Tissue schematics map the specialization of immune tissue motifs and their appropriation by tumors
Tissue schematics map the specialization of immune tissue motifs and their appropriation by tumors
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DOI：
10.1016/j.cels.2021.09.012
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发表时间：
2022-02-16
期刊：
影响因子：
9.3
通讯作者：
Nolan, Garry P.
中科院分区：
文献类型：
--
作者：
Bhate, Salil S.;Barlow, Graham L.;Nolan, Garry P.
生物系统的示意图，即其各个部分的表示、它们如何组合以及它们的作用，将有助于理解其基本组织以及发病机制或进化的改变。我们提出了一种从高参数成像数据构建组织示意图（TS）的计算方法以及解释它们的生物模型。 TS 将细胞邻域的空间组装映射到组织图案中，我们建议其模块化组合能够生成复杂的输出。我们在人类淋巴组织 (HLT) 中开发了我们的方法，将滤泡外区识别为相邻区域和核心淋巴组件之间的潜在中继，并具有每种 HLT 类型的修改特征。将 TS 方法应用于人类结直肠癌的肿瘤微环境，识别出一个高阶基序，其突变组装与患者生存呈负相关。因此，TS 可能会阐明免疫结构如何特化并变得容易受到肿瘤重新编程的影响。
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.