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Updated: Jan 13, 2026

Mining Spatial Transcriptomics Datasets using DeepSpaceDB
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Mapping isoforms and regulatory mechanisms from spatial transcriptomics data with SPLISOSM.

Jiayu Su1,2,3, Yiming Qu4, Megan Schertzer5

  • 1Program for Mathematical Genomics, Columbia University, New York, NY, USA. js5756@cumc.columbia.edu.

Nature Biotechnology
|January 6, 2026
PubMed
Summary
This summary is machine-generated.

We developed SPLISOSM to map transcript diversity in spatial transcriptomics data. This method reveals thousands of spatially variable splicing events in the brain, linked to neuropsychiatric disorders and cancer.

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Area of Science:

  • Genomics
  • Neuroscience
  • Computational Biology

Background:

  • Transcript diversity, including splicing and alternative 3' end usage, is vital for cellular function but its spatial regulation is unclear.
  • Spatial transcriptomics offers a way to study gene expression in its tissue context.

Purpose of the Study:

  • To develop a method for detecting isoform-resolution patterns in spatial transcriptomics data.
  • To analyze spatial transcript diversity in the mouse and human brain under normal and neoplastic conditions.

Main Methods:

  • Introduced SPLISOSM (spatial isoform statistical modeling), a method using multivariate testing with nonparametric kernels.
  • Applied SPLISOSM to spatial transcriptomics data from mouse and human brain samples, including glioblastoma.

Main Results:

  • Identified over 1,000 spatially variable transcript diversity events in the mouse brain, enriched in synaptic signaling pathways related to neuropsychiatric disorders.
  • Uncovered conserved spatial splicing patterns between mouse and human prefrontal cortex.
  • Revealed pervasive transcript diversity in human glioblastoma, associated with antigen presentation and adhesion genes and specific microenvironments.

Conclusions:

  • SPLISOSM enables powerful statistical analysis of spatial transcript diversity even with sparse data.
  • Spatial transcript diversity plays a significant role in brain function, neuropsychiatric disorders, and cancer.
  • This study provides a comprehensive spatial splicing analysis of the brain in health and disease.