Answering open questions in biology using spatial genomics and structured methods | BMC Bioinformatics

Mazzarello P. A unifying concept: the history of cell theory. Nat Cell Biol. 1999;1(1):13–5.Article 

Google Scholar 
Fujiki Y, Hubbard AL, Fowler S, Lazarow PB. Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum. J Cell Biol. 1982;93(1):97–102.Article 
CAS 
PubMed 

Google Scholar 
Ehrenreich J, Bergeron J, Siekevitz P, Palade G. Golgi fractions prepared from rat liver homogenates: I. isolation procedure and morphological characterization. J Cell Biol. 1973;59(1):45–72.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Koster AJ, Klumperman J. Electron microscopy in cell biology: integrating structure and function. Nat Rev Mol Cell Biol. 2003;4(9):6–9; SUPP.
Google Scholar 
Hansma PK, Tersoff J. Scanning tunneling microscopy. J Appl Phys. 1987;61(2):1–24.Article 

Google Scholar 
Alonso JL, Goldmann WH. Feeling the forces: atomic force microscopy in cell biology. Life Sci. 2003;72(23):2553–60.Article 
CAS 
PubMed 

Google Scholar 
Schermelleh L, Ferrand A, Huser T, Eggeling C, Sauer M, Biehlmaier O, Drummen GP. Super-resolution microscopy demystified. Nat Cell Biol. 2019;21(1):72–84.Article 
CAS 
PubMed 

Google Scholar 
McGettigan PA. Transcriptomics in the rna-seq era. Curr Opin Chem Biol. 2013;17(1):4–11.Article 
CAS 
PubMed 

Google Scholar 
Kulkarni A, Anderson AG, Merullo DP, Konopka G. Beyond bulk: a review of single cell transcriptomics methodologies and applications. Curr Opin Biotechnol. 2019;58:129–36.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ash JT, Darnell G, Munro D, Engelhardt BE. Joint analysis of expression levels and histological images identifies genes associated with tissue morphology. Nat Commun. 2021;12(1):1609.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Schmauch B, Romagnoni A, Pronier E, Saillard C, Maillé P, Calderaro J, Kamoun A, Sefta M, Toldo S, Zaslavskiy M, et al. A deep learning model to predict RNA-Seq expression of tumours from whole slide images. Nat Commun. 2020;11(1):3877.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Comiter C, Vaishnav ED, Ciapmricotti M, Li B, Yang Y, Rodig SJ, Turner M, Pfaff KL, Jané-Valbuena J, Slyper M, et al. Inference of single cell profiles from histology stains with the single-cell omics from histology analysis framework (schaf). BioRxiv, 2023;2023–03.Rios Velazquez E, Parmar C, Liu Y, Coroller TP, Cruz G, Stringfield O, Ye Z, Makrigiorgos M, Fennessy F, Mak RH, et al. Somatic mutations drive distinct imaging phenotypes in lung cancersomatic mutations and radiomic phenotypes. Can Res. 2017;77(14):3922–30.Article 
CAS 

Google Scholar 
Levsky JM, Singer RH. Fluorescence in situ hybridization: past, present and future. J Cell Sci. 2003;116(14):2833–8.Article 
CAS 
PubMed 

Google Scholar 
Bouwman BA, Crosetto N, Bienko M. The era of 3d and spatial genomics. Trends Genet 2022Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E, Vanderburg CR, Welch J, Chen LM, Chen F, Macosko EZ. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science. 2019;363(6434):1463–7.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Payne AC, Chiang ZD, Reginato PL, Mangiameli SM, Murray EM, Yao C-C, Markoulaki S, Earl AS, Labade AS, Jaenisch R, et al. In situ genome sequencing resolves dna sequence and structure in intact biological samples. Science. 2021;371(6532):3446.Article 

Google Scholar 
Zhao T, Chiang ZD, Morriss JW, LaFave LM, Murray EM, Del Priore I, Meli K, Lareau CA, Nadaf NM, Li J, et al. Spatial genomics enables multi-modal study of clonal heterogeneity in tissues. Nature. 2022;601(7891):85–91.Article 
CAS 
PubMed 

Google Scholar 
Thul PJ, Åkesson L, Wiking M, Mahdessian D, Geladaki A, Ait Blal H, Alm T, Asplund A, Björk L, Breckels LM, et al. A subcellular map of the human proteome. Science. 2017;356(6340):3321.Article 

