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Abstract

Overlaying omics data onto spatial biological dimensions has been a promising technology to provide high-resolution insights into the interactome and cellular heterogeneity relative to the organization of the molecular microenvironment of tissue samples in normal and disease states. Spatial omics can be categorized into three major modalities: () next-generation sequencing–based assays, () imaging-based spatially resolved transcriptomics approaches including in situ hybridization/in situ sequencing, and () imaging-based spatial proteomics. These modalities allow assessment of transcripts and proteins at a cellular level, generating large and computationally challenging datasets. The lack of standardized computational pipelines to analyze and integrate these nonuniform structured data has made it necessary to apply artificial intelligence and machine learning strategies to best visualize and translate their complexity. In this review, we summarize the currently available techniques and computational strategies, highlight their advantages and limitations, and discuss their future prospects in the scientific field.

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2024-08-23
2024-12-10
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Literature Cited

  1. 1.
    Li Z, Peng G. 2022.. Spatial transcriptomics: new dimension of understanding biological complexity. . Biophys. Rep. 8::11935
    [Crossref] [Google Scholar]
  2. 2.
    Ståhl PL, Salmén F, Vickovic S, Lundmark A, Navarro JF, et al. 2016.. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. . Science 353::7882
    [Crossref] [Google Scholar]
  3. 3.
    Salmén F, Ståhl PL, Mollbrink A, Navarro JF, Vickovic S, et al. 2018.. Barcoded solid-phase RNA capture for Spatial Transcriptomics profiling in mammalian tissue sections. . Nat. Protoc. 13::250134
    [Crossref] [Google Scholar]
  4. 4.
    Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E, et al. 2019.. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. . Science 363::146367
    [Crossref] [Google Scholar]
  5. 5.
    Vickovic S, Eraslan G, Salmén F, Klughammer J, Stenbeck L, et al. 2019.. High-definition spatial transcriptomics for in situ tissue profiling. . Nat. Methods 16::98790
    [Crossref] [Google Scholar]
  6. 6.
    Chen A, Liao S, Cheng M, Ma K, Wu L, et al. 2022.. Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays. . Cell 185::177792.e21
    [Crossref] [Google Scholar]
  7. 7.
    Shi J, Pan Y, Liu X, Cao W, Mu Y, Zhu Q. 2023.. Spatial omics sequencing based on microfluidic array chips. . Biosensors 13::712
    [Crossref] [Google Scholar]
  8. 8.
    Amarasinghe SL, Su S, Dong X, Zappia L, Ritchie ME, Gouil Q. 2020.. Opportunities and challenges in long-read sequencing data analysis. . Genome Biol. 21::30
    [Crossref] [Google Scholar]
  9. 9.
    Maynard KR, Collado-Torres L, Weber LM, Uytingco C, Barry BK, et al. 2021.. Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex. . Nat. Neurosci. 24::42536
    [Crossref] [Google Scholar]
  10. 10.
    Nagasawa S, Kuze Y, Maeda I, Kojima Y, Motoyoshi A, et al. 2021.. Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast. . Commun. Biol. 4::438
    [Crossref] [Google Scholar]
  11. 11.
    Gouin KH III, Ing N, Plummer JT, Rosser CJ, Ben Cheikh B, et al. 2021.. An N-Cadherin 2 expressing epithelial cell subpopulation predicts response to surgery, chemotherapy and immunotherapy in bladder cancer. . Nat. Commun. 12::4906
    [Crossref] [Google Scholar]
  12. 12.
    Chen S, Chang Y, Li L, Acosta D, Li Y, et al. 2022.. Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer's disease. . Acta Neuropathol. Commun. 10::188
    [Crossref] [Google Scholar]
  13. 13.
    Stickels RR, Murray E, Kumar P, Li J, Marshall JL, et al. 2021.. Highly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2. . Nat. Biotechnol. 39::31319
    [Crossref] [Google Scholar]
  14. 14.
    Zhou Y, Jia E, Pan M, Zhao X, Ge Q. 2020.. Encoding method of single-cell spatial transcriptomics sequencing. . Int. J. Biol. Sci. 16::266374
    [Crossref] [Google Scholar]
  15. 15.
