Highly multiplexed in situ protein imaging with signal amplification by Immuno-SABER
Open accessPreprint — published as 10.1038/s41587-019-0207-y
Abstract
Probing the molecular organization of tissues requires in situ analysis by microscopy. However current limitations in multiplexing, sensitivity, and throughput collectively constitute a major barrier for comprehensive single-cell profiling of proteins. Here, we report Immunostaining with Signal Amplification By Exchange Reaction (Immuno-SABER), a rapid, highly multiplexed signal amplification method that simultaneously tackles these key challenges. Immuno-SABER utilizes DNA-barcoded antibodies and provides a method for highly multiplexed signal amplification via modular orthogonal DNA concatemers generated by Primer Exchange Reaction. This approach offers the capability to preprogram and control the amplification level independently for multiple targets without in situ enzymatic reactions, and the intrinsic scalability to rapidly amplify and image a large number of protein targets. We validated our approach in diverse sample types including cultured cells, cryosections, FFPE sections, and whole mount tissues. We demonstrated independently tunable 5-180-fold amplification for multiple targets, covering the full signal range conventionally achieved by secondary antibodies to tyramide signal amplification, as well as simultaneous signal amplification for 10 different proteins using standard equipment and workflow. We further combined Immuno-SABER with Expansion Microscopy to enable rapid and highly multiplexed super-resolution tissue imaging. Overall, Immuno-SABER presents an effective and accessible platform for rapid, multiplexed imaging of proteins across scales with high sensitivity.
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Cites
Deep Residual Learning for Image Recognition
He, K., Zhang, X., Ren, S., & Sun, J. (2016) · 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR) · doi:10.1109/cvpr.2016.90 · Cited by 235,474 · see citing works
U-Net: Convolutional Networks for Biomedical Image Segmentation
Ronneberger, O., Fischer, P., & Brox, T. (2015) · Lecture notes in computer science · doi:10.1007/978-3-319-24574-4_28 · Cited by 99,404 · see citing works
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Tissue-based map of the human proteome
Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., et al. (2015) · Science · doi:10.1126/science.1260419 · Cited by 15,286 · see citing works
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
CellProfiler: image analysis software for identifying and quantifying cell phenotypes
Carpenter, A. E., Jones, T. R., Lamprecht, M. R., Clarke, C., Kang, I. H., Friman, O., Guertin, D. A., Chang, J. H., Lindquist, R. A., Moffat, J., et al. (2006) · Genome biology · doi:10.1186/gb-2006-7-10-r100 · Cited by 5,172 · see citing works
Simultaneous epitope and transcriptome measurement in single cells
Stoeckius, M., Hafemeister, C., Stephenson, W., Houck-Loomis, B., Chattopadhyay, P. K., Swerdlow, H., Satija, R., & Smibert, P. (2017) · Nature Methods · doi:10.1038/nmeth.4380 · Cited by 3,098 · see citing works
Spatially resolved, highly multiplexed RNA profiling in single cells
Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S., & Zhuang, X. (2015) · Science · doi:10.1126/science.aaa6090 · Cited by 2,969 · see citing works
(2012) · doi:10.1016/j.jmoldx.2011.08.002 · Cited by 2,567 · see citing works
Regev, A., Teichmann, S. A., Lander, E. S., Amit, I., Benoist, C., Birney, E., Bodenmiller, B., Campbell, P., Carninci, P., Clatworthy, M., et al. (2017) · eLife · doi:10.7554/elife.27041 · Cited by 2,232 · see citing works
Triggered amplification by hybridization chain reaction
Dirks, R. M., & Pierce, N. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407024101 · Cited by 2,077 · see citing works
Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry
Giesen, C., Wang, H. A. O., Schapiro, D., Zivanovic, N., Jacobs, A., Hattendorf, B., Schüffler, P. J., Grolimund, D., Buhmann, J. M., Brandt, S., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2869 · Cited by 1,951 · see citing works
NUPACK: Analysis and design of nucleic acid systems
Zadeh, J. N., Steenberg, C. D., Bois, J. S., Wolfe, B. R., Pierce, M. B., Khan, A. R., Dirks, R. M., & Pierce, N. A. (2011) · Journal of Computational Chemistry · doi:10.1002/jcc.21596 · Cited by 1,670 · see citing works
