IBD study of the Integrative Human Microbiome Project, our objective is to identify microbial pathways that distinguish between CD, UC and non-IBD over time. Most current research relies on simplistic analyses that examine one variable or time point at a time, or address binary classification problems, limiting our understanding of the dynamic interactions within the microbiome over time. To address these limitations, we develop a novel functional data analysis approach for discriminant analysis of multivariate functional data that can effectively handle multiple high-dimensional predictors, sparse time points, and categorical outcomes. Our method seeks linear combinations of functions (i.e., discriminant functions) that maximize separation between two or more groups over time. We impose a sparsity-inducing penalty when estimating the discriminant functions, allowing us to identify relevant discriminating variables over time. Applications of our method to the motivating data identified microbial features related to mucin degradation, amino acid metabolism, and peptidoglycan recognition, which are implicated in the progression and development of IBD. Furthermore, our method highlighted the role of multiple vitamin B deficiencies in the context of IBD. By moving beyond traditional analytical frameworks, our innovative approach holds the potential for uncovering clinically meaningful discoveries in IBD research.

stat.AP↗

Supervised Integrative Biclustering with applications to Alzheimer's Disease

Multiple types or views of data (e.g. genetics, proteomics) measured on the same set of individuals are now popularly generated in many biomedical studies. A particular interest might be the detection of sample subgroups (e.g. subtypes of disease) characterized by specific groups of variables. Biclustering methods are well-suited for this problem since they can group samples and variables simultaneously. However, most existing biclustering methods cannot guarantee that the detected sample clusters are clinically meaningful and related to a clinical outcome because they independently identify biclusters and associate sample clusters with a clinical outcome. Additionally, these methods have been developed for continuous data when integrating data from different views and do not allow for a mixture of data distributions. We propose a new formulation of biclustering and prediction method for multi-view data from different distributions that enhances our ability to identify clinically meaningful biclusters by incorporating a clinical outcome. Sample clusters are defined based on an adaptively chosen subset of variables and their association with a clinical outcome. We use extensive simulations to showcase the effectiveness of our proposed method in comparison to existing methods. Real-world applications using lipidomics, imaging, and cognitive data on Alzheimer's disease(AD) identified biclusters with significant cognitive differences that other methods missed. The distinct lipid categories and brain regions characterizing the biclusters suggest potential new insights into pathology of AD.

stat.ME↗

A deep learning pipeline for cross-sectional and longitudinal multiview data integration

Biomedical research now commonly integrates diverse data types or views from the same individuals to better understand the pathobiology of complex diseases, but the challenge lies in meaningfully integrating these diverse views. Existing methods often require the same type of data from all views (cross-sectional data only or longitudinal data only) or do not consider any class outcome in the integration method, presenting limitations. To overcome these limitations, we have developed a pipeline that harnesses the power of statistical and deep learning methods to integrate cross-sectional and longitudinal data from multiple sources. Additionally, it identifies key variables contributing to the association between views and the separation among classes, providing deeper biological insights. This pipeline includes variable selection/ranking using linear and nonlinear methods, feature extraction using functional principal component analysis and Euler characteristics, and joint integration and classification using dense feed-forward networks and recurrent neural networks. We applied this pipeline to cross-sectional and longitudinal multi-omics data (metagenomics, transcriptomics, and metabolomics) from an inflammatory bowel disease (IBD) study and we identified microbial pathways, metabolites, and genes that discriminate by IBD status, providing information on the etiology of IBD. We conducted simulations to compare the two feature extraction methods. The proposed pipeline is available from the following GitHub repository: https://github.com/lasandrall/DeepIDA-GRU.

cs.LG↗

mvlearnR and Shiny App for multiview learning

The package mvlearnR and accompanying Shiny App is intended for integrating data from multiple sources or views or modalities (e.g. genomics, proteomics, clinical and demographic data). Most existing software packages for multiview learning are decentralized and offer limited capabilities, making it difficult for users to perform comprehensive integrative analysis. The new package wraps statistical and machine learning methods and graphical tools, providing a convenient and easy data integration workflow. For users with limited programming language, we provide a Shiny Application to facilitate data integration anywhere and on any device. The methods have potential to offer deeper insights into complex disease mechanisms. Availability and Implementation: mvlearnR is available from the following GitHub repository: https://github.com/lasandrall/mvlearnR. The web application is hosted on shinyapps.io and available at: https://multi-viewlearn.shinyapps.io/MultiView_Modeling/

