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一种具有特征选择的可解释贝叶斯聚类方法,用于分析空间分辨转录组学数据。

An interpretable Bayesian clustering approach with feature selection for analyzing spatially resolved transcriptomics data.

机构信息

Department of Mathematical Sciences, The University of Texas at Dallas, Richardson, TX 75080, United States.

Department of Statistics, The Chinese University of Hong Kong, Hong Kong SAR, China.

出版信息

Biometrics. 2024 Jul 1;80(3). doi: 10.1093/biomtc/ujae066.

Abstract

Recent breakthroughs in spatially resolved transcriptomics (SRT) technologies have enabled comprehensive molecular characterization at the spot or cellular level while preserving spatial information. Cells are the fundamental building blocks of tissues, organized into distinct yet connected components. Although many non-spatial and spatial clustering approaches have been used to partition the entire region into mutually exclusive spatial domains based on the SRT high-dimensional molecular profile, most require an ad hoc selection of less interpretable dimensional-reduction techniques. To overcome this challenge, we propose a zero-inflated negative binomial mixture model to cluster spots or cells based on their molecular profiles. To increase interpretability, we employ a feature selection mechanism to provide a low-dimensional summary of the SRT molecular profile in terms of discriminating genes that shed light on the clustering result. We further incorporate the SRT geospatial profile via a Markov random field prior. We demonstrate how this joint modeling strategy improves clustering accuracy, compared with alternative state-of-the-art approaches, through simulation studies and 3 real data applications.

摘要

近年来,基于空间分辨转录组学(SRT)技术的突破,使得在保留空间信息的同时,能够在点或细胞水平上进行全面的分子特征描述。细胞是组织的基本组成部分,组织成不同但又相互连接的成分。虽然已经有许多非空间和空间聚类方法被用于根据 SRT 高维分子谱将整个区域划分为相互排斥的空间域,但大多数方法都需要专门选择不太可解释的降维技术。为了克服这一挑战,我们提出了一种零膨胀负二项混合模型,以根据分子谱对斑点或细胞进行聚类。为了提高可解释性,我们采用特征选择机制,根据区分基因提供 SRT 分子谱的低维摘要,从而揭示聚类结果。我们进一步通过马尔可夫随机场先验来整合 SRT 地理空间谱。通过模拟研究和 3 个真实数据应用,我们展示了这种联合建模策略如何提高聚类准确性,与替代的最先进方法相比。

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