Three-dimensional intact-tissue sequencing of single-cell transcriptional states
Wang, X., Allen, W. E., Wright, M. A., Sylwestrak, E. L., Samusik, N., Vesuna, S., Evans, K., Liu, C., Ramakrishnan, C., Liu, J., et al. (2018) · Science · doi:10.1126/science.aat5691 · Cited by 1,620 · see citing works
Amir, E.-A. D., Davis, K. L., Tadmor, M. D., Simonds, E. F., Levine, J. H., Bendall, S. C., Shenfeld, D. K., Krishnaswamy, S., Nolan, G. P., & Pe'er, D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2594 · Cited by 1,550 · see citing works
Chen, F., Tillberg, P. W., & Boyden, E. S. (2015) · Science · doi:10.1126/science.1260088 · Cited by 1,531 · see citing works
Self-citationDeep profiling of mouse splenic architecture with CODEX multiplexed imaging
Goltsev, Y., Samusik, N., Kennedy-Darling, J., Bhate, S., Hale, M., Vazquez, G., Black, S., & Nolan, G. P. (2018) · Cell · doi:10.1016/j.cell.2018.07.010 · Cited by 1,501 · see citing works
Choi, H. M. T., Schwarzkopf, M., Fornace, M. E., Acharya, A., Artavanis, G., Stegmaier, J., Cunha, A., & Pierce, N. A. (2018) · Development · doi:10.1242/dev.165753 · Cited by 1,495 · see citing works
Regev, A., Teichmann, S. A., Lander, E. S., Amit, I., Benoist, C. O., Birney, E., Bodenmiller, B., & al, E. (2017) · Zurich Open Repository and Archive (University of Zurich) · doi:10.5167/uzh-162597 · Cited by 1,457 · see citing works
Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT
Jungmann, R., Avendaño, M. S., Woehrstein, J. B., Dai, M., Shih, W. M., & Yin, P. (2014) · Nature Methods · doi:10.1038/nmeth.2835 · Cited by 1,137 · see citing works
Self-citationMultiplexed ion beam imaging of human breast tumors
Angelo, M., Bendall, S. C., Finck, R., Hale, M. B., Hitzman, C., Borowsky, A. D., Levenson, R. M., Lowe, J. B., Liu, S. D., Zhao, S., et al. (2014) · Nature Medicine · doi:10.1038/nm.3488 · Cited by 1,108 · see citing works
Highly Multiplexed Subcellular RNA Sequencing in Situ
Lee, J. H., Daugharthy, E. R., Scheiman, J., Kalhor, R., Yang, J. L., Ferrante, T. C., Terry, R., Jeanty, S. S. F., Li, C., Amamoto, R., et al. (2014) · Science · doi:10.1126/science.1250212 · Cited by 973 · see citing works
Self-citationBendall, S. C., Davis, K. L., Amir, E.-A. D., Tadmor, M. D., Simonds, E. F., Chen, T. J., Shenfeld, D. K., Nolan, G. P., & Pe’er, D. (2014) · Cell · doi:10.1016/j.cell.2014.04.005 · Cited by 906 · see citing works
The quantitative proteome of a human cell line
Beck, M., Schmidt, A., Malmstroem, J., Claassen, M., Ori, A., Szymborska, A., Herzog, F., Rinner, O., Ellenberg, J., & Aebersold, R. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.82 · Cited by 816 · see citing works
Stack, E. C., Wang, C., Roman, K., & Hoyt, C. C. (2014) · Methods · doi:10.1016/j.ymeth.2014.08.016 · Cited by 779 · see citing works
Catalyzed reporter deposition, a novel method of signal amplification application to immunoassays
Bobrow, M. N., Harris, T. D., Shaughnessy, K. J., & Litt, G. J. (1989) · Journal of Immunological Methods · doi:10.1016/0022-1759(89)90104-x · Cited by 774 · see citing works
Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue
Gerdes, M. J., Sevinsky, C. J., Sood, A., Adak, S., Bello, M. O., Bordwell, A., Can, A. B., Corwin, A. D., Dinn, S. R., Filkins, R. J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300136110 · Cited by 733 · see citing works
Programmable in situ amplification for multiplexed imaging of mRNA expression
Choi, H. M. T., Chang, J. Y., Trinh, L. A., Padilla, J. E., Fraser, S. E., & Pierce, N. A. (2010) · Nature Biotechnology · doi:10.1038/nbt.1692 · Cited by 720 · see citing works
Superresolution Imaging of Chemical Synapses in the Brain
Dani, A., Huang, B., Bergan, J. F., Dulac, C. G., & Zhuang, X. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.021 · Cited by 718 · see citing works
Shah, S., Lubeck, E., Zhou, W., & Cai, L. (2016) · Neuron · doi:10.1016/j.neuron.2016.10.001 · Cited by 671 · see citing works
OMERO: flexible, model-driven data management for experimental biology
Allan, C., Burel, J.-M., Moore, J., Blackburn, C., Linkert, M., Loynton, S., MacDonald, D., Moore, W. J., Neves, C., Patterson, A., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1896 · Cited by 653 · see citing works
histoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data
Schapiro, D., Jackson, H. W., Raghuraman, S., Fischer, J. R., Zanotelli, V. R., Schulz, D., Giesen, C., Catena, R., Varga, Z., & Bodenmiller, B. (2017) · Nature Methods · doi:10.1038/nmeth.4391 · Cited by 643 · see citing works
Next-Generation in Situ Hybridization Chain Reaction: Higher Gain, Lower Cost, Greater Durability
Choi, H. M. T., Beck, V. A., & Pierce, N. A. (2014) · ACS Nano · doi:10.1021/nn405717p · Cited by 634 · see citing works
Lin, J.-R., Izar, B., Wang, S., Yapp, C., Mei, S.-L., Shah, P., Santagata, S., & Sorger, P. (2018) · eLife · doi:10.7554/elife.31657 · Cited by 631 · see citing works
Self-citationSchweitzer, B. I., Wiltshire, S., Lambert, J., O'Malley, S. M., Kukanskis, K. A., Zhu, Z., Kingsmore, S. F., Lizardi, P. M., & Ward, D. C. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.170237197 · Cited by 597 · see citing works
The human body at cellular resolution: the NIH Human Biomolecular Atlas Program
HuBMAP Consortium, Writing Group, Snyder, M. P., Lin, S., Posgai, A., Atkinson, M., Regev, A., Rood, J., Rozenblatt-Rosen, O., Gaffney, L., et al. (2019) · Nature · doi:10.1038/s41586-019-1629-x · Cited by 595 · see citing works
Self-citationHighly multiplexed imaging of single cells using a high-throughput cyclic immunofluorescence method
Lin, J., Fallahi‐Sichani, M., & Sorger, P. K. (2015) · Nature Communications · doi:10.1038/ncomms9390 · Cited by 562 · see citing works
Moffitt, J. R., Hao, J., Wang, G., Chen, K. H., Babcock, H. P., & Zhuang, X. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612826113 · Cited by 557 · see citing works
Super-multiplex vibrational imaging
Wei, L., Chen, Z., Shi, L., Long, R., Anzalone, A. V., Zhang, L., Hu, F., Yuste, R., Cornish, V. W., & Min, W. (2017) · Nature · doi:10.1038/nature22051 · Cited by 514 · see citing works
Multiplexed protein maps link subcellular organization to cellular states
Gut, G., Herrmann, M. D., & Pelkmans, L. (2018) · Science · doi:10.1126/science.aar7042 · Cited by 510 · see citing works
Ku, T., Swaney, J., Park, J. Y., Albanese, A., Murray, E. M., Cho, J. H., Park, Y.-G., Mangena, V., Chen, J., & Chung, K. (2016) · Nature Biotechnology · doi:10.1038/nbt.3641 · Cited by 466 · see citing works
SABER amplifies FISH: enhanced multiplexed imaging of RNA and DNA in cells and tissues
Kishi, J. Y., Lapan, S. W., Beliveau, B. J., West, E. R., Zhu, A., Sasaki, H. M., Saka, S. K., Wang, Y., Cepko, C. L., & Yin, P. (2019) · Nature Methods · doi:10.1038/s41592-019-0404-0 · Cited by 440 · see citing works
Self-citationMapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler
Chen, Y., Zhang, Y., Wang, Y., Zhang, L., Brinkman, E. K., Adam, S. A., Goldman, R. D., van Steensel, B., Ma, J., & Belmont, A. S. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201807108 · Cited by 435 · see citing works
Self-citationNanoscale imaging of RNA with expansion microscopy
Chen, F., Wassie, A. T., Coté, A., Sinha, A., Alon, S., Asano, S. M., Daugharthy, E. R., Chang, J., Marblestone, A. H., Church, G. M., et al. (2016) · Nature Methods · doi:10.1038/nmeth.3899 · Cited by 411 · see citing works
Self-citationA partition function algorithm for nucleic acid secondary structure including pseudoknots
Dirks, R. M., & Pierce, N. (2003) · Journal of Computational Chemistry · doi:10.1002/jcc.10296 · Cited by 403 · see citing works
Iterative expansion microscopy
Chang, J., Chen, F., Yoon, Y., Jung, E. E., Babcock, H. P., Kang, J. S., Asano, S. M., Suk, H., Pak, N., Tillberg, P. W., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4261 · Cited by 390 · see citing works
Self-citationDefining the transcriptome and proteome in three functionally different human cell lines
Lundberg, E., Fagerberg, L., Klevebring, D., Matic, I., Geiger, T., Cox, J., Älgenäs, C., Lundeberg, J., Mann, M., & Uhlen, M. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.106 · Cited by 373 · see citing works
Programmable autonomous synthesis of single-stranded DNA
Kishi, J. Y., Schaus, T. E., Gopalkrishnan, N., Xuan, F., & Yin, P. (2017) · Nature Chemistry · doi:10.1038/nchem.2872 · Cited by 321 · see citing works
Self-citationSchulz, D., Zanotelli, V. R., Fischer, J. R., Schapiro, D., Engler, S., Lun, X., Jackson, H. W., & Bodenmiller, B. (2017) · Cell Systems · doi:10.1016/j.cels.2017.12.001 · Cited by 279 · see citing works