q-bio.GN↗

Scalable Randomized Kernel Methods for Multiview Data Integration and Prediction

We develop scalable randomized kernel methods for jointly associating data from multiple sources and simultaneously predicting an outcome or classifying a unit into one of two or more classes. The proposed methods model nonlinear relationships in multiview data together with predicting a clinical outcome and are capable of identifying variables or groups of variables that best contribute to the relationships among the views. We use the idea that random Fourier bases can approximate shift-invariant kernel functions to construct nonlinear mappings of each view and we use these mappings and the outcome variable to learn view-independent low-dimensional representations. Through simulation studies, we show that the proposed methods outperform several other linear and nonlinear methods for multiview data integration. When the proposed methods were applied to gene expression, metabolomics, proteomics, and lipidomics data pertaining to COVID-19, we identified several molecular signatures forCOVID-19 status and severity. Results from our real data application and simulations with small sample sizes suggest that the proposed methods may be useful for small sample size problems. Availability: Our algorithms are implemented in Pytorch and interfaced in R and would be made available at: https://github.com/lasandrall/RandMVLearn.

stat.ME↗

Deep IDA: A Deep Learning Method for Integrative Discriminant Analysis of Multi-View Data with Feature Ranking -- An Application to COVID-19 severity

COVID-19 severity is due to complications from SARS-Cov-2 but the clinical course of the infection varies for individuals, emphasizing the need to better understand the disease at the molecular level. We use clinical and multiple molecular data (or views) obtained from patients with and without COVID-19 who were (or not) admitted to the intensive care unit to shed light on COVID-19 severity. Methods for jointly associating the views and separating the COVID-19 groups (i.e., one-step methods) have focused on linear relationships. The relationships between the views and COVID-19 patient groups, however, are too complex to be understood solely by linear methods. Existing nonlinear one-step methods cannot be used to identify signatures to aid in our understanding of the complexity of the disease. We propose Deep IDA (Integrative Discriminant Analysis) to address analytical challenges in our problem of interest. Deep IDA learns nonlinear projections of two or more views that maximally associate the views and separate the classes in each view, and permits feature ranking for interpretable findings. Our applications demonstrate that Deep IDA has competitive classification rates compared to other state-of-the-art methods and is able to identify molecular signatures that facilitate an understanding of COVID-19 severity.

stat.ML↗

sJIVE: Supervised Joint and Individual Variation Explained

Analyzing multi-source data, which are multiple views of data on the same subjects, has become increasingly common in molecular biomedical research. Recent methods have sought to uncover underlying structure and relationships within and/or between the data sources, and other methods have sought to build a predictive model for an outcome using all sources. However, existing methods that do both are presently limited because they either (1) only consider data structure shared by all datasets while ignoring structures unique to each source, or (2) they extract underlying structures first without consideration to the outcome. We propose a method called supervised joint and individual variation explained (sJIVE) that can simultaneously (1) identify shared (joint) and source-specific (individual) underlying structure and (2) build a linear prediction model for an outcome using these structures. These two components are weighted to compromise between explaining variation in the multi-source data and in the outcome. Simulations show sJIVE to outperform existing methods when large amounts of noise are present in the multi-source data. An application to data from the COPDGene study reveals gene expression and proteomic patterns that are predictive of lung function. Functions to perform sJIVE are included in the R.JIVE package, available online at http://github.com/lockEF/r.jive .

stat.ML↗

Bayesian Integrative Analysis and Prediction with Application to Atherosclerosis Cardiovascular Disease

Cardiovascular diseases (CVD), including atherosclerosis CVD (ASCVD), are multifactorial diseases that present a major economic and social burden worldwide. Tremendous efforts have been made to understand traditional risk factors for ASCVD, but these risk factors account for only about half of all cases of ASCVD. It remains a critical need to identify nontraditional risk factors (e.g., genetic variants, genes) contributing to ASCVD. Further, incorporating functional knowledge in prediction models have the potential to reveal pathways associated with disease risk. We propose Bayesian hierarchical factor analysis models that associate multiple omics data, predict a clinical outcome, allow for prior functional information, and can accommodate clinical covariates. The models, motivated by available data and the need for other risk factors of ASCVD, are used for the integrative analysis of clinical, demographic, and multi-omics data to identify genetic variants, genes, and gene pathways potentially contributing to 10-year ASCVD risk in healthy adults. Our findings revealed several genetic variants, genes and gene pathways that were highly associated with ASCVD risk. Interestingly, some of these have been implicated in CVD risk. The others could be explored for their potential roles in CVD. Our findings underscore the merit in joint association and prediction models.