    Russell AJ, Weir JA, Nadaf NM, Shabet M, Kumar V, et al. 2023.. Slide-tags: scalable, single-nucleus barcoding for multi-modal spatial genomics. . bioRxiv 2023.04.01.535228. https://doi.org/10.1101/2023.04.01.535228
  16. 16.
    Wu Y, Cheng Y, Wang X, Fan J, Gao Q. 2022.. Spatial omics: navigating to the golden era of cancer research. . Clin. Transl. Med. 12::e696
    [Crossref] [Google Scholar]
  17. 17.
    Cho C-S, Xi J, Si Y, Park S-R, Hsu J-E, et al. 2021.. Microscopic examination of spatial transcriptome using Seq-Scope. . Cell 184::355972.e22
    [Crossref] [Google Scholar]
  18. 18.
    Bressan D, Battistoni G, Hannon GJ. 2023.. The dawn of spatial omics. . Science 381::eabq4964
    [Crossref] [Google Scholar]
  19. 19.
    Fu X, Sun L, Dong R, Chen JY, Silakit R, et al. 2022.. Polony gels enable amplifiable DNA stamping and spatial transcriptomics of chronic pain. . Cell 185::462133.e17
    [Crossref] [Google Scholar]
  20. 20.
    Yu N, Jin Z, Liang C, Zhang J, Yang B. 2023.. Well-ST-seq: cost-effective spatial transcriptomics at cellular level and high RNA capture efficiency. . bioRxiv 2023.06.28.546974. https://doi.org/10.1101/2023.06.28.546974
  21. 21.
    Liu Y, Yang M, Deng Y, Su G, Enninful A, et al. 2020.. High-spatial-resolution multi-omics sequencing via deterministic barcoding in tissue. . Cell 183::166581.e18
    [Crossref] [Google Scholar]
  22. 22.
    Vandereyken K, Sifrim A, Thienpont B, Voet T. 2023.. Methods and applications for single-cell and spatial multi-omics. . Nat. Rev. Genet. 24::494515
    [Crossref] [Google Scholar]
  23. 23.
    Loppi SH, Tavera-Garcia MA, Becktel DA, Maiyo BK, Johnson KE, et al. 2023.. Increased fatty acid metabolism and decreased glycolysis are hallmarks of metabolic reprogramming within microglia in degenerating white matter during recovery from experimental stroke. . J. Cereb. Blood Flow Metab. 43::1099114
    [Crossref] [Google Scholar]
  24. 24.
    Walentynowicz KA, Engelhardt D, Cristea S, Yadav S, Onubogu U, et al. 2023.. Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma. . Cell Rep. 42::112235
    [Crossref] [Google Scholar]
  25. 25.
    Gupta S, Zugazagoitia J, Martinez-Morilla S, Fuhrman K, Rimm DL. 2020.. Digital quantitative assessment of PD-L1 using digital spatial profiling. . Lab. Investig. 100::131117
    [Crossref] [Google Scholar]
  26. 26.
    Bonnett SA, Rosenbloom AB, Ong GT, Conner M, Rininger AB, et al. 2023.. Ultra high-plex spatial proteogenomic investigation of giant cell glioblastoma multiforme immune infiltrates reveals distinct protein and RNA expression profiles. . Cancer Res. Commun. 3::76379
    [Crossref] [Google Scholar]
  27. 27.
    Kim Y, Danaher P, Cimino PJ, Hurth K, Warren S, et al. 2023.. Highly multiplexed spatially resolved proteomic and transcriptional profiling of the glioblastoma microenvironment using archived formalin-fixed paraffin-embedded specimens. . Mod. Pathol. 36::100034
    [Crossref] [Google Scholar]
  28. 28.
    Cheng M, Jiang Y, Xu J, Mentis A-FA, Wang S, et al. 2023.. Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges. . J. Genet. Genom. 50::62540
    [Crossref] [Google Scholar]
  29. 29.
    Larsson L, Frisén J, Lundeberg J. 2021.. Spatially resolved transcriptomics adds a new dimension to genomics. . Nat. Methods 18::1518
    [Crossref] [Google Scholar]
  30. 30.