Image-based transcriptomics in thousands of single human cells at single-molecule resolution
Battich, N., Stoeger, T., & Pelkmans, L. (2013) · Nature Methods · doi:10.1038/nmeth.2657 · Cited by 269 · see citing works
Super-Resolution Microscopy: From Single Molecules to Supramolecular Assemblies
Sydor, A. M., Czymmek, K. J., Puchner, E. M., & Mennella, V. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.004 · Cited by 251 · see citing works
Correction: Corrigendum: Global quantification of mammalian gene expression control
Schwanhäußer, B., Busse, D., Li, N., Dittmar, G. A. G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2013) · Nature · doi:10.1038/nature11848 · Cited by 249 · see citing works
Morphology and immunology of the human palatine tonsil
Nave, H., Gebert, A., & Pabst, R. (2001) · Anatomy and Embryology · doi:10.1007/s004290100210 · Cited by 248 · see citing works
X10 expansion microscopy enables 25‐nm resolution on conventional microscopes
Truckenbrodt, S., Maidorn, M., Crzan, D., Wildhagen, H., Kabatas, S., & Rizzoli, S. O. (2018) · EMBO Reports · doi:10.15252/embr.201845836 · Cited by 242 · see citing works
Pachl, C. A., Todd, J. A., Kern, D. G., Sheridan, P. J., Fong, S.-J., Stempien, M. M., Hoo, B., Besemer, D. J., Yeghiazarian, T., Irvine, B. D., et al. (1995) · Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology · doi:10.1097/00042560-199504120-00003 · Cited by 232 · see citing works
The challenge of the proteome dynamic range and its implications for in‐depth proteomics
Zubarev, R. A. (2013) · PROTEOMICS · doi:10.1002/pmic.201200451 · Cited by 230 · see citing works
Shah, S., Lubeck, E., Schwarzkopf, M., He, T.-F., Greenbaum, A., Sohn, C. H., Lignell, A., Choi, H. M. T., Gradinaru, V., Pierce, N. A., et al. (2016) · Development · doi:10.1242/dev.138560 · Cited by 210 · see citing works
DNA-barcoded labeling probes for highly multiplexed Exchange-PAINT imaging
Agasti, S. S., Wang, Y., Schueder, F., Sukumar, A., Jungmann, R., & Yin, P. (2017) · Chemical Science · doi:10.1039/c6sc05420j · Cited by 200 · see citing works
Self-citationSingle-copy Gene Detection Using Branched DNA (bDNA) In Situ Hybridization
Player, A. N., Shen, L., Kenny, D. A., Antao, V., & Kolberg, J. A. (2001) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540104900507 · Cited by 196 · see citing works
DNA-Sequence-Encoded Rolling Circle Amplicon for Single-Cell RNA Imaging
Deng, R., Zhang, K., Wang, L., Ren, X., Sun, Y., & Li, J. (2018) · Chem · doi:10.1016/j.chempr.2018.03.003 · Cited by 185 · see citing works
Amplification Methods to Increase the Sensitivity of In Situ Hybridization: Play CARD(S)
Speel, E. M., Hopman, A. H. N., & Komminoth, P. (1999) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549904700302 · Cited by 184 · see citing works
An algorithm for computing nucleic acid base‐pairing probabilities including pseudoknots
Dirks, R. M., & Pierce, N. A. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20057 · Cited by 171 · see citing works
The use of catalyzed reporter deposition as a means of signal amplification in a variety of formats
Bobrow, M. N., Litt, G. J., Shaughnessy, K. J., Mayer, P., & Conlon, J. S. (1992) · Journal of Immunological Methods · doi:10.1016/0022-1759(92)90073-3 · Cited by 159 · see citing works
Multiplexed Intact-Tissue Transcriptional Analysis at Cellular Resolution
Sylwestrak, E., Rajasethupathy, P., Wright, M. A., Jaffe, A., & Deisseroth, K. A. (2016) · Cell · doi:10.1016/j.cell.2016.01.038 · Cited by 151 · see citing works
Rapid Sequential in Situ Multiplexing with DNA Exchange Imaging in Neuronal Cells and Tissues
Wang, Y., Woehrstein, J. B., Donoghue, N. D., Dai, M., Avendaño, M. S., Schackmann, R. C. J., Zoeller, J. J., Wang, S. S. H., Tillberg, P. W., Park, D., et al. (2017) · Nano Letters · doi:10.1021/acs.nanolett.7b02716 · Cited by 151 · see citing works
Self-citationKern, D., Collins, M., Fultz, T. J., Detmer, J. J., Hamren, S., Peterkin, J. J., Sheridan, P., Urdea, M. S., White, R., Yeghiazarian, T., et al. (1996) · Journal of Clinical Microbiology · doi:10.1128/jcm.34.12.3196-3202.1996 · Cited by 151 · see citing works
ClampFISH detects individual nucleic acid molecules using click chemistry–based amplification