stat.ME↗

Sparse Linear Discriminant Analysis for Multi-view Structured Data

Classification methods that leverage the strengths of data from multiple sources (multi-view data) simultaneously have enormous potential to yield more powerful findings than two step methods: association followed by classification. We propose two methods, sparse integrative discriminant analysis (SIDA) and SIDA with incorporation of network information (SIDANet), for joint association and classification studies. The methods consider the overall association between multi-veiw data, and the separation within each view in choosing discriminant vectors that are associated and optimally separate subjects into different classes. SIDANet is among the first methods to incorporate prior structural information in joint association and classification studies. It uses the normalized Laplacian of a graph to smooth coefficients of predictor variables, thus encouraging selection of predictors that are connected and behave similarly. We demonstrate the effectiveness of our methods on a set of synthetic and real datasets. Our findings underscore the benefit of joint association and classification methods if the goal is to correlate multi-view data and to perform classification.

stat.ME↗

Multiple imputation using dimension reduction techniques for high-dimensional data

Missing data present challenges in data analysis. Naive analyses such as complete-case and available-case analysis may introduce bias and loss of efficiency, and produce unreliable results. Multiple imputation (MI) is one of the most widely used methods for handling missing data which can be partly attributed to its ease of use. However, existing MI methods implemented in most statistical software are not applicable to or do not perform well in high-dimensional settings where the number of predictors is large relative to the sample size. To remedy this issue, we develop an MI approach that uses dimension reduction techniques. Specifically, in constructing imputation models in the presence of high-dimensional data our approach uses sure independent screening followed by either sparse principal component analysis (sPCA) or sufficient dimension reduction (SDR) techniques. Our simulation studies, conducted for high-dimensional data, demonstrate that using SIS followed by sPCA to perform MI achieves better performance than the other imputation methods including several existing imputation approaches. We apply our approach to analysis of gene expression data from a prostate cancer study.

stat.ME↗

Sparse Generalized Eigenvalue Problem with Application to Canonical Correlation Analysis for Integrative Analysis of Methylation and Gene Expression Data

We present a method for individual and integrative analysis of high dimension, low sample size data that capitalizes on the recurring theme in multivariate analysis of projecting higher dimensional data onto a few meaningful directions that are solutions to a generalized eigenvalue problem. We propose a general framework, called SELP (Sparse Estimation with Linear Programming), with which one can obtain a sparse estimate for a solution vector of a generalized eigenvalue problem. We demonstrate the utility of SELP on canonical correlation analysis for an integrative analysis of methylation and gene expression profiles from a breast cancer study, and we identify some genes known to be associated with breast carcinogenesis, which indicates that the proposed method is capable of generating biologically meaningful insights. Simulation studies suggest that the proposed method performs competitive in comparison with some existing methods in identifying true signals in various underlying covariance structures.

stat.ME↗

Integrative analysis of transcriptomic and metabolomic data via sparse canonical correlation analysis with incorporation of biological information

Integrative analyses of different high dimensional data types are becoming increasingly popular. Similarly, incorporating prior functional relationships among variables in data analysis has been a topic of increasing interest as it helps elucidate underlying mechanisms among complex diseases. In this paper, the goal is to assess association between transcriptomic and metabolomic data from a Predictive Health Institute (PHI) study including healthy adults at high risk of developing cardiovascular diseases. To this end, we develop statistical methods for identifying sparse structure in canonical correlation analysis (CCA) with incorporation of biological/structural information. Our proposed methods use prior network structural information among genes and among metabolites to guide selection of relevant genes and metabolites in sparse CCA, providing insight on the molecular underpinning of cardiovascular disease. Our simulations demonstrate that the structured sparse CCA methods outperform several existing sparse CCA methods in selecting relevant genes and metabolites when structural information is informative and are robust to mis-specified structural information. Our analysis of the PHI study reveals that a number of genes and metabolic pathways including some known to be associated with cardiovascular diseases are enriched in the subset of genes and metabolites selected by our proposed approach.

stat.ME↗