    Jamalzadeh S, Häkkinen A, Andersson N, Huhtinen K, Laury A, et al. 2022.. QuantISH: RNA in situ hybridization image analysis framework for quantifying cell type-specific target RNA expression and variability. . Lab. Investig. 102::75361
    [Crossref] [Google Scholar]
  31. 31.
    Chen KH, Boettiger AN, Moffitt JR, Wang S, Zhuang X. 2015.. Spatially resolved, highly multiplexed RNA profiling in single cells. . Science 348::aaa6090
    [Crossref] [Google Scholar]
  32. 32.
    Pichon X, Lagha M, Mueller F, Bertrand E. 2018.. A growing toolbox to image gene expression in single cells: sensitive approaches for demanding challenges. . Mol. Cell 71::46880
    [Crossref] [Google Scholar]
  33. 33.
    Moffitt JR, Hao J, Bambah-Mukku D, Lu T, Dulac C, Zhuang X. 2016.. High-performance multiplexed fluorescence in situ hybridization in culture and tissue with matrix imprinting and clearing. . PNAS 113::1445661
    [Crossref] [Google Scholar]
  34. 34.
    Safieddine A, Coleno E, Lionneton F, Traboulsi A-M, Salloum S, et al. 2023.. HT-smFISH: a cost-effective and flexible workflow for high-throughput single-molecule RNA imaging. . Nat. Protoc. 18::15787
    [Crossref] [Google Scholar]
  35. 35.
    Yu C-C, Barry NC, Wassie AT, Sinha A, Bhattacharya A, et al. 2020.. Expansion microscopy of C. elegans. . eLife 9::e46249
    [Crossref] [Google Scholar]
  36. 36.
    Chen A, Sun Y, Lei Y, Li C, Liao S, et al. 2023.. Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex. . Cell 186::372643.e24
    [Crossref] [Google Scholar]
  37. 37.
    Lohoff T, Ghazanfar S, Missarova A, Koulena N, Pierson N, et al. 2022.. Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis. . Nat. Biotechnol. 40::7485
    [Crossref] [Google Scholar]
  38. 38.
    Shah S, Lubeck E, Zhou W, Cai L. 2016.. In situ transcription profiling of single cells reveals spatial organization of cells in the mouse hippocampus. . Neuron 92::34257
    [Crossref] [Google Scholar]
  39. 39.
    Lubeck E, Coskun AF, Zhiyentayev T, Ahmad M, Cai L. 2014.. Single-cell in situ RNA profiling by sequential hybridization. . Nat. Methods 11::36061
    [Crossref] [Google Scholar]
  40. 40.
    Lubeck E, Cai L. 2012.. Single-cell systems biology by super-resolution imaging and combinatorial labeling. . Nat. Methods 9::74348
    [Crossref] [Google Scholar]
  41. 41.
    Eng C-HL, Lawson M, Zhu Q, Dries R, Koulena N, et al. 2019.. Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH+. . Nature 568::23539
    [Crossref] [Google Scholar]
  42. 42.
    Betzig E, Patterson GH, Sougrat R, Lindwasser OW, Olenych S, et al. 2006.. Imaging intracellular fluorescent proteins at nanometer resolution. . Science 313::164245
    [Crossref] [Google Scholar]
  43. 43.
    Thompson RE, Larson DR, Webb WW. 2002.. Precise nanometer localization analysis for individual fluorescent probes. . Biophys. J. 82::277583
    [Crossref] [Google Scholar]
  44. 44.
    Xia C, Fan J, Emanuel G, Hao J, Zhuang X. 2019.. Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression. . PNAS 116::1949099
    [Crossref] [Google Scholar]
  45. 45.
    Wang G, Moffitt JR, Zhuang X. 2018.. Multiplexed imaging of high-density libraries of RNAs with MERFISH and expansion microscopy. . Sci. Rep. 8::4847
    [Crossref] [Google Scholar]
  46. 46.
    Liu J, Tran V, Vemuri VNP, Byrne A, Borja M, et al. 2023.. Concordance of MERFISH spatial transcriptomics with bulk and single-cell RNA sequencing. . Life Sci. Alliance 6::e202201701
    [Crossref] [Google Scholar]
  47. 47.
