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SC-MEB: spatial clustering with hidden Markov random field using empirical Bayes.

ABSTRACT: Spatial transcriptomics has been emerging as a powerful technique for resolving gene expression profiles while retaining tissue spatial information. These spatially resolved transcriptomics make it feasible to examine the complex multicellular systems of different microenvironments. To answer scientific questions with spatial transcriptomics and expand our understanding of how cell types and states are regulated by microenvironment, the first step is to identify cell clusters by integrating the available spatial information. Here, we introduce SC-MEB, an empirical Bayes approach for spatial clustering analysis using a hidden Markov random field. We have also derived an efficient expectation-maximization algorithm based on an iterative conditional mode for SC-MEB. In contrast to BayesSpace, a recently developed method, SC-MEB is not only computationally efficient and scalable to large sample sizes but is also capable of choosing the smoothness parameter and the number of clusters. We performed comprehensive simulation studies to demonstrate the superiority of SC-MEB over some existing methods. We applied SC-MEB to analyze the spatial transcriptome of human dorsolateral prefrontal cortex tissues and mouse hypothalamic preoptic region. Our analysis results showed that SC-MEB can achieve a similar or better clustering performance to BayesSpace, which uses the true number of clusters and a fixed smoothness parameter. Moreover, SC-MEB is scalable to large 'sample sizes'. We then employed SC-MEB to analyze a colon dataset from a patient with colorectal cancer (CRC) and COVID-19, and further performed differential expression analysis to identify signature genes related to the clustering results. The heatmap of identified signature genes showed that the clusters identified using SC-MEB were more separable than those obtained with BayesSpace. Using pathway analysis, we identified three immune-related clusters, and in a further comparison, found the mean expression of COVID-19 signature genes was greater in immune than non-immune regions of colon tissue. SC-MEB provides a valuable computational tool for investigating the structural organizations of tissues from spatial transcriptomic data.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8690176 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Air pollution is a matter of concern among the public, especially for those living in urban and industrial areas. Markov chain modeling is often used to model the underlying dynamics of air pollution, which involves describing the transition probability of going from one air pollution state to another. Thus, estimating the transition probability matrix for the data of the air pollution index (API) is an essential process in the modeling. However, one may observe many zero probabilities in the transition probability matrix, especially when faced with a small sample, interpreting the results with respect to the climate condition less realistic. This study proposes a robust empirical Bayes method, which incorporates a method of smoothing the zero frequencies in the count matrix, contributing to an improved estimation of the transition probability matrix. The robustness of the empirical Bayesian estimation is investigated based on Bayes risk. The transition probability matrices estimated based on the robust empirical Bayes method for the hourly API data collected from seven monitoring stations in Malaysia for the period 2012 to 2014 are used for determining the air pollution characteristics such as the mean residence time, the steady-state probability and the mean recurrence time. Furthermore, the proposed method has been evaluated by Monte Carlo simulations. Results suggest that it is quite effective in producing non-zero transition probability estimates, and superior to the maximum likelihood method in terms of minimizing the mean squared error for individual and entire transition probabilities. Therefore, the robust empirical Bayes method proves to be an improved approach to the estimation of the Markov chain. When applied to API data, it could provide important information on air pollution dynamics that may help guiding the development of proper strategies for managing the impact of air quality.Supplementary informationThe online version contains supplementary material available at 10.1007/s40201-020-00607-4.

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SC-MEB: spatial clustering with hidden Markov random field using empirical Bayes.

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