Google Scholar 
Van Holde KE. Chromatin. Berlin: Springer Science & Business Media; 2012.
Google Scholar 
Martincorena I, Campbell PJ. Somatic mutation in cancer and normal cells. Science. 2015;349(6255):1483–9.Article 
CAS 
PubMed 

Google Scholar 
Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128(4):635–8.Article 
CAS 
PubMed 

Google Scholar 
Jones PA, Takai D. The role of dna methylation in mammalian epigenetics. Science. 2001;293(5532):1068–70.Article 
CAS 
PubMed 

Google Scholar 
Das PM, Singal R. Dna methylation and cancer. J Clin Oncol. 2004;22(22):4632–42.Article 
CAS 
PubMed 

Google Scholar 
Meissner A, Gnirke A, Bell GW, Ramsahoye B, Lander ES, Jaenisch R. Reduced representation bisulfite sequencing for comparative high-resolution dna methylation analysis. Nucleic Acids Res. 2005;33(18):5868–77.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. Atac-seq: a method for assaying chromatin accessibility genome-wide. Curr Protoc Mol Biol. 2015;109(1):21–9.Article 
PubMed Central 

Google Scholar 
Belmont AS. Nuclear compartments: an incomplete primer to nuclear compartments, bodies, and genome organization relative to nuclear architecture. Cold Spring Harb Perspect Biol. 2022;14(7): 041268.Article 

Google Scholar 
Lieberman-Aiden E, Van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326(5950):289–93.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Fortin J-P, Hansen KD. Reconstructing a/b compartments as revealed by hi-c using long-range correlations in epigenetic data. Genome Biol. 2015;16(1):1–23.Article 
CAS 

Google Scholar 
Jones MJ, Goodman SJ, Kobor MS. Dna methylation and healthy human aging. Aging Cell. 2015;14(6):924–32.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Zampieri M, Ciccarone F, Calabrese R, Franceschi C, Bürkle A, Caiafa P. Reconfiguration of dna methylation in aging. Mech Ageing Dev. 2015;151:60–70.Article 
CAS 
PubMed 

Google Scholar 
Arceo XG, Koslover EF, Zid BM, Brown A. Translation kinetics and diffusive timescales regulate mitochondrial localization of mrnas in yeast and mammalian cells. Biophys J. 2023;122(3):300.Article 

Google Scholar 
Holt CE, Bullock SL. Subcellular mrna localization in animal cells and why it matters. Science. 2009;326(5957):1212–6.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lécuyer E, Yoshida H, Parthasarathy N, Alm C, Babak T, Cerovina T, Hughes TR, Tomancak P, Krause HM. Global analysis of mrna localization reveals a prominent role in organizing cellular architecture and function. Cell. 2007;131(1):174–87.Article 
PubMed 

Google Scholar 
Little SC, Tkačik G, Kneeland TB, Wieschaus EF, Gregor T. The formation of the bicoid morphogen gradient requires protein movement from anteriorly localized mrna. PLoS Biol. 2011;9(3):1000596.Article 

Google Scholar 
Laurent GS, Wahlestedt C, Kapranov P. The landscape of long noncoding rna classification. Trends Genet. 2015;31(5):239–51.Article 

Google Scholar 
McKellar DW, Mantri M, Hinchman MM, Parker JS, Sethupathy P, Cosgrove BD, De Vlaminck I. Spatial mapping of the total transcriptome by in situ polyadenylation. Nat Biotechnol. 2023;41(4):513–20.Article 
CAS 
PubMed 

Google Scholar 
Mateescu B, Jones JC, Alexander RP, Alsop E, An JY, Asghari M, Boomgarden A, Bouchareychas L, Cayota A, Chang H-C, et al. Phase 2 of extracellular rna communication consortium charts next-generation approaches for extracellular rna research. Iscience. 2022;25(8)Li J, Zhang Y, Yang C, Rong R. Discrepant mrna and protein expression in immune cells. Curr Genom. 2020;21(8):560–3.Article 
CAS 

