哥伦比亚大学Raul Rabadan小组的一项最新研究利用SPLISOSM从空间转录组学数据中绘制同种异构体和调控机制。2026年1月5日出版的《自然—生物技术》发表了这项成果。

在这里，研究团队提出SPLISOSM（空间异构体统计建模），一种从空间转录组学数据中检测异构体分辨率模式的方法。SPLISOSM使用非参数内核进行多变量测试，以考虑点级和同形级依赖关系，在稀疏数据上实现高统计能力。在单主题脑中，研究团队确定了超过1000个空间可变的转录多样性事件，主要是在与神经精神疾病相关的突触信号通路中，并揭示了已知和以前未知的与区域特异性RNA结合蛋白的调节关系。课题组研究人员进一步表明，这些模式在小鼠和人类前额皮质之间是进化保守的。人类胶质母细胞瘤的分析强调了与特定微环境条件相关的抗原呈递和粘附基因的普遍转录多样性。总之，该课题组人员提出了一个全面的空间剪接分析在正常和肿瘤条件下的大脑。

据介绍，转录物多样性包括剪接和选择性3'端图像对细胞身份和适应性至关重要，但其空间协调性尚不清楚。

附：英文原文

Title: Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM

Author: Su, Jiayu, Qu, Yiming, Schertzer, Megan, Yang, Haochen, Jiang, Jiahao, Lhakhang, Tenzin, Nelson, Theodore M., Park, Stella, Lai, Qiliang, Fu, Xi, Choi, Seung-won, Knowles, David A., Rabadan, Raul

Issue&Volume: 2026-01-05

Abstract: Transcript diversity including splicing and alternative 3′ end usage is crucial for cellular identity and adaptation, yet its spatial coordination remains poorly understood. Here we present SPLISOSM (spatial isoform statistical modeling), a method for detecting isoform-resolution patterns from spatial transcriptomics data. SPLISOSM uses multivariate testing with nonparametric kernels to account for spot-level and isoform-level dependencies, achieving high statistical power on sparse data. In the mouse brain, we identify over 1,000 spatially variable transcript diversity events, primarily in synaptic signaling pathways linked to neuropsychiatric disorders, and uncover both known and previously unknown regulatory relationships with region-specific RNA binding proteins. We further show that these patterns are evolutionarily conserved between mouse and human prefrontal cortex. Analysis of human glioblastoma highlights pervasive transcript diversity in antigen presentation and adhesion genes associated with specific microenvironmental conditions. Together, we present a comprehensive spatial splicing analysis in the brain under normal and neoplastic conditions.

DOI: 10.1038/s41587-025-02965-6

Source: https://www.nature.com/articles/s41587-025-02965-6