Recent technology breakthroughs in spatial molecular profiling (SMP), such as spatial transcriptomics sequencing, have enabled the comprehensive molecular characterization of single cells while preserving spatial and morphological information. One immediate question is how to identify spatially variable (SV) genes. Most of the current work builds upon the geostatistical model with Gaussian process that relies on the selection of \textit{ad hoc} kernels to account for spatial expression patterns. To overcome this potential challenge and capture more spatial patterns, we introduced a Bayesian modeling framework to identify SV genes. Our model first dichotomized the complex sequencing count data into latent binary gene expression levels. Then, binary pattern quantification problem is considered as a spatial correlation estimation problem via a modified Ising model using Hamiltonian energy to characterize spatial patterns. We used auxiliary variable Markov chain Monte Carlo algorithms to sample from the posterior distribution with an intractable normalizing constant. Simulation results showed high accuracy in detecting SV genes compared with kernel-based alternatives. We also applied our model to two real datasets and discovered novel spatial patterns that shed light on the biological mechanisms. This statistical methodology presents a new perspective for characterizing spatial patterns from SMP data.
翻译:空间分子剖析(SMP)方面最近的技术突破,如空间转录缩记式测序等,使得在保留空间和形态信息的同时,能够对单细胞进行全面的分子定性,同时保留空间和形态信息。一个直接的问题是如何确定空间变数(SV)基因。目前大部分工作以Gausian过程的地理统计模型为基础,而Gausian过程依赖于选择空间表达模式。为了克服这一潜在挑战并捕捉更多的空间模式,我们引入了巴伊西亚模型框架,以识别SV基因。我们的模型首先将复杂的测序计算数据分解成潜伏的二进制基因表达水平。然后,二进制模式量化问题被视为一个空间相关估计问题,通过一个使用汉密尔顿能源来描述空间模式的修改的Ising模型。我们用辅助变量Markov链 Monte Carlo 算法样本从远端分布中采集,并有一个难调和的正常的常态。模拟结果显示,与基于内核的替代方法相比,SV基因的探测高度精确性。我们还将我们的模型应用于两个真实的模型,并发现了从生物光基空间模式的Smmmmmmmmm和新空间模型,以显示新的空间模型显示新的空间模式。