SpatialDM for Rapid Identification of Spatially Co-expressed Ligand-receptor and Revealing Cell-cell Communication Patterns

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jul 6

PMID 37414760

Authors

Zhuoxuan Li

Tianjie Wang

Pentao Liu

Yuanhua Huang

Affiliations

Soon will be listed here.

Abstract

Cell-cell communication is a key aspect of dissecting the complex cellular microenvironment. Existing single-cell and spatial transcriptomics-based methods primarily focus on identifying cell-type pairs for a specific interaction, while less attention has been paid to the prioritisation of interaction features or the identification of interaction spots in the spatial context. Here, we introduce SpatialDM, a statistical model and toolbox leveraging a bivariant Moran's statistic to detect spatially co-expressed ligand and receptor pairs, their local interacting spots (single-spot resolution), and communication patterns. By deriving an analytical null distribution, this method is scalable to millions of spots and shows accurate and robust performance in various simulations. On multiple datasets including melanoma, Ventricular-Subventricular Zone, and intestine, SpatialDM reveals promising communication patterns and identifies differential interactions between conditions, hence enabling the discovery of context-specific cell cooperation and signalling.

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References

Madsen-Bouterse S, Romero R, Tarca A, Kusanovic J, Espinoza J, Kim C . The transcriptome of the fetal inflammatory response syndrome. Am J Reprod Immunol. 2010; 63(1):73-92. PMC: 3437779. DOI: 10.1111/j.1600-0897.2009.00791.x. View

Longo S, Guo M, Ji A, Khavari P . Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics. Nat Rev Genet. 2021; 22(10):627-644. PMC: 9888017. DOI: 10.1038/s41576-021-00370-8. View

Tyler S, Rotti P, Sun X, Yi Y, Xie W, Winter M . PyMINEr Finds Gene and Autocrine-Paracrine Networks from Human Islet scRNA-Seq. Cell Rep. 2019; 26(7):1951-1964.e8. PMC: 6394844. DOI: 10.1016/j.celrep.2019.01.063. View

Romero R, Gomez R, Ghezzi F, Yoon B, Mazor M, Edwin S . A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol. 1998; 179(1):186-93. DOI: 10.1016/s0002-9378(98)70271-6. View

Bloemendal S, Kuck U . Cell-to-cell communication in plants, animals, and fungi: a comparative review. Naturwissenschaften. 2012; 100(1):3-19. DOI: 10.1007/s00114-012-0988-z. View

Shao X, Li C, Yang H, Lu X, Liao J, Qian J . Knowledge-graph-based cell-cell communication inference for spatially resolved transcriptomic data with SpaTalk. Nat Commun. 2022; 13(1):4429. PMC: 9338929. DOI: 10.1038/s41467-022-32111-8. View

Thrane K, Eriksson H, Maaskola J, Hansson J, Lundeberg J . Spatially Resolved Transcriptomics Enables Dissection of Genetic Heterogeneity in Stage III Cutaneous Malignant Melanoma. Cancer Res. 2018; 78(20):5970-5979. DOI: 10.1158/0008-5472.CAN-18-0747. View

Armingol E, Officer A, Harismendy O, Lewis N . Deciphering cell-cell interactions and communication from gene expression. Nat Rev Genet. 2020; 22(2):71-88. PMC: 7649713. DOI: 10.1038/s41576-020-00292-x. View

Dries R, Zhu Q, Dong R, Eng C, Li H, Liu K . Giotto: a toolbox for integrative analysis and visualization of spatial expression data. Genome Biol. 2021; 22(1):78. PMC: 7938609. DOI: 10.1186/s13059-021-02286-2. View

10.

Bernstein M, Ni Z, Prasad A, Brown J, Mohanty C, Stewart R . SpatialCorr identifies gene sets with spatially varying correlation structure. Cell Rep Methods. 2023; 2(12):100369. PMC: 9795364. DOI: 10.1016/j.crmeth.2022.100369. View

11.

Tirosh I, Izar B, Prakadan S, Wadsworth 2nd M, Treacy D, Trombetta J . Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016; 352(6282):189-96. PMC: 4944528. DOI: 10.1126/science.aad0501. View

12.

Eng C, Lawson M, Zhu Q, Dries R, Koulena N, Takei Y . Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature. 2019; 568(7751):235-239. PMC: 6544023. DOI: 10.1038/s41586-019-1049-y. View

13.

Kelleher M, Singh R, ODriscoll C, Melgar S . Carcinoembryonic antigen (CEACAM) family members and Inflammatory Bowel Disease. Cytokine Growth Factor Rev. 2019; 47:21-31. DOI: 10.1016/j.cytogfr.2019.05.008. View

14.

Liu Y, Yang M, Deng Y, Su G, Enninful A, Guo C . High-Spatial-Resolution Multi-Omics Sequencing via Deterministic Barcoding in Tissue. Cell. 2020; 183(6):1665-1681.e18. PMC: 7736559. DOI: 10.1016/j.cell.2020.10.026. View

15.

Almet A, Cang Z, Jin S, Nie Q . The landscape of cell-cell communication through single-cell transcriptomics. Curr Opin Syst Biol. 2021; 26:12-23. PMC: 8104132. DOI: 10.1016/j.coisb.2021.03.007. View

16.

Vento-Tormo R, Efremova M, Botting R, Turco M, Vento-Tormo M, Meyer K . Single-cell reconstruction of the early maternal-fetal interface in humans. Nature. 2018; 563(7731):347-353. PMC: 7612850. DOI: 10.1038/s41586-018-0698-6. View

17.

Noel F, Massenet-Regad L, Carmi-Levy I, Cappuccio A, Grandclaudon M, Trichot C . Dissection of intercellular communication using the transcriptome-based framework ICELLNET. Nat Commun. 2021; 12(1):1089. PMC: 7889941. DOI: 10.1038/s41467-021-21244-x. View

18.

Browaeys R, Saelens W, Saeys Y . NicheNet: modeling intercellular communication by linking ligands to target genes. Nat Methods. 2019; 17(2):159-162. DOI: 10.1038/s41592-019-0667-5. View

19.

Rao A, Barkley D, Franca G, Yanai I . Exploring tissue architecture using spatial transcriptomics. Nature. 2021; 596(7871):211-220. PMC: 8475179. DOI: 10.1038/s41586-021-03634-9. View

20.

Walter R, Sonnentag S, Munoz-Sagredo L, Merkel M, Richert L, Bunert F . Wnt signaling is boosted during intestinal regeneration by a CD44-positive feedback loop. Cell Death Dis. 2022; 13(2):168. PMC: 8861016. DOI: 10.1038/s41419-022-04607-0. View