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SpaGCN: Integrating gene expression, spatial location and histology to identify spatial domains and spatially variable genes by graph convolutional network

Abstract

Recent advances in spatially resolved transcriptomics (SRT) technologies have enabled comprehensive characterization of gene expression patterns in the context of tissue microenvironment. To elucidate spatial gene expression variation, we present SpaGCN, a graph convolutional network approach that integrates gene expression, spatial location and histology in SRT data analysis. Through graph convolution, SpaGCN aggregates gene expression of each spot from its neighboring spots, which enables the identification of spatial domains with coherent expression and histology. The subsequent domain guided differential expression (DE) analysis then detects genes with enriched expression patterns in the identified domains. Analyzing seven SRT datasets using SpaGCN, we show it can detect genes with much more enriched spatial expression patterns than competing methods. Furthermore, genes detected by SpaGCN are transferrable and can be utilized to study spatial variation of gene expression in other datasets. SpaGCN is computationally fast, platform independent, making it a desirable tool for diverse SRT studies.

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Fig. 1: Workflow of SpaGCN.
Fig. 2: Spatial domains and SVGs detected in the human primary pancreatic cancer tissue data.
Fig. 3: Spatial domains and SVGs detected in the LIBD human dorsolateral prefrontal cortex data.
Fig. 4: Spatial domains and SVGs detected in the mouse brain posterior brain data.
Fig. 5: Joint spatial domain detection across multiple mouse brain tissue sections using SpaGCN.
Fig. 6: Spatial domains and SVGs detected in the mouse visual cortex STARmap data.

Data availability

The authors analyzed seven publicly available SRT datasets. The data were acquired from the following websites or accession numbers: (1) human primary pancreatic cancer ST data (GSE111672); (2) LIBD human dorsolateral prefrontal cortex, dorsolateral prefrontal cortex 10x Visium data (http://research.libd.org/spatialLIBD/); (3) mouse posterior brain 10x Visium data (https://support.10xgenomics.com/spatial-gene-expression/datasets/1.0.0/V1_Mouse_Brain_Sagittal_Posterior); (4) mouse cortex SLIDE-seqV2 data (https://singlecell.broadinstitute.org/single_cell/study/SCP815/highly-sensitive-spatial-transcriptomics-at-near-cellular-resolution-with-slide-seqv2); (5) mouse visual cortex STARmap data (https://www.starmapresources.com/data); (6) mouse olfactory bulb ST data (https://drive.google.com/drive/folders/1C4l3lBaYl7uuV2AA2o0WDzO_mkc_b0pv?usp=sharing); (7) mouse hypothalamus MERFISH data (https://datadryad.org/stash/dataset/doi:10.5061/dryad.8t8s248). Details of the datasets analyzed in this paper are described in Supplementary Table 1.

Code availability

An open-source implementation of the SpaGCN algorithm can be downloaded from https://github.com/jianhuupenn/SpaGCN.

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Acknowledgements

This work was supported by the following grants: R01GM125301, R01EY030192, R01EY031209, R01HL113147 and R01HL150359 (to M.L.), and P01AG066597 (to D.J.I. and E.B.L.). We thank R. Moncada and I. Yanai for sharing the human pancreatic cancer histology image data, and R. Stickles, E. Murray, E. Macosko and F. Chen for sharing the SLIDE-seqV2 data.

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Authors

Contributions

This study was conceived of and led by M.L. J.H. designed the model and algorithm. J.H. implemented the SpaGCN software and led the data analysis with input from M.L., X.L., K.C., A.S., N.M., D.I., E.L. and R.T.S. N.M. contributed to figure design and generation. J.H. and M.L. wrote the paper with feedback from all other coauthors.

Corresponding authors

Correspondence to Jian Hu or Mingyao Li.

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The authors declare no competing interests.

Additional information

Peer review information Nature Methods thanks Andrew Jaffe, Kristen Maynard and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Lin Tang was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Supplementary information

Supplementary Information

Supplementary Tables 1–3, Figs. 1–42 and Notes 1–3.

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Hu, J., Li, X., Coleman, K. et al. SpaGCN: Integrating gene expression, spatial location and histology to identify spatial domains and spatially variable genes by graph convolutional network. Nat Methods 18, 1342–1351 (2021). https://doi.org/10.1038/s41592-021-01255-8

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