Spatial biology is the study of biomolecules and cells in their native three-dimensional context. Spatial biology encompasses different levels of cellular resolution including (1) subcellular localization of DNA, RNA, and proteins, (2) single-cell resolution and in situ communications like cell-cell interactions and cell signaling, (3) cellular neighborhoods, regions, or microenvironments, and (4) tissue architecture and organization in organs. Dysregulation of tissue organization is a common feature in human disease progression including tumorigenesis and neurodegeneration. Many fields within biology are studied for their individual contribution to spatial biology.

Spatial transcriptomics

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Spatial transcriptomics measures mRNA transcript abundance and distribution in situ across a tissue.[1] Spatial method for RNA in situ detection is first described in a 1969 landmark paper[2] by Joseph G. Gall and Mary-Lou Pardue. Previous to spatial transcriptomics techniques, whole transcriptome profiling lacked spatial context because tissues were ground up in bulk RNA-seq or dissociated into single cells suspensions in single cell RNA-seq. Although some literature refers to "spatial genomics" for RNA[3], growing consensus has settled on usage of "spatial transcriptomics" or "spatially resolved transcriptomics."[4]

Spatial proteomics

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Spatial proteomics measures the localization and abundance of proteins at the subcellular level across a tissue.[5] Immunohistochemistry-based spatial proteomic methods include oligo barcoded antibodies, cyclic immunofluorescence (cycIF), co-detection by indexing (CODEX), iterative bleaching extends multiplicity (IBEX), multiplexed ion beam imaging (MIBI) and imaging mass cytometry (IMC)[6]. Other methods includes deep visual proteomics that profile protein expression in single cells by laser capture microdissection and mass spectroscopy. The term "spatial medicine" is recently coined by Eric Topol to refer to a study that used deep visual proteomics to find a therapeutic treatment for patients with a rare skin condition.[7]

Spatial genomics

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Spatial genomics localizes the native three dimensional genome architecture within the nucleus[8]. Nuclear organization of chromosomes and how chromosomes are positioned and folded has implications for gene regulation, transcription, DNA replication, DNA damage repair, and cell division.

Spatial omics vs Spatial Biology

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Spatial omics refers to the collection of high-throughput molecular profiling techniques that measure and spatially map the distribution of transcriptome, proteome or other biomolecules in a tissue. Spatial biology is a more general term that encompasses the science and techniques, but often spatial biology and spatial omics are used interchangeably.

References

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  1. ^ Jena, Siddhartha G.; Verma, Archit; Engelhardt, Barbara E. (4 September 2024). "Answering open questions in biology using spatial genomics and structured methods". BMC Bioinformatics. 25 (1): 291. doi:10.1186/s12859-024-05912-5. PMC 11375982. PMID 39232666.
  2. ^ Gall, Joseph G.; Pardue, Mary Lou (June 1969). "Formation and detection of rna-dna hybrid molecules in cytological preparations*". Proceedings of the National Academy of Sciences. 63 (2): 378–383. Bibcode:1969PNAS...63..378G. doi:10.1073/pnas.63.2.378. PMC 223575. PMID 4895535.
  3. ^ Jena, Siddhartha G.; Verma, Archit; Engelhardt, Barbara E. (2024-09-04). "Answering open questions in biology using spatial genomics and structured methods". BMC Bioinformatics. 25 (1). doi:10.1186/s12859-024-05912-5. ISSN 1471-2105. PMC 11375982. PMID 39232666.
  4. ^ Marx, Vivien (January 2021). "Method of the Year: spatially resolved transcriptomics". Nature Methods. 18 (1): 9–14. doi:10.1038/s41592-020-01033-y. ISSN 1548-7105.
  5. ^ Lundberg, Emma; Borner, Georg H. H. (May 2019). "Spatial proteomics: a powerful discovery tool for cell biology". Nature Reviews Molecular Cell Biology. 20 (5): 285–302. doi:10.1038/s41580-018-0094-y. PMID 30659282.
  6. ^ "Method of the Year 2024: spatial proteomics". Nature Methods. 21 (12): 2195–2196. December 2024. doi:10.1038/s41592-024-02565-3. ISSN 1548-7105.
  7. ^ Topol, Eric (2024-10-26). "The Dawn of Spatial Medicine". Ground Truths. Retrieved 2025-01-04.
  8. ^ Kempfer, Rieke; Pombo, Ana (April 2020). "Methods for mapping 3D chromosome architecture". Nature Reviews Genetics. 21 (4): 207–226. doi:10.1038/s41576-019-0195-2. ISSN 1471-0064.