Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University Schools of Medicine and Engineering, Stanford University, Stanford, CA 94305, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
Cell Syst. 2022 Feb 16;13(2):109-130.e6. doi: 10.1016/j.cels.2021.09.012. Epub 2021 Oct 14.
A schematic of a biological system, i.e., a representation of its pieces, how they are combined, and what they do, would facilitate understanding its essential organization and alteration in pathogenesis or evolution. We present a computational approach for constructing tissue schematics (TSs) from high-parameter imaging data and a biological model for interpreting them. TSs map the spatial assembly of cellular neighborhoods into tissue motifs, whose modular composition, we propose, enables the generation of complex outputs. We developed our approach in human lymphoid tissue (HLT), identifying the follicular outer zone as a potential relay between neighboring zones and a core lymphoid assembly with modifications characteristic of each HLT type. Applying the TS approach to the tumor microenvironment in human colorectal cancer identified a higher-order motif, whose mutated assembly was negatively associated with patient survival. TSs may therefore elucidate how immune architectures can be specialized and become vulnerable to reprogramming by tumors.
生物系统的示意图，即其组成部分、它们如何组合以及它们的功能的表示形式，将有助于理解其在发病机制或进化过程中的基本组织和改变。我们提出了一种从高参数成像数据构建组织示意图（TS）的计算方法和一种用于解释它们的生物学模型。TS 将细胞邻域的空间组装映射到组织模式中，我们提出，其模块化组成能够产生复杂的输出。我们在人类淋巴组织（HLT）中开发了我们的方法，确定滤泡外区作为相邻区之间的潜在中继，以及具有每个 HLT 类型特征的修改的核心淋巴组装。将 TS 方法应用于人类结直肠癌的肿瘤微环境中，确定了一个更高阶的模式，其突变的组装与患者的生存呈负相关。因此，TS 可以阐明免疫结构如何专门化并变得容易受到肿瘤的重新编程。
