通过空间转录组分析,用细胞微环境特征精准区分炎症性肠病亚型。
Engineering Spatial and Molecular Features from Cellular Niches to Inform Predictions of Inflammatory Bowel Disease
- 基于非负矩阵分解识别出4类功能微环境。
- 构建44个特征,三分类准确率达77.4%、二分类达91.6%。
- 揭示空间结构紊乱是炎症关键信号,基因表达差异区分亚型。
区分炎症性肠病(IBD)的两种主要亚型——克罗恩病(CD)和溃疡性结肠炎(UC)是临床长期挑战,因症状重叠。本研究提出一种新型计算框架,利用空间转录组(ST)数据建立可解释的机器学习模型用于IBD分类。分析了健康对照(HC)、UC和CD患者结肠黏膜的ST数据。通过非负矩阵分解(NMF)识别出4个重复出现的细胞微环境,代表组织内不同的功能微环境。从这些微环境中系统构建了44个特征,涵盖微环境组成、邻近富集和微环境-基因信号三个病理维度。基于这些特征训练的多层感知机(MLP)分类器在更难的三分类任务(HC、UC、CD)中达到0.774 ± 0.161的准确率,在区分IBD与健康组织的二分类任务中达到0.916 ± 0.118。关键的是,模型可解释性分析显示,微环境的空间组织紊乱是炎症总体预测最强信号,而UC与CD的区分则依赖于特定微环境-基因表达谱。该工作提供了一个稳健的验证性流程,将描述性空间数据转化为精准且可解释的预测工具,不仅有望催生新诊断范式,还深化了对驱动不同IBD亚型生物学机制的理解。
原文摘要 · Abstract (English)
Differentiating between the two main subtypes of Inflammatory Bowel Disease (IBD): Crohns disease (CD) and ulcerative colitis (UC) is a persistent clinical challenge due to overlapping presentations. This study introduces a novel computational framework that employs spatial transcriptomics (ST) to create an explainable machine learning model for IBD classification. We analyzed ST data from the colonic mucosa of healthy controls (HC), UC, and CD patients. Using Non-negative Matrix Factorization (NMF), we first identified four recurring cellular niches, representing distinct functional microenvironments within the tissue. From these niches, we systematically engineered 44 features capturing three key aspects of tissue pathology: niche composition, neighborhood enrichment, and niche-gene signals. A multilayer perceptron (MLP) classifier trained on these features achieved an accuracy of $0.774 \pm 0.161$ for the more challenging three-class problem (HC, UC, and CD) and $0.916 \pm 0.118$ in the two-class problem of distinguishing IBD from healthy tissue. Crucially, model explainability analysis revealed that disruptions in the spatial organization of niches were the strongest predictors of general inflammation, while the classification between UC and CD relied on specific niche-gene expression signatures. This work provides a robust, proof-of-concept pipeline that transforms descriptive spatial data into an accurate and explainable predictive tool, offering not only a potential new diagnostic paradigm but also deeper insights into the distinct biological mechanisms that drive IBD subtypes.
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