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<p>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.</p>

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Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月5日

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

摘要

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.