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Spatial isoform sequencing at single-cell resolution reveals cell-type-specific spatial isoform variability in multiple brain cell types

Nature Methods Bioinformatics AI Lieke Michielsen, Andrey D. Prjibelski, Careen Foord, Yelizaveta Spiegelman, Taewoo Kim, Wen Hu, Julien Jarroux, Justine Hsu, Rebecca Pfeil, Xinyi Zhang, Li Gan, Alexandru I. Tomescu, Iman Hajirasouliha, Hagen U. Tilgner 2026-09-04

TL;DR - This Nature Methods paper introduces Spl-ISO-Seq2, Spl-IsoQuant-2, and Spl-IsoFind for spatial isoform sequencing and analysis at single-cell resolution. Applied to mouse brain slices, the methods reveal cell-type-specific spatial variation in transcript isoforms.

Spl-ISO-Seq2 enables high-resolution spatial isoform sequencing.
Spl-IsoQuant-2 supports barcode calling at a scale exceeding 450 million barcodes.
Spl-IsoFind detects spatially variable isoforms across multiple brain cell types.
The workflow was demonstrated on mouse brain tissue slices.

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