Google Scholar 
Wang D. Discrepancy between mrna and protein abundance: insight from information retrieval process in computers. Comput Biol Chem. 2008;32(6):462–8.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Gry M, Rimini R, Strömberg S, Asplund A, Pontén F, Uhlén M, Nilsson P. Correlations between rna and protein expression profiles in 23 human cell lines. BMC Genom. 2009;10(1):1–14.Article 

Google Scholar 
Liu Y, Beyer A, Aebersold R. On the dependency of cellular protein levels on mrna abundance. Cell. 2016;165(3):535–50.Article 
CAS 
PubMed 

Google Scholar 
Krishna RG, Wold F. Post-translational modifications of proteins. Methods in protein sequence analysis, 1993;167–172.Gingras A-C, Abe KT, Raught B. Getting to know the neighborhood: using proximity-dependent biotinylation to characterize protein complexes and map organelles. Curr Opin Chem Biol. 2019;48:44–54.Article 
CAS 
PubMed 

Google Scholar 
Dunham WH, Mullin M, Gingras A-C. Affinity-purification coupled to mass spectrometry: Basic principles and strategies. Proteomics. 2012;12(10):1576–90.Article 
CAS 
PubMed 

Google Scholar 
Fries P. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence. Trends Cogn Sci. 2005;9(10):474–80.Article 
PubMed 

Google Scholar 
Shevach EM. Regulatory t cells in autoimmmunity. Annu Rev Immunol. 2000;18(1):423–49.Article 
CAS 
PubMed 

Google Scholar 
Woodcock EA, Matkovich SJ. Cardiomyocytes structure, function and associated pathologies. Int J Biochem Cell Biol. 2005;37(9):1746–51.Article 
CAS 
PubMed 

Google Scholar 
Domínguez Conde C, Xu C, Jarvis L, Rainbow D, Wells S, Gomes T, Howlett S, Suchanek O, Polanski K, King H, et al. Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science. 2022;376(6594):5197.Article 

Google Scholar 
Verhoeven BM, Mei S, Olsen TK, Gustafsson K, Valind A, Lindström A, Gisselsson D, Fard SS, Hagerling C, Kharchenko PV, et al. The immune cell atlas of human neuroblastoma. Cell Rep Med 3(6)2022;Raj A, Van Oudenaarden A. Nature, nurture, or chance: stochastic gene expression and its consequences. Cell. 2008;135(2):216–26.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Snijder B, Pelkmans L. Origins of regulated cell-to-cell variability. Nat Rev Mol Cell Biol. 2011;12(2):119–25.Article 
CAS 
PubMed 

Google Scholar 
Almet AA, Cang Z, Jin S, Nie Q. The landscape of cell-cell communication through single-cell transcriptomics. Curr Opin Syst Biol. 2021;26:12–23.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Nave K-A, Werner HB. Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol. 2014;30:503–33.Article 
CAS 
PubMed 

Google Scholar 
Baker NE. Emerging mechanisms of cell competition. Nat Rev Genet. 2020;21(11):683–97.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Liu S, Iorgulescu JB, Li S, Borji M, Barrera-Lopez IA, Shanmugam V, Lyu H, Morriss JW, Garcia ZN, Murray E, et al. Spatial maps of t cell receptors and transcriptomes reveal distinct immune niches and interactions in the adaptive immune response. Immunity. 2022;55(10):1940–52.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Marrahi AE, Lipreri F, Alber D, Hausser J. Four tumor micro-environmental niches explain a continuum of inter-patient variation in the macroscopic cellular composition of breast tumors. bioRxiv, 2022;2022–03.Medaglia C, Giladi A, Stoler-Barak L, De Giovanni M, Salame TM, Biram A, David E, Li H, Iannacone M, Shulman Z, et al. Spatial reconstruction of immune niches by combining photoactivatable reporters and scrna-seq. Science. 2017;358(6370):1622–6.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tikhonova AN, Lasry A, Austin R, Aifantis I. Cell-by-cell deconstruction of stem cell niches. Cell Stem Cell. 2020;27(1):19–34.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Mayer AT, Holman DR, Sood A, Tandon U, Bhate SS, Bodapati S, Barlow GL, Chang J, Black S, Crenshaw EC, et al. A tissue atlas of ulcerative colitis revealing evidence of sex-dependent differences in disease-driving inflammatory cell types and resistance to tnf inhibitor therapy. Sci Adv. 2023;9(3):1166.Article 