    Fang R, Halpern AR, Rahman MM, Huang Z, Lei Z, et al. 2023.. Three-dimensional single-cell transcriptome imaging of thick tissues. . bioRxiv 2023.07.21.550124. https://doi.org/10.1101/2023.07.21.550124
  48. 48.
    Crosetto N, Bienko M, Van Oudenaarden A. 2015.. Spatially resolved transcriptomics and beyond. . Nat. Rev. Genet. 16::5766
    [Crossref] [Google Scholar]
  49. 49.
    Shah S, Lubeck E, Zhou W, Cai L. 2017.. seqFISH accurately detects transcripts in single cells and reveals robust spatial organization in the hippocampus. . Neuron 94::75258.e1
    [Crossref] [Google Scholar]
  50. 50.
    Cai L, Eng CHL. 2019.. RNA seqFISH+ supplementary protocol. . Protocol Exchange. https://doi.org/10.1038/protex.2019.019
    [Google Scholar]
  51. 51.
    Zheng B, Fang L. 2022.. Spatially resolved transcriptomics provide a new method for cancer research. . J. Exp. Clin. Cancer Res. 41::179
    [Crossref] [Google Scholar]
  52. 52.
    Ke R, Mignardi M, Pacureanu A, Svedlund J, Botling J, et al. 2013.. In situ sequencing for RNA analysis in preserved tissue and cells. . Nat. Methods 10::85760
    [Crossref] [Google Scholar]
  53. 53.
    Wang X, Allen WE, Wright MA, Sylwestrak EL, Samusik N, et al. 2018.. Three-dimensional intact-tissue sequencing of single-cell transcriptional states. . Science 361::eaat5691
    [Crossref] [Google Scholar]
  54. 54.
    Rao A, Barkley D, França GS, Yanai I. 2021.. Exploring tissue architecture using spatial transcriptomics. . Nature 596::21120
    [Crossref] [Google Scholar]
  55. 55.
    Janesick A, Shelansky R, Gottscho AD, Wagner F, Rouault M, et al. 2022.. High resolution mapping of the breast cancer tumor microenvironment using integrated single cell, spatial and in situ analysis of FFPE tissue. . bioRxiv 2022.10.06.510405. https://doi.org/10.1101/2022.10.06.510405
  56. 56.
    Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Ferrante TC, et al. 2015.. Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact cells and tissues. . Nat. Protoc. 10::44258
    [Crossref] [Google Scholar]
  57. 57.
    Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Yang JL, et al. 2014.. Highly multiplexed subcellular RNA sequencing in situ. . Science 343::136063
    [Crossref] [Google Scholar]
  58. 58.
    He S, Bhatt R, Brown C, Brown EA, Buhr DL, et al. 2022.. High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging. . Nat. Biotechnol. 40::1794806
    [Crossref] [Google Scholar]
  59. 59.
    He S, Bhatt R, Birditt B, Brown C, Brown E, et al. 2021.. High-plex multiomic analysis in FFPE tissue at single-cellular and subcellular resolution by spatial molecular imaging. . bioRxiv 2021.11.03.467020. https://doi.org/10.1101/2021.11.03.467020
  60. 60.
    Gaudet S, Miller-Jensen K. 2016.. Redefining signaling pathways with an expanding single-cell toolbox. . Trends Biotechnol. 34::45869
    [Crossref] [Google Scholar]
  61. 61.
    Lin JR, Fallahi-Sichani M, Chen JY, Sorger PK. 2016.. Cyclic immunofluorescence (CycIF), a highly multiplexed method for single-cell imaging. . Curr. Protocols Chem. Biol. 8::25164
    [Crossref] [Google Scholar]
  62. 62.
    Hsieh W-C, Budiarto BR, Wang Y-F, Lin C-Y, Gwo M-C, et al. 2022.. Spatial multi-omics analyses of the tumor immune microenvironment. . J. Biomed. Sci. 29::96
    [Crossref] [Google Scholar]
  63. 63.