Rouhanifard, S. H., Mellis, I. A., Dunagin, M. C., Bayatpour, S., Jiang, C., Dardani, I. P., Symmons, O., Emert, B. L., Torre, E. A., Coté, A., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4286 · Cited by 147 · see citing works
A hybridization-chain-reaction-based method for amplifying immunosignals
Lin, R., Feng, Q., Li, P., Zhou, P., Wang, R., Liu, Z., Wang, Z., Qi, X., Tang, N., Shao, F., et al. (2018) · Nature Methods · doi:10.1038/nmeth.4611 · Cited by 125 · see citing works
Slijkerman, R. W. N., Song, F., Astuti, G., Huynen, M. A., van Wijk, E., Stieger, K., & Collin, R. W. J. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.04.004 · Cited by 114 · see citing works
Bernstein, H., Baumann, B., Dános, P., Diekmann, S., Bogerts, B., Gundelfinger, E. D., & Braunewell, K. (1999) · Journal of Neurocytology · doi:10.1023/a:1007056731551 · Cited by 113 · see citing works
Immunohistochemistry and mass spectrometry for highly multiplexed cellular molecular imaging
Levenson, R. M., Borowsky, A. D., & Angelo, M. R. (2015) · Laboratory Investigation · doi:10.1038/labinvest.2015.2 · Cited by 112 · see citing works
Automated cell-type classification in intact tissues by single-cell molecular profiling
Nagendran, M., Riordan, D. P., Harbury, P. B., & Desai, T. (2018) · eLife · doi:10.7554/elife.30510 · Cited by 105 · see citing works
Universal Super‐Resolution Multiplexing by DNA Exchange
Schueder, F., Strauss, M. T., Hörl, D., Schnitzbauer, J., Schlichthaerle, T., Strauss, S., Yin, P., Harz, H., Leonhardt, H., & Jungmann, R. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201611729 · Cited by 95 · see citing works
Self-citationTakada, S., & Engleman, E. G. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.139.10.3231 · Cited by 82 · see citing works
Multidimensional quantitative analysis of mRNA expression within intact vertebrate embryos
Trivedi, V., Choi, H. M. T., Fraser, S. E., & Pierce, N. A. (2018) · Development · doi:10.1242/dev.156869 · Cited by 62 · see citing works
Strength in numbers: quantitative single‐molecule RNA detection assays
Gáspár, I., & Ephrussi, A. (2015) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.170 · Cited by 58 · see citing works
Tyramide signal amplification for analysis of kinase activity by intracellular flow cytometry
Clutter, M. R., Heffner, G. C., Krutzik, P. O., Sachen, K. L., & Nolan, G. P. (2010) · Cytometry Part A · doi:10.1002/cyto.a.20970 · Cited by 49 · see citing works
Yarilin, D. A., Xu, K., Turkekul, M., Fan, N., Romin, Y., Fijisawa, S., Barlas, A., & Manova-Todorova, K. O. (2015) · Scientific Reports · doi:10.1038/srep09534 · Cited by 43 · see citing works
Multiplexed tissue biomarker imaging
Stack, E. C., Foukas, P. G., & Lee, P. P. (2016) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0115-3 · Cited by 36 · see citing works
Miyata, S., Funatsu, N., Matsunaga, W., Kiyohara, T., Sokawa, Y., & Maékawa, S. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000814)424:1 · Cited by 35 · see citing works
Wang, Y., Zeng, Y., Saka, S. K., Xie, W., Goldaracena, I., Kohman, R. E., Yin, P., & Church, G. M. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/274456 · Cited by 19 · see citing works
Self-citationBüki, A., Walker, S. A., Stone, J. R., & Povlishock, J. T. (2000) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540004800116 · Cited by 19 · see citing works
Garrigues, H. J., Rubinchikova, Y. E., & Rose, T. M. (2014) · Virology · doi:10.1016/j.virol.2014.01.006 · Cited by 12 · see citing works
Guo, S.-M., Veneziano, R., Gordonov, S., Li, L., Park, D., Kulesa, A. B., Blainey, P. C., Cottrell, J. R., Boyden, E. S., & Bathe, M. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/111625 · Cited by 7 · see citing works
Self-citationA Hybridization Chain Reaction-based Method for Amplifying Immunosignals
Lin, R., Lin, R., Feng, Q., Li, P., Zhou, P., Wang, R., Liu, Z., Wang, Z., Qi, X., Tang, N., et al. (2018) · Protocol Exchange · doi:10.1038/protex.2018.014 · Cited by 3 · see citing works
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Eleven grand challenges in single-cell data science
Lähnemann, D., Köster, J., Szczurek, E., McCarthy, D. J., Hicks, S. C., Robinson, M. D., Vallejos, C. A., Campbell, K. R., Beerenwinkel, N., Mahfouz, A., et al. (2020) · Genome Biology · doi:10.1186/s13059-020-1926-6 · Cited by 1,327 · see citing works