Google Scholar 
Pelka K, Hofree M, Chen JH, Sarkizova S, Pirl JD, Jorgji V, Bejnood A, Dionne D, William HG, Xu KH, et al. Spatially organized multicellular immune hubs in human colorectal cancer. Cell. 2021;184(18):4734–52.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Lane SW, Williams DA, Watt FM. Modulating the stem cell niche for tissue regeneration. Nat Biotechnol. 2014;32(8):795–803.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tepass U, Theres C, Knust E. crumbs encodes an egf-like protein expressed on apical membranes of drosophila epithelial cells and required for organization of epithelia. Cell. 1990;61(5):787–99.Article 
CAS 
PubMed 

Google Scholar 
Regev A, Teichmann S, Rozenblatt-Rosen O, Stubbington M, Ardlie K, Amit I, Arlotta P, Bader G, Benoist C, Biton M, et al. The human cell atlas white paper. arXiv preprint arXiv:1810.05192 2018;Shahan R, Hsu C-W, Nolan TM, Cole BJ, Taylor IW, Greenstreet L, Zhang S, Afanassiev A, Vlot AHC, Schiebinger G, et al. A single-cell arabidopsis root atlas reveals developmental trajectories in wild-type and cell identity mutants. Dev Cell. 2022;57(4):543–60.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Sikkema L, Ramírez-Suástegui C, Strobl DC, Gillett TE, Zappia L, Madissoon E, Markov NS, Zaragosi L-E, Ji Y, Ansari M, et al. An integrated cell atlas of the lung in health and disease. Nat Med 2023;1–15.Nguyen QH, Pervolarakis N, Blake K, Ma D, Davis RT, James N, Phung AT, Willey E, Kumar R, Jabart E, et al. Profiling human breast epithelial cells using single cell rna sequencing identifies cell diversity. Nat Commun. 2018;9(1):2028.Article 
PubMed 
PubMed Central 

Google Scholar 
Consortium TM, coordination Schaum Nicholas 1 Karkanias Jim 2 Neff Norma F. 2 May Andrew P. 2 Quake Stephen R. quake@ stanford. edu 2 3 f Wyss-Coray Tony twc@ stanford. edu 4 5 6 g Darmanis Spyros spyros. darmanis@ czbiohub. org 2 h, O., coordination Batson Joshua 2 Botvinnik Olga 2 Chen Michelle B. 3 Chen Steven 2 Green Foad 2 Jones Robert C. 3 Maynard Ashley 2 Penland Lolita 2 Pisco Angela Oliveira 2 Sit Rene V. 2 Stanley Geoffrey M. 3 Webber James T. 2 Zanini Fabio 3, L., data analysis Batson Joshua 2 Botvinnik Olga 2 Castro Paola 2 Croote Derek 3 Darmanis Spyros 2 DeRisi Joseph L. 2 27 Karkanias Jim 2 Pisco Angela Oliveira 2 Stanley Geoffrey M. 3 Webber James T. 2 Zanini Fabio 3, C.: Single-cell transcriptomics of 20 mouse organs creates a tabula muris. Nature 562(7727), 2018;367–372 .Hung R-J, Hu Y, Kirchner R, Liu Y, Xu C, Comjean A, Tattikota SG, Li F, Song W, Ho Sui S, et al. A cell atlas of the adult drosophila midgut. Proc Natl Acad Sci. 2020;117(3):1514–23.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Cao J, Packer JS, Ramani V, Cusanovich DA, Huynh C, Daza R, Qiu X, Lee C, Furlan SN, Steemers FJ, Adey A, Waterston RH, Trapnell C, Shendure J. Comprehensive single-cell transcriptional profiling of a multicellular organism. Science. 2017;357(6352):661–7. https://doi.org/10.1126/science.aam8940.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Taylor DM, Aronow BJ, Tan K, Bernt K, Salomonis N, Greene CS, Frolova A, Henrickson SE, Wells A, Pei L, et al. The pediatric cell atlas: defining the growth phase of human development at single-cell resolution. Dev Cell. 2019;49(1):10–29.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Chen D, Wang W, Wu L, Liang L, Wang S, Cheng Y, Zhang T, Chai C, Luo Q, Sun C, et al. Single-cell atlas of peripheral blood mononuclear cells from pregnant women. Clin Transl Med. 2022;12(5):821.Article 