    Allam M, Cai S, Coskun AF. 2020.. Multiplex bioimaging of single-cell spatial profiles for precision cancer diagnostics and therapeutics. . NPJ Precis. Oncol. 4::11
    [Crossref] [Google Scholar]
  64. 64.
    Lin J-R, Izar B, Wang S, Yapp C, Mei S, et al. 2018.. Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes. . eLife 7::e31657
    [Crossref] [Google Scholar]
  65. 65.
    Sims Z, Mills GB, Chang YH. 2023.. MIM-CyCIF: masked imaging modeling for enhancing cyclic immunofluorescence (CyCIF) with panel reduction and imputation. . bioRxiv 2023.05.10.540265. https://doi.org/10.1101/2023.05.10.540265
  66. 66.
    Eng J, Bucher E, Hu Z, Zheng T, Gibbs SL, et al. 2022.. A framework for multiplex imaging optimization and reproducible analysis. . Commun. Biol. 5::438
    [Crossref] [Google Scholar]
  67. 67.
    Parra ER. 2018.. Novel platforms of multiplexed immunofluorescence for study of paraffin tumor tissues. . J. Cancer Treat. Diagn. 2::4353
    [Crossref] [Google Scholar]
  68. 68.
    Schubert W, Bonnekoh B, Pommer AJ, Philipsen L, Böckelmann R, et al. 2006.. Analyzing proteome topology and function by automated multidimensional fluorescence microscopy. . Nat. Biotechnol. 24::127078
    [Crossref] [Google Scholar]
  69. 69.
    Abraham MJ, Goncalves C, McCallum P, Gupta V, Preston SE, et al. 2023.. Tunable PhenoCycler imaging of the murine pre-clinical tumour microenvironments. . bioRxiv 2023.09.18.558299. https://doi.org/10.1101/2023.09.18.558299
  70. 70.
    Black S, Phillips D, Hickey JW, Kennedy-Darling J, Venkataraaman VG, et al. 2021.. CODEX multiplexed tissue imaging with DNA-conjugated antibodies. . Nat. Protoc. 16::380235
    [Crossref] [Google Scholar]
  71. 71.
    Kinkhabwala A, Herbel C, Pankratz J, Yushchenko DA, Rüberg S, et al. 2022.. MACSima imaging cyclic staining (MICS) technology reveals combinatorial target pairs for CAR T cell treatment of solid tumors. . Sci. Rep. 12::1911
    [Crossref] [Google Scholar]
  72. 72.
    Chang Q, Ornatsky OI, Siddiqui I, Loboda A, Baranov VI, Hedley DW. 2017.. Imaging mass cytometry. . Cytometry Part A 91::16069
    [Crossref] [Google Scholar]
  73. 73.
    Tracey LJ, An Y, Justice MJ. 2021.. CyTOF: an emerging technology for single-cell proteomics in the mouse. . Curr. Protoc. 1::e118
    [Crossref] [Google Scholar]
  74. 74.
    Hie B, Bryson B, Berger B. 2019.. Efficient integration of heterogeneous single-cell transcriptomes using Scanorama. . Nat. Biotechnol. 37::68591
    [Crossref] [Google Scholar]
  75. 75.
    Bonnevier J, Hammerbeck C, Goetz C. 2018.. Flow cytometry: definition, history, and uses in biological research. . In Flow Cytometry Basics for the Non-Expert, , pp. 111. Cham:: Springer
    [Google Scholar]
  76. 76.
    Gadalla R, Noamani B, MacLeod BL, Dickson RJ, Guo M, et al. 2019.. Validation of CyTOF against flow cytometry for immunological studies and monitoring of human cancer clinical trials. . Front. Oncol. 9::415
    [Crossref] [Google Scholar]
  77. 77.
    Tan WCC, Nerurkar SN, Cai HY, Ng HHM, Wu D, et al. 2020.. Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy. . Cancer Commun. 40::13553
    [Crossref] [Google Scholar]
  78. 78.
    Carstensen S, Holz O, Hohlfeld JM, Müller M. 2021.. Quantitative analysis of endotoxin-induced inflammation in human lung cells by Chipcytometry. . Cytometry Part A 99::96776
    [Crossref] [Google Scholar]
  79. 79.
