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Recent technology breakthroughs in spatially resolved transcriptomics (SRT) have enabled the comprehensive molecular characterization of cells whilst preserving their spatial and gene expression contexts. One of the fundamental questions in analyzing SRT data is the identification of spatially variable genes whose expressions display spatially correlated patterns. Existing approaches are built upon either the Gaussian process-based model, which relies onad hockernels, or the energy-based Ising model, which requires gene expression to be measured on a lattice grid. To overcome these potential limitations, we developed a generalized energy-based framework to model gene expression measured from imaging-based SRT platforms, accommodating the irregular spatial distribution of measured cells. Our Bayesian model applies a zero-inflated negative binomial mixture model to dichotomize the raw count data, reducing noise. Additionally, we incorporate a geostatistical mark interaction model with a generalized energy function, where the interaction parameter is used to identify the spatial pattern. Auxiliary variable MCMC algorithms were employed to sample from the posterior distribution with an intractable normalizing constant. We demonstrated the strength of our method on both simulated and real data. Our simulation study showed that our method captured various spatial patterns with high accuracy; moreover, analysis of a seqFISH dataset and a STARmap dataset established that our proposed method is able to identify genes with novel and strong spatial patterns.
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A Bayesian modified Ising model for identifying spatially variable genes from spatial transcriptomics data
A recent technology breakthrough in spatial molecular profiling (SMP) has enabled the comprehensive molecular characterizations of single cells while preserving spatial information. It provides new opportunities to delineate how cells from different origins form tissues with distinctive structures and functions. One immediate question in SMP data analysis is to identify genes whose expressions exhibit spatially correlated patterns, called spatially variable (SV) genes. Most current methods to identify SV genes are built upon the geostatistical model with Gaussian process to capture the spatial patterns. However, the Gaussian process models rely on ad hoc kernels that could limit the models' ability to identify complex spatial patterns. In order to overcome this challenge and capture more types of spatial patterns, we introduce a Bayesian approach to identify SV genes via a modified Ising model. The key idea is to use the energy interaction parameter of the Ising model to characterize spatial expression patterns. We use auxiliary variable Markov chain Monte Carlo algorithms to sample from the posterior distribution with an intractable normalizing constant in the model. Simulation studies using both simulated and synthetic data showed that the energy‐based modeling approach led to higher accuracy in detecting SV genes than those kernel‐based methods. When applied to two real spatial transcriptomics (ST) datasets, the proposed method discovered novel spatial patterns that shed light on the biological mechanisms. In summary, the proposed method presents a new perspective for analyzing ST data.
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- Award ID(s):
- 2210912
- PAR ID:
- 10444450
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Statistics in Medicine
- Volume:
- 41
- Issue:
- 23
- ISSN:
- 0277-6715
- Format(s):
- Medium: X Size: p. 4647-4665
- Size(s):
- p. 4647-4665
- Sponsoring Org:
- National Science Foundation
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