Google Scholar 
Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martínez-Colón GJ, McKechnie JL, Ivison GT, Ranganath T, Vergara R, Hollis T, et al. A single-cell atlas of the peripheral immune response in patients with severe covid-19. Nat Med. 2020;26(7):1070–6.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Schiller HB, Montoro DT, Simon LM, Rawlins EL, Meyer KB, Strunz M, Vieira Braga FA, Timens W, Koppelman GH, Budinger GS, et al. The human lung cell atlas: a high-resolution reference map of the human lung in health and disease. Am J Respir Cell Mol Biol. 2019;61(1):31–41.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Zhou Y, Xu J, Hou Y, Bekris L, Leverenz JB, Pieper AA, Cummings J, Cheng F. The alzheimer’s cell atlas (taca): A single-cell molecular map for translational therapeutics accelerator in alzheimer’s disease. Alzheimer’s & Dementia: Transl Res Clin Interve. 2022;8(1):12350.
Google Scholar 
Grubman A, Chew G, Ouyang JF, Sun G, Choo XY, McLean C, Simmons RK, Buckberry S, Vargas-Landin DB, Poppe D, et al. A single-cell atlas of entorhinal cortex from individuals with alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat Neurosci. 2019;22(12):2087–97.Article 
CAS 
PubMed 

Google Scholar 
Winkler EA, Kim CN, Ross JM, Garcia JH, Gil E, Oh I, Chen LQ, Wu D, Catapano JS, Raygor K, et al. A single-cell atlas of the normal and malformed human brain vasculature. Science. 2022;375(6584):7377.Article 

Google Scholar 
Starling E. Discussion on the therapeutic value of hormones. Proceedings of the Royal Society of Medicine 7(Ther_Pharmacol). 1914;29–31.Nair A, Chauhan P, Saha B, Kubatzky KF. Conceptual evolution of cell signaling. Int J Mol Sci. 2019;20(13):3292.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Levi-Montalcini R, Hamburger V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool. 1951;116(2):321–61.Article 
CAS 
PubMed 

Google Scholar 
Hokin MR, Hokin LE. Enzyme secretion and the incorporation of p32 into phospholipides of pancreas slices. J Biol Chem. 1953;203(2):967–77.Article 
CAS 
PubMed 

Google Scholar 
Krebs EG, Fischer EH. The phosphorylase b to a converting enzyme of rabbit skeletal muscle. Biochem Biophys Acta. 1956;20:150–7.Article 
CAS 
PubMed 

Google Scholar 
Aoki K, Kumagai Y, Sakurai A, Komatsu N, Fujita Y, Shionyu C, Matsuda M. Stochastic erk activation induced by noise and cell-to-cell propagation regulates cell density-dependent proliferation. Mol Cell. 2013;52(4):529–40.Article 
CAS 
PubMed 

Google Scholar 
McFann SE, Shvartsman SY, Toettcher JE. Putting in the erk: Growth factor signaling and mesoderm morphogenesis. Curr Top Dev Biol. 2022;149:263–310.Article 
CAS 
PubMed 

Google Scholar 
Marmion RA, Simpkins AG, Barrett LA, Denberg DW, Zusman S, Schottenfeld-Roames J, Schüpbach T, Shvartsman SY. Stochastic phenotypes in ras-dependent developmental diseases. Curr Biol. 2023;33(5):807–16.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Green JB, Sharpe J. Positional information and reaction-diffusion: two big ideas in developmental biology combine. Development. 2015;142(7):1203–11.Article 
CAS 
PubMed 

Google Scholar 
Merle M, Messio L, Mozziconacci J. Turing-like patterns in an asymmetric dynamic ising model. Phys Rev E. 2019;100(4): 042111.Article 
CAS 
PubMed 

Google Scholar 
Breakspear M, Heitmann S, Daffertshofer A. Generative models of cortical oscillations: neurobiological implications of the kuramoto model. Front Hum Neurosci. 2010;4:190.Article 
PubMed 
PubMed Central 

Google Scholar 
Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. Optimal decoding of cellular identities in a genetic network. Cell. 2019;176(4):844–55.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Tkačik G, Callan CG Jr, Bialek W. Information flow and optimization in transcriptional regulation. Proc Natl Acad Sci. 2008;105(34):12265–70.Article 
PubMed 
PubMed Central 

Google Scholar 
Eng C-HL, Lawson M, Zhu Q, Dries R, Koulena N, Takei Y, Yun J, Cronin C, Karp C, Yuan G-C, et al. Transcriptome-scale super-resolved imaging in tissues by rna seqfish+. Nature. 2019;568(7751):235–9.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Yuan Y, Bar-Joseph Z. Gcng: graph convolutional networks for inferring gene interaction from spatial transcriptomics data. Genome Biol. 2020;21(1):1–16.Article 

Google Scholar 
Cang Z, Nie Q. Inferring spatial and signaling relationships between cells from single cell transcriptomic data. Nat Commun. 2020;11(1):2084.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Arnol D, Schapiro D, Bodenmiller B, Saez-Rodriguez J, Stegle O. Modeling cell-cell interactions from spatial molecular data with spatial variance component analysis. Cell Rep. 2019;29(1):202–11.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Fischer DS, Schaar AC, Theis FJ. Modeling intercellular communication in tissues using spatial graphs of cells. Nat Biotechnol 2022;1–5.Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M, Meyer KB, Park J-E, Stephenson E, Polański K, Goncalves A, et al. Single-cell reconstruction of the early maternal-fetal interface in humans. Nature. 2018;563(7731):347–53.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Efremova M, Vento-Tormo M, Teichmann SA, Vento-Tormo R. Cellphonedb: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat Protoc. 2020;15(4):1484–506.Article 
CAS 
PubMed 

Google Scholar 
Garcia-Alonso L, Handfield L-F, Roberts K, Nikolakopoulou K, Fernando RC, Gardner L, Woodhams B, Arutyunyan A, Polanski K, Hoo R, et al. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro. Nat Genet. 2021;53(12):1698–711.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Verma A, Jena SG, Isakov DR, Aoki K, Toettcher JE, Engelhardt BE. A self-exciting point process to study multicellular spatial signaling patterns. Proc Natl Acad Sci. 2021;118(32):2026123118.Article 

Google Scholar 
Borjini N, Paouri E, Tognatta R, Akassoglou K, Davalos D. Imaging the dynamic interactions between immune cells and the neurovascular interface in the spinal cord. Exp Neurol. 2019;322: 113046.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Nava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, Li X, Arcos JMG, et al. Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell. 2020;181(4):800–17.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
GTEx Consortium: Genetic effects on gene expression across human tissues. Nature 550(7675);204–213.Haghighi M, Caicedo JC, Cimini BA, Carpenter AE, Singh S. High-dimensional gene expression and morphology profiles of cells across 28,000 genetic and chemical perturbations. Nat Methods. 2022;1–8.Stirling DR, Swain-Bowden MJ, Lucas AM, Carpenter AE, Cimini BA, Goodman A. Cell Profiler 4: improvements in speed, utility and usability. BMC Bioinf. 2021;22:1–11.Article 

Google Scholar 
Ramezani M, Bauman J, Singh A, Weisbart E, Yong J, Lozada ME, Way GP, Kavari SL, Diaz C, Haghighi M, et al. A genome-wide atlas of human cell morphology. bioRxiv, 2023;2023–08.Goodfellow I, Pouget-Abadie J, Mirza M, Xu B, Warde-Farley D, Ozair S, Courville A, Bengio Y. Generative adversarial networks. Commun ACM. 2020;63(11):139–44.Article 

Google Scholar 
Lee H, Welch JD. Morphnet predicts cell morphology from single-cell gene expression. bioRxiv, 2022;2022–10.Sivanandan S, Leitmann B, Lubeck E, Sultan MM, Stanitsas P, Ranu N, Ewer A, Mancuso JE, Phillips ZF, Kim A, et al. A pooled cell painting crispr screening platform enables de novo inference of gene function by self-supervised deep learning. bioRxiv, 2023;2023–08.McSwiggen DT, Liu H, Tan R, Agramunt Puig S, Akella LB, Berman R, Bretan M, Chen H, Darzacq X, Ford K, et al. High-throughput single molecule tracking identifies drug interactions and cellular mechanisms. bioRxiv, 2023;2023–01.Sun J, Ramos A, Chapman B, Johnnidis JB, Le L, Ho Y-J, Klein A, Hofmann O, Camargo FD. Clonal dynamics of native haematopoiesis. Nature. 2014;514(7522):322–7.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Fabre MA, de Almeida JG, Fiorillo E, Mitchell E, Damaskou A, Rak J, Orrù V, Marongiu M, Chapman MS, Vijayabaskar M, et al. The longitudinal dynamics and natural history of clonal haematopoiesis. Nature. 2022;606(7913):335–42.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Klein AM, Doupé DP, Jones PH, Simons BD. Kinetics of cell division in epidermal maintenance. Phys Rev E. 2007;76(2): 021910.Article 

Google Scholar 
Klein AM, Doupé DP, Jones PH, Simons BD. Mechanism of murine epidermal maintenance: Cell division and the voter model. Phys Rev E. 2008;77(3): 031907.Article 

Google Scholar 
Parigini C, Greulich P. Universality of clonal dynamics poses fundamental limits to identify stem cell self-renewal strategies. Elife. 2020;9:56532.Article 

Google Scholar 
Gudmundsdottir H, Wells AD, Turka LA. Dynamics and requirements of t cell clonal expansion in vivo at the single-cell level: effector function is linked to proliferative capacity. J Immunol. 1999;162(9):5212–23.Article 
CAS 
PubMed 

Google Scholar 
Gerrits A, Dykstra B, Kalmykowa OJ, Klauke K, Verovskaya E, Broekhuis MJ, de Haan G, Bystrykh LV. Cellular barcoding tool for clonal analysis in the hematopoietic system. Blood, J Am Soc Hematol. 2010;115(13):2610–8.CAS 

Google Scholar 
Nguyen LV, Pellacani D, Lefort S, Kannan N, Osako T, Makarem M, Cox CL, Kennedy W, Beer P, Carles A, et al. Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells. Nature. 2015;528(7581):267–71.Article 
CAS 
PubMed 

Google Scholar 
Spanjaard B, Hu B, Mitic N, Olivares-Chauvet P, Janjuha S, Ninov N, Junker JP. Simultaneous lineage tracing and cell-type identification using crispr-cas9-induced genetic scars. Nat Biotechnol. 2018;36(5):469–73.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ishiguro S, Ishida K, Sakata RC, Mori H, Takana M, King S, Bashth O, Ichiraku M, Masuyama N, Takimoto R, et al.: A multi-kingdom genetic barcoding system for precise target clone isolation. BioRxiv, 2023;2023–01.Koster MI, Roop DR. Mechanisms regulating epithelial stratification. Annu Rev Cell Dev Biol. 2007;23:93–113.Article 
CAS 
PubMed 

Google Scholar 
Colom B, Alcolea MP, Piedrafita G, Hall MW, Wabik A, Dentro SC, Fowler JC, Herms A, King C, Ong SH, et al. Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium. Nat Genet. 2020;52(6):604–14.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Colom B, Herms A, Hall M, Dentro S, King C, Sood R, Alcolea M, Piedrafita G, Fernandez-Antoran D, Ong S, et al. Mutant clones in normal epithelium outcompete and eliminate emerging tumours. Nature. 2021;598(7881):510–4.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Blanpain C, Fuchs E. Plasticity of epithelial stem cells in tissue regeneration. Science. 2014;344(6189):1242281.Article 
PubMed 
PubMed Central 

Google Scholar 
Ma Y, Zhou X. Spatially informed cell-type deconvolution for spatial transcriptomics. Nat Biotechnol. 2022;40(9):1349–59.Article 
CAS 
PubMed 

Google Scholar 
Ru B, Huang J, Zhang Y, Aldape K, Jiang P. Estimation of cell lineages in tumors from spatial transcriptomics data. Nat Commun. 2023;14(1):568.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Elyanow R, Zeira R, Land M, Raphael BJ. Starch: copy number and clone inference from spatial transcriptomics data. Phys Biol. 2021;18(3): 035001.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Shaffer SM, Dunagin MC, Torborg SR, Torre EA, Emert B, Krepler C, Beqiri M, Sproesser K, Brafford PA, Xiao M, et al. Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance. Nature. 2017;546(7658):431–5.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Reiter JG, Makohon-Moore AP, Gerold JM, Heyde A, Attiyeh MA, Kohutek ZA, Tokheim CJ, Brown A, DeBlasio RM, Niyazov J, et al. Minimal functional driver gene heterogeneity among untreated metastases. Science. 2018;361(6406):1033–7.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Elowitz MB, Levine AJ, Siggia ED, Swain PS. Stochastic gene expression in a single cell. Science. 2002;297(5584):1183–6.Article 
CAS 
PubMed 