    Ptacek J, Locke D, Finck R, Cvijic M-E, Li Z, et al. 2020.. Multiplexed ion beam imaging (MIBI) for characterization of the tumor microenvironment across tumor types. . Lab. Investig. 100::111123
    [Crossref] [Google Scholar]
  80. 80.
    Baharlou H, Canete NP, Cunningham AL, Harman AN, Patrick E. 2019.. Mass cytometry imaging for the study of human diseases—applications and data analysis strategies. . Front. Immunol. 10::2657
    [Crossref] [Google Scholar]
  81. 81.
    Angelo M, Bendall SC, Finck R, Hale MB, Hitzman C, et al. 2014.. Multiplexed ion beam imaging of human breast tumors. . Nat. Med. 20::43642
    [Crossref] [Google Scholar]
  82. 82.
    Elaldi R, Hemon P, Petti L, Cosson E, Desrues B, et al. 2021.. High dimensional imaging mass cytometry panel to visualize the tumor immune microenvironment contexture. . Front. Immunol. 12::666233
    [Crossref] [Google Scholar]
  83. 83.
    Kakade VR, Weiss M, Cantley LG. 2021.. Using imaging mass cytometry to define cell identities and interactions in human tissues. . Front. Physiol. 12::817181
    [Crossref] [Google Scholar]
  84. 84.
    Glasson Y, Chépeaux L-A, Dumé A-S, Lafont V, Faget J, et al. 2023.. Single-cell high-dimensional imaging mass cytometry: one step beyond in oncology. . Semin. Immunopathol. 45::1728
    [Google Scholar]
  85. 85.
    Le Rochais M, Hemon P, Pers J-O, Uguen A. 2022.. Application of high-throughput imaging mass cytometry Hyperion in cancer research. . Front. Immunol. 13::859414
    [Crossref] [Google Scholar]
  86. 86.
    Baars MJ, Sinha N, Amini M, Pieterman-Bos A, van Dam S, et al. 2021.. MATISSE: a method for improved single cell segmentation in imaging mass cytometry. . BMC Biol. 19::99
    [Crossref] [Google Scholar]
  87. 87.
    Collette A. 2013.. Python and HDF5: Unlocking Scientific Data. Beijing:: O'Reilly
    [Google Scholar]
  88. 88.
    Schneider CA, Rasband WS, Eliceiri KW. 2012.. NIH Image to ImageJ: 25 years of image analysis. . Nat. Methods 9::67175
    [Crossref] [Google Scholar]
  89. 89.
    Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, et al. 2017.. QuPath: open source software for digital pathology image analysis. . Sci. Rep. 7::16878
    [Crossref] [Google Scholar]
  90. 90.
    Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, et al. 2019.. Fast, sensitive and accurate integration of single-cell data with Harmony. . Nat. Methods 16::128996
    [Crossref] [Google Scholar]
  91. 91.
    Polański K, Young MD, Miao Z, Meyer KB, Teichmann SA, Park J-E. 2020.. BBKNN: fast batch alignment of single cell transcriptomes. . Bioinformatics 36::96465
    [Crossref] [Google Scholar]
  92. 92.
    Greenswald NF, Miller G, Moen E, Kong A, Kagel A, et al. 2022.. Whole-cell segmentation of tissue images with human-level performance using large-scale data annotation and deep learning. . Nat. Biotechnol. 40::55565
    [Crossref] [Google Scholar]
  93. 93.
    Schmidt U, Weigert M, Broaddus C, Myers G. 2018.. Cell detection with star-convex polygons. arXiv:1806.03535 [cs.CV]
  94. 94.
    Stringer C, Wang T, Michaelos M, Pachitariu M. 2021.. Cellpose: a generalist algorithm for cellular segmentation. . Nat. Methods 18::1006
    [Crossref] [Google Scholar]
  95. 95.
    Humphries M, Maxwell P, Salto-Tellez M. 2021.. QuPath: the global impact of an open source digital pathology system. . Comput. Struct. Biotechnol. J. 19::85259
    [Crossref] [Google Scholar]
  96. 96.
