Spatial multiomics in biomedical research: advances beyond transcriptomics
Xinchen Mao, Zhuo Chen, Emily J. Hwang, Jun Liu, Junrou Huang, Haikuo Li
Xinchen Mao, Zhuo Chen, Emily J. Hwang, Jun Liu, Junrou Huang, Haikuo Li
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Review

Spatial multiomics in biomedical research: advances beyond transcriptomics

Abstract

Coordinated changes in gene expression, epigenetic regulation, protein and metabolic activities together drive disease progression and determine clinical outcomes. While spatially resolved transcriptomics has been widely adopted across biomedical fields, it offers an incomplete picture limited to transcriptomic levels. Here, we survey the latest developments in spatial multiomics technologies, with particular emphasis on platforms that extend beyond conventional transcriptomics and profile genomics, epigenomics, proteomics, or metabolomics within intact tissues. These approaches are rapidly becoming commercialized, and here we highlight major technical breakthroughs, enhanced sample compatibility, emerging applications, and computational tools for data analysis. This Review aims to equip researchers with a clear understanding of the current technological landscape and to accelerate the adoption of spatial multiomics methods in biomedical research.

Authors

Xinchen Mao, Zhuo Chen, Emily J. Hwang, Jun Liu, Junrou Huang, Haikuo Li

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Figure 1

Representative spatial omics technologies for non-transcriptome modalities and their simplified workflows.

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Representative spatial omics technologies for non-transcriptome modaliti...
Deterministic barcoding in tissue sequencing (DBiT-seq) (9): Co-profiling of protein Ab-derived tags and transcripts on a microfluidic platform. Spatially resolved profiling of histone modifications using in situ cleavage under targets and tagmentation (spatial-CUT&Tag) (14) and spatially resolved assay for transposase-accessible chromatin using sequencing (spatial-ATAC-seq) (13): Analysis of chromatin-associated protein binding and chromatin accessibility profiles with the DBiT-seq microfluidic platform. The illustration presents spatial-CUT&Tag-RNA-seq and spatial-ATAC-RNA-seq (58, 60), which enable simultaneous profiling of the epigenome and transcriptome. Slide-DNA-seq (40): Spatially resolved genome sequencing using microbead arrays with unique DNA barcodes. Perturb-map (46): Spatial functional genomics based on CRISPR/Cas9 gene modification. MALDI mass spectrometry imaging (MALDI-MSI) (21): MS-based spatial metabolomics technology achieved through spot laser irradiation. PDMS, polydimethylsiloxane; RT, reverse transcription; NGS, next-generation sequencing.