category
bioRxiv
date
Feb 25, 2026
slug
status
Published
summary
提出STRATA方法,通过微分几何框架构建连续调控子活动场,量化转录因子程序间的局部共调控关系,并发现黑色素瘤微环境通过降低调控子耦合方差和相界强度实现组织均质化。
tags
空间组学
type
Post

📄 原文题目

STRATA: Spatial Regulon Field Theory Reveals Coupling Architecture of Human Skin and Its Homogenization in Melanoma

🔗 原文链接

💡 AI 核心解读

提出STRATA方法,通过微分几何框架构建连续调控子活动场,量化转录因子程序间的局部共调控关系,并发现黑色素瘤微环境通过降低调控子耦合方差和相界强度实现组织均质化。

📝 英文原版摘要

Spatial transcriptomics captures gene expression in tissue context, yet current analyses reduce continuous regulatory landscapes to discrete cell clusters, discarding the geometry of intercellular regulation. Here we introduce STRATA (Spatial Transcription-factor Regulatory Architecture of Tissue Analysis), a differential-geometric framework that constructs continuous regulon activity fields from transcript coordinates, computes their coupling tensor to quantify local co-regulation between transcription factor programs, and derives a Regulon Stability Index from the Jacobian singular value decomposition. Applied to Xenium in situ data from human skin melanoma (382 genes, 13.7 million transcripts), STRATA identifies coupling phase boundaries -- positions where the regulatory logic of tissue changes -- that track histological tissue architecture (Pearson r = 0.32 with the dermal-epidermal junction marker KRT-diff, r = 0.51 with maximum principal stretch; P < 10^-10). Within-tissue comparison reveals that the melanoma microenvironment does not abolish regulon coupling but homogenizes it: coupling variance decreases 28% and phase boundary intensity drops 18% relative to the epidermal zone. STRATA transforms spatial transcriptomics from cell cataloguing to continuous field analysis of regulatory tissue architecture.
酵母rDNA作为rDNAmine重复分析流程的基准基因工程猪模型的单核转录组学揭示小胶质细胞与T细胞相互作用驱动亨廷顿病神经退行性变
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