Methods and applications for single-cell and spatial multi-omics
Vandereyken, K., Sifrim, A., Thienpont, B., & Voet, T. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00580-2 · Cited by 1,244 · see citing works
Schürch, C. M., Bhate, S. S., Barlow, G. L., Phillips, D. J., Noti, L., Zlobec, I., Chu, P., Black, S., Demeter, J., McIlwain, D. R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.005 · Cited by 1,058 · see citing works
CODEX multiplexed tissue imaging with DNA-conjugated antibodies
Black, S. A., Phillips, D. J., Hickey, J. W., Kennedy‐Darling, J., Venkataraaman, V. G., Samusik, N., Goltsev, Y., Schürch, C. M., & Nolan, G. P. (2021) · Nature Protocols · doi:10.1038/s41596-021-00556-8 · Cited by 668 · see citing works
Spatial omics and multiplexed imaging to explore cancer biology
Lewis, S. M., Asselin-Labat, M.-L., Nguyen, Q. H., Berthelet, J., Tan, X., Wimmer, V. C., Mérino, D., Rogers, K. L., & Naik, S. H. (2021) · Nature Methods · doi:10.1038/s41592-021-01203-6 · Cited by 609 · see citing works
The human body at cellular resolution: the NIH Human Biomolecular Atlas Program
HuBMAP Consortium, Writing Group, Snyder, M. P., Lin, S., Posgai, A., Atkinson, M., Regev, A., Rood, J., Rozenblatt-Rosen, O., Gaffney, L., et al. (2019) · Nature · doi:10.1038/s41586-019-1629-x · Cited by 595 · see citing works
Self-citationSpatial profiling technologies illuminate the tumor microenvironment
Elhanani, O., Ben-Uri, R., & Keren, L. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.01.010 · Cited by 525 · see citing works
SABER amplifies FISH: enhanced multiplexed imaging of RNA and DNA in cells and tissues
Kishi, J. Y., Lapan, S. W., Beliveau, B. J., West, E. R., Zhu, A., Sasaki, H. M., Saka, S. K., Wang, Y., Cepko, C. L., & Yin, P. (2019) · Nature Methods · doi:10.1038/s41592-019-0404-0 · Cited by 440 · see citing works
Self-citationMIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure
Keren, L., Bosse, M. M., Thompson, S., Risom, T., Vijayaragavan, K., McCaffrey, E., Marquez, D. M., Angoshtari, R., Greenwald, N. F., Fienberg, H. G., et al. (2019) · Science Advances · doi:10.1126/sciadv.aax5851 · Cited by 441 · see citing works
The emerging landscape of spatial profiling technologies
Moffitt, J. R., Lundberg, E., & Heyn, H. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00515-3 · Cited by 419 · see citing works
Hickey, J. W., Neumann, E. K., Radtke, A. J., Camarillo, J. M., Beuschel, R. T., Albanese, A., McDonough, E., Hatler, J. M., Wiblin, A. E., Fisher, J., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01316-y · Cited by 317 · see citing works
Self-citationSpatial and temporal scales of dopamine transmission
Liu, C., Goel, P., & Kaeser, P. S. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00455-7 · Cited by 302 · see citing works
Self-citationAn end-to-end workflow for multiplexed image processing and analysis
Windhager, J., Zanotelli, V. R., Schulz, D., Meyer, L., Daniel, M., Bodenmiller, B., & Eling, N. (2023) · Nature Protocols · doi:10.1038/s41596-023-00881-0 · Cited by 290 · see citing works
Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer
Lin, J., Wang, S., Coy, S., Chen, Y., Yapp, C., Tyler, M., Nariya, M. K., Heiser, C. N., Lau, K. S., Santagata, S., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.028 · Cited by 284 · see citing works
Self-citationPresynaptic calcium channels: specialized control of synaptic neurotransmitter release
DOLPHIN, A. C., & Lee, A. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0278-2 · Cited by 284 · see citing works
Advances in spatial transcriptomic data analysisPreprint
Dries, R., Chen, J. G., Rossi, N. D., Khan, M. M., Sistig, A., & Yuan, G. (2021) · Genome Research · doi:10.1101/gr.275224.121 · Cited by 236 · see citing works
MCMICRO: a scalable, modular image-processing pipeline for multiplexed tissue imaging
Schapiro, D., Sokolov, A., Yapp, C., Chen, Y., Muhlich, J. L., Hess, J. M., Creason, A., Nirmal, A. J., Baker, G. J., Nariya, M. K., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01308-y · Cited by 229 · see citing works
Self-citationStoltzfus, C. R., Filipek, J., Gern, B. H., Olin, B. E., Leal, J. M., Wu, Y., Lyons‐Cohen, M. R., Huang, J. Y., Paz-Stoltzfus, C. L., Plumlee, C. R., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107523 · Cited by 241 · see citing works
