Accurate imputation of pathway-specific gene expression in spatial transcriptomics with PASTA

Date:	December 16, 2025
PMID:	PMC12820036
Category:	N/A
Authors:	Ruoxing Li, Peng Yang, Mauro Di Pilato, Jianjun Zhang, Christopher R Flowers, Lulu Shang 7, Ziyi Li
Abstract:

Mapping the entire transcriptome at single-cell resolution under its natural spatial context is essential for investigating the oncogenesis and progression of diseases. The recently emerged targeted in-situ technologies retain the spatial organization of cells at high resolution, although they remain limited in the number of genes that can be simultaneously measured. To overcome this obstacle, numerous computational methods have been developed to predict unmeasured gene expression in spatial transcriptomics data by leveraging scRNA-seq data. Most of these methods focus on the expression of individual genes and usually generate highly variable predictions. In this study, we introduce PASTA (PAthway-oriented Spatial gene impuTAtion), a spatial pathway expression imputation method that leverages cell type and spatial proximity to enhance prediction accuracy. PASTA assumes that nearby cells and cells of the same type exhibit similar expression patterns, along with pathway information integrated into the imputation process, which improves prediction robustness and enhances biological relevance in spatial transcriptomics data. We demonstrate PASTA's superior performance across both simulated and real-world datasets, highlighting its ability to impute pathway gene expression with improved stability and biological significance.

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Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.

The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:

Project Number:	Awardee Organization
U54CA274374	Fred Hutchinson Cancer Center
U54CA274375	Houston Methodist Research Institute
U54CA274370	Johns Hopkins University
U54CA274371	UT MD Anderson Cancer Center
U54CA274367	Vanderbilt University Medical Center