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Alvin Sheng

Publications and source records attributed to Alvin Sheng.

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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

A Two-Stage Approach for Segmenting Spatial Point Patterns Applied to Multiplex Imaging

Recent advances in multiplex imaging have enabled researchers to locate different types of cells within a tissue sample. This is especially relevant for tumor immunology, as clinical regimes corresponding to different stages of disease or responses to treatment may manifest as different spatial arrangements of tumor and immune cells. Spatial point pattern modeling can be used to partition multiplex tissue images according to these regimes. To this end, we propose a two-stage approach: first, local intensities and pair correlation functions are estimated from the spatial point pattern of cells within each image, and the pair correlation functions are reduced in dimension via spectral decomposition of the covariance function. Second, the estimates are clustered in a Bayesian hierarchical model with spatially-dependent cluster labels. The clusters correspond to regimes of interest that are present across subjects; the cluster labels segment the spatial point patterns according to those regimes. Through Markov Chain Monte Carlo sampling, we jointly estimate and quantify uncertainty in the cluster assignment and spatial characteristics of each cluster. Simulations demonstrate the performance of the method, and it is applied to a set of multiplex immunofluorescence images of diseased pancreatic tissue.

stat.ME