Spatiotemporal omics for biology and medicine
Liu, L., Chen, A., Li, Y., Mulder, J., Heyn, H., & Xu, X. (2024) · Cell · doi:10.1016/j.cell.2024.07.040 · Cited by 238 · see citing works
Single-cell analysis targeting the proteome
Labib, M., & Kelley, S. O. (2020) · Nature Reviews Chemistry · doi:10.1038/s41570-020-0162-7 · Cited by 233 · see citing works
Li, X., Li, X., Li, D., Zhao, M., Wu, H., Shen, B., Liu, P., & Ding, S. (2020) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2020.112554 · Cited by 218 · see citing works
Spatial biology of cancer evolution
Seferbekova, Z., Lomakin, A., Yates, L. R., & Gerstung, M. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00553-x · Cited by 208 · see citing works
Light microscopy of proteins in their ultrastructural context
M’Saad, O., & Bewersdorf, J. (2020) · Nature Communications · doi:10.1038/s41467-020-17523-8 · Cited by 206 · see citing works
Spatial multi-omics analyses of the tumor immune microenvironment
Hsieh, W.-C., Budiarto, B. R., Wang, Y., Lin, C., Gwo, M.-C., So, D. K., Tzeng, Y.-S., & Chen, S.-Y. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00879-y · Cited by 215 · see citing works
Self-citationAkhoundova, D., & Rubin, M. A. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.08.011 · Cited by 188 · see citing works
Decoding the tumor microenvironment with spatial technologies
Walsh, L. A., & Quail, D. F. (2023) · Nature Immunology · doi:10.1038/s41590-023-01678-9 · Cited by 184 · see citing works
Prospects and challenges of dynamic DNA nanostructures in biomedical applications
Tian, T., Li, Y., & Lin, Y. (2022) · Bone Research · doi:10.1038/s41413-022-00212-1 · Cited by 171 · see citing works
Magnify is a universal molecular anchoring strategy for expansion microscopy
Klimas, A., Gallagher, B. R., Wijesekara, P., Fekir, S., DiBernardo, E. F., Cheng, Z., Stolz, D. B., Cambi, F., Watkins, S. C., Brody, S. L., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01546-1 · Cited by 150 · see citing works
Joint single-cell measurements of nuclear proteins and RNA in vivo
Chung, H., Parkhurst, C. N., Magee, E. M., Phillips, D., Habibi, E., Chen, F., Yeung, B. Z., Waldman, J., Artis, D., & Regev, A. (2021) · Nature Methods · doi:10.1038/s41592-021-01278-1 · Cited by 144 · see citing works
Radtke, A. J., Chu, C. J., Yaniv, Z., Li, Y., Marr, J., Beuschel, R. T., Ichise, H., Gola, A., Kabát, J., Lowekamp, B., et al. (2022) · Nature Protocols · doi:10.1038/s41596-021-00644-9 · Cited by 144 · see citing works
Strategies for Accurate Cell Type Identification in CODEX Multiplexed Imaging Data
Hickey, J. W., Tan, Y., Nolan, G. P., & Goltsev, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.727626 · Cited by 137 · see citing works
Spatial proteomics in three-dimensional intact specimens
Bhatia, H. S., Brunner, A.-D., Öztürk, F., Kapoor, S., Rong, Z., Mai, H., Thielert, M., Ali, M., Al-Maskari, R., Paetzold, J. C., et al. (2022) · Cell · doi:10.1016/j.cell.2022.11.021 · Cited by 129 · see citing works
Fully automated sequential immunofluorescence (seqIF) for hyperplex spatial proteomics
Rivest, F., Eroglu, D., Pelz, B., Kowal, J., Kehren, A., Navikas, V., Procopio, M. G., Bordignon, P., Pérès, E., Ammann, M., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-43435-w · Cited by 123 · see citing works
Schwarzkopf, M., Liu, M. C., Schulte, S. J., Ives, R., Husain, N., Choi, H. M. T., & Pierce, N. A. (2021) · Development · doi:10.1242/dev.199847 · Cited by 118 · see citing works
Super-resolving Microscopy in Neuroscience
Werner, C. D., Sauer, M., & Geis, C. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01174 · Cited by 111 · see citing works
Ko, J., Wilkovitsch, M., Oh, J., Köhler, R. H., Bolli, E., Pittet, M. J., Vinegoni, C., Sykes, D. B., Mikula, H., Weissleder, R., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01339-6 · Cited by 111 · see citing works
Highly-multiplexed volumetric mapping with Raman dye imaging and tissue clearing
Shi, L., Wei, M., Miao, Y., Qian, N., Shi, L., Singer, R. A., Benninger, R. K. P., & Min, W. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-01041-z · Cited by 110 · see citing works
Seo, J., Sim, Y., Kim, J., Kim, H., Cho, I., Nam, H., Yoon, Y., & Chang, J. (2022) · Nature Communications · doi:10.1038/s41467-022-30168-z · Cited by 110 · see citing works