    Bakshi A, Iturra FE, Alamban A, Rosas-Salvans M, Dumont S, Aydogan MG. 2022.. Cytoplasmic divisions without nuclei. . bioRxiv 2022.06.15.496343. https://doi.org/10.1101/2022.06.15.496343
  97. 97.
    Hafemeister C, Satija R. 2019.. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. . Genome Biol. 20::296
    [Crossref] [Google Scholar]
  98. 98.
    Saiselet M, Rodrigues-Vitória J, Tourneur A, Craciun L, Spinette A, et al. 2020.. Transcriptional output, cell-type densities, and normalization in spatial transcriptomics. . J. Mol. Cell Biol. 12::9068
    [Crossref] [Google Scholar]
  99. 99.
    Shang L, Zhou X. 2022.. Spatially aware dimension reduction for spatial transcriptomics. . Nat. Commun. 13::7203
    [Crossref] [Google Scholar]
  100. 100.
    Palla G, Spitzer H, Klein M, Fischer D, Schaar AC, et al. 2022.. Squidpy: a scalable framework for spatial omics analysis. . Nat. Methods 19::17178
    [Crossref] [Google Scholar]
  101. 101.
    Wu Z, Kondo A, McGrady M, Baker EA, Wu E, et al. 2023.. Characterizing tissue structures from spatial omics with spatial cellular graph partition. . bioRxiv 2023.09.05.556133. https://doi.org/10.1101/2023.09.05.556133
  102. 102.
    Yip SH, Sham PC, Wang J. 2019.. Evaluation of tools for highly variable gene discovery from single-cell RNA-seq data. . Brief. Bioinform. 20::158389
    [Crossref] [Google Scholar]
  103. 103.
    Zhang K, Feng W, Wang P. 2022.. Identification of spatially variable genes with graph cuts. . Nat. Commun. 13::5488
    [Crossref] [Google Scholar]
  104. 104.
    Hubert LJ, Golledge RG, Costanzo CM. 1981.. Generalized procedures for evaluating spatial autocorrelation. . Geogr. Anal. 13::22433
    [Crossref] [Google Scholar]
  105. 105.
    Laruelle E, Spassky N, Genovesio A. 2020.. Unraveling spatial cellular pattern by computational tissue shuffling. . Commun. Biol. 3::605
    [Crossref] [Google Scholar]
  106. 106.
    Summers HD, Wills JW, Rees P. 2022.. Spatial statistics is a comprehensive tool for quantifying cell neighbor relationships and biological processes via tissue image analysis. . Cell Rep. Methods 2::100348
    [Crossref] [Google Scholar]
  107. 107.
    Berry S, Giraldo NA, Green BF, Cottrell TR, Stein JE, et al. 2021.. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade. . Science 372::eaba2609
    [Crossref] [Google Scholar]
  108. 108.
    Li X, Xiao C, Qi J, Xue W, Xu X, et al. 2023.. STellaris: a web server for accurate spatial mapping of single cells based on spatial transcriptomics data. . Nucleic Acids Res. 51::W56068
    [Crossref] [Google Scholar]
  109. 109.
    Kleshchevnikov V, Shmatko A, Dann E, Aivazidis A, King HW, et al. 2022.. Cell2location maps fine-grained cell types in spatial transcriptomics. . Nat. Biotechnol. 40::66171
    [Crossref] [Google Scholar]
  110. 110.
    Martin PC, Kim H, Lövkvist C, Hong BW, Won KJ. 2022.. Vesalius: high-resolution in silico anatomization of spatial transcriptomic data using image analysis. . Mol. Syst. Biol. 18::e11080
    [Crossref] [Google Scholar]
  111. 111.
    Liu X, Zeira R, Raphael BJ. 2023.. PASTE2: partial alignment of multi-slice spatially resolved transcriptomics data. . bioRxiv 2023.01.08.523162. https://doi.org/10.1101/2023.01.08.523162
  112. 112.
    Liu W, Liao X, Luo Z, Yang Y, Lau MC, et al. 2023.. Probabilistic embedding, clustering, and alignment for integrating spatial transcriptomics data with PRECAST. . Nat. Commun. 14::296
    [Crossref] [Google Scholar]
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