Lee Kyu Ha, Coull Brent A, Majumder Suman, Riviere Patrick J La, Welch Jessica L Mark, Starr Jacqueline R
ArXiv. 2025 Feb 14:arXiv:2502.10513v1.
Advances in cellular imaging technologies, especially those based on fluorescence in situ hybridization (FISH) now allow detailed visualization of the spatial organization of human or bacterial cells. Quantifying this spatial organization is crucial for understanding the function of multicellular tissues or biofilms, with implications for human health and disease. To address the need for better methods to achieve such quantification, we propose a flexible multivariate point process model that characterizes and estimates complex spatial interactions among multiple cell types. The proposed Bayesian framework is appealing due to its unified estimation process and the ability to directly quantify uncertainty in key estimates of interest, such as those of inter-type correlation and the proportion of variance due to inter-type relationships. To ensure stable and interpretable estimation, we consider shrinkage priors for coefficients associated with latent processes. Model selection and comparison are conducted by using a deviance information criterion designed for models with latent variables, effectively balancing the risk of overfitting with that of oversimplifying key quantities. Furthermore, we develop a hierarchical modeling approach to integrate multiple image-specific estimates from a given subject, allowing inference at both the global and subject-specific levels. We apply the proposed method to microbial biofilm image data from the human tongue dorsum and find that specific taxon pairs, such as Streptococcus mitis-Streptococcus salivarius and Streptococcus mitis-Veillonella, exhibit strong positive spatial correlations, while others, such as Actinomyces-Rothia, show slight negative correlations. For most of the taxa, a substantial portion of spatial variance can be attributed to inter-taxon relationships.
细胞成像技术的进步,尤其是基于荧光原位杂交(FISH)的技术,现在能够详细观察人类或细菌细胞的空间组织。量化这种空间组织对于理解多细胞组织或生物膜的功能至关重要,这对人类健康和疾病具有重要意义。为了满足对更好方法进行此类量化的需求,我们提出了一种灵活的多元点过程模型,该模型可以表征和估计多种细胞类型之间复杂的空间相互作用。所提出的贝叶斯框架很有吸引力,因为它具有统一的估计过程,并且能够直接量化关键估计值中的不确定性,例如类型间相关性以及由于类型间关系导致的方差比例。为了确保稳定且可解释的估计,我们考虑对与潜在过程相关的系数采用收缩先验。通过使用为具有潜在变量的模型设计的偏差信息准则进行模型选择和比较,有效地平衡了过度拟合风险与过度简化关键量的风险。此外,我们开发了一种层次建模方法,以整合来自给定受试者的多个特定图像估计值,从而在全局和受试者特定水平上进行推断。我们将所提出的方法应用于来自人类舌背的微生物生物膜图像数据,发现特定的分类群对,如缓症链球菌 - 唾液链球菌和缓症链球菌 - 韦荣球菌,呈现出强烈的正空间相关性,而其他分类群对,如放线菌 - 罗氏菌,则呈现出轻微的负相关性。对于大多数分类群而言,相当一部分空间方差可归因于分类群间的关系。