Google Scholar 
Swain PS, Elowitz MB, Siggia ED. Intrinsic and extrinsic contributions to stochasticity in gene expression. Proc Natl Acad Sci. 2002;99(20):12795–800.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Townes FW, Engelhardt BE. Nonnegative spatial factorization applied to spatial genomics. Nat Methods. 2023;20(2):229–38.Article 
CAS 
PubMed 

Google Scholar 
Velten B, Braunger JM, Argelaguet R, Arnol D, Wirbel J, Bredikhin D, Zeller G, Stegle O. Identifying temporal and spatial patterns of variation from multimodal data using MEFISTO. Nat Methods. 2022;19(2):179–86.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Yeung T, Georges PC, Flanagan LA, Marg B, Ortiz M, Funaki M, Zahir N, Ming W, Weaver V, Janmey PA. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil Cytoskelet. 2005;60(1):24–34.Article 

Google Scholar 
Meng K, Wang J, Crawford L, Eloyan A. Randomness and statistical inference of shapes via the smooth Euler characteristic transform. arXiv preprint arXiv:2204.12699 2022;Lechler T, Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature. 2005;437(7056):275–80.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Moffitt JR, Hao J, Wang G, Chen KH, Babcock HP, Zhuang X. High-throughput single-cell gene-expression profiling with multiplexed error-robust fluorescence in situ hybridization. Proc Natl Acad Sci. 2016;113(39):11046–51.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Groiss S, Pabst D, Faber C, Meier A, Bogdoll A, Unger C, Nilges B, Strauss S, Föderl-Höbenreich E, Hardt M, et al. Highly resolved spatial transcriptomics for detection of rare events in cells. bioRxiv, 2021;2021–10.Torre E, Dueck H, Shaffer S, Gospocic J, Gupte R, Bonasio R, Kim J, Murray J, Raj A. Rare cell detection by single-cell rna sequencing as guided by single-molecule rna fish. Cell Syst. 2018;6(2):171–9.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Cable DM, Murray E, Shanmugam V, Zhang S, Zou LS, Diao M, Chen H, Macosko EZ, Irizarry RA, Chen F. Cell type-specific inference of differential expression in spatial transcriptomics. Nat Methods. 2022;19(9):1076–87.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Schürch CM, Bhate SS, Barlow GL, Phillips DJ, Noti L, Zlobec I, Chu P, Black S, Demeter J, McIlwain DR, et al. Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front. Cell. 2020;182(5):1341–59.Article 
PubMed 
PubMed Central 

Google Scholar 
Xu C, Jin X, Wei S, Wang P, Luo M, Xu Z, Yang W, Cai Y, Xiao L, Lin X, et al. Deepst: identifying spatial domains in spatial transcriptomics by deep learning. Nucleic Acids Res. 2022;50(22):131–131.Article 

Google Scholar 
Shi X, Zhu J, Long Y, Liang C. Identifying spatial domains of spatially resolved transcriptomics via multi-view graph convolutional networks. Brief Bioi 2023;278.Shang L, Zhou X. Spatially aware dimension reduction for spatial transcriptomics. Nat Commun. 2022;13(1):7203.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Theodoris CV, Xiao L, Chopra A, Chaffin MD, Al Sayed ZR, Hill MC, Mantineo H, Brydon EM, Zeng Z, Liu XS, et al. Transfer learning enables predictions in network biology. Nature. 2023;1–9.Verma A, Engelhardt BE. A robust nonlinear low-dimensional manifold for single cell rna-seq data. BMC Bioinf. 2020;21(1):1–15.Article 

Google Scholar 
Lopez R, Regier J, Cole MB, Jordan MI, Yosef N. Deep generative modeling for single-cell transcriptomics. Nat Methods. 2018;15(12):1053–8.Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 

Hot Topics

Related Articles