Label-retention expansion microscopy
Shi, X., Li, Q., Dai, Z., Tran, A. A., Feng, S., Ramirez, A. D., Lin, Z., Wang, X., Chow, T. T., Chen, J., et al. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202105067 · Cited by 108 · see citing works
Spatial multi-omics: novel tools to study the complexity of cardiovascular diseases
Kießling, P., & Kuppe, C. (2024) · Genome Medicine · doi:10.1186/s13073-024-01282-y · Cited by 108 · see citing works
Lee, M. Y., Bedia, J. S., Bhate, S. S., Barlow, G. L., Phillips, D. J., Fantl, W. J., Nolan, G. P., & Schürch, C. M. (2022) · BMC Bioinformatics · doi:10.1186/s12859-022-04570-9 · Cited by 107 · see citing works
Basic principles of hydrogel-based tissue transformation technologies and their applications
Choi, S. W., Guan, W., & Chung, K. (2021) · Cell · doi:10.1016/j.cell.2021.07.009 · Cited by 105 · see citing works
Highly multiplexed tissue imaging using repeated oligonucleotide exchange reaction
Kennedy‐Darling, J., Bhate, S. S., Hickey, J. W., Black, S., Barlow, G. L., Vazquez, G., Venkataraaman, V. G., Samusik, N., Goltsev, Y., Schürch, C. M., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202048891 · Cited by 104 · see citing works
Quantification of tumor heterogeneity: from data acquisition to metric generation
Kashyap, A., Rapsomaniki, M., Barros, V., Khartchenko, A. F., Martinelli, A. L., Foncubierta–Rodríguez, A., Gabrani, M., Rosen‐Zvi, M., & Kaigala, G. V. (2021) · Trends in biotechnology · doi:10.1016/j.tibtech.2021.11.006 · Cited by 104 · see citing works
Deep-tissue transcriptomics and subcellular imaging at high spatial resolution
Gandin, V., Kim, J., Yang, L.-Z., Lian, Y., Kawase, T., Hu, A., Rokicki, K., Fleishman, G. M., Tillberg, P. W., Aguilera-Castrejon, A., et al. (2025) · Science · doi:10.1126/science.adq2084 · Cited by 100 · see citing works
Ko, J., Wang, Y., Carlson, J., Marquard, A. N., Gungabeesoon, J., Charest, A., Weitz, D. A., Pittet, M. J., & Weissleder, R. (2020) · Advanced Biosystems · doi:10.1002/adbi.201900307 · Cited by 97 · see citing works
Self-citationCoy, S., Wang, S., Stopka, S. A., Lin, J., Yapp, C., Ritch, C. C., Salhi, L., Baker, G. J., Rashid, R., Baquer, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32430-w · Cited by 98 · see citing works
Self-citationMultiplex protein imaging in tumour biology
de Souza, N., Zhao, S., & Bodenmiller, B. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-023-00657-4 · Cited by 93 · see citing works
Jiang, S., Chan, C. N., Clavé, X. R., Chen, H. M., Bai, Y., Zhu, B., McCaffrey, E., Greenwald, N. F., Liu, C. C., Barlow, G. L., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.03.020 · Cited by 94 · see citing works
Shun, H., Zhang, L., Su, Y., Liang, X., Yang, J., Luo, Q., & Luo, H. (2024) · Science Advances · doi:10.1126/sciadv.abm3088 · Cited by 94 · see citing works
Multiplex Immunofluorescence: A Powerful Tool in Cancer Immunotherapy
Sheng, W., Zhang, C., Mohiuddin, T. M., Al-Rawe, M., Zeppernick, F. A., Falcone, F. H., Meinhold-Heerlein, I. M., & Hussain, A. F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043086 · Cited by 93 · see citing works
CellSighter: a neural network to classify cells in highly multiplexed images
Amitay, Y., Bussi, Y., Feinstein, B., Bagon, S., Milo, I., & Keren, L. (2023) · Nature Communications · doi:10.1038/s41467-023-40066-7 · Cited by 93 · see citing works
Allam, M., Cai, S., & Coskun, A. F. (2020) · npj Precision Oncology · doi:10.1038/s41698-020-0114-1 · Cited by 91 · see citing works
Tissue schematics map the specialization of immune tissue motifs and their appropriation by tumors
Bhate, S. S., Barlow, G. L., Schürch, C. M., & Nolan, G. P. (2021) · Cell Systems · doi:10.1016/j.cels.2021.09.012 · Cited by 87 · see citing works
Robust phenotyping of highly multiplexed tissue imaging data using pixel-level clustering
Liu, C. C., Greenwald, N. F., Kong, A., McCaffrey, E., Leow, K. X., Mrdjen, D., Cannon, B. J., Rumberger, J. L., Varra, S. R., & Angelo, M. (2023) · Nature Communications · doi:10.1038/s41467-023-40068-5 · Cited by 81 · see citing works
Spatially resolved transcriptomics and its applications in cancer
Maniatis, S., Petrescu, J., & Phatnani, H. P. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.12.002 · Cited by 86 · see citing works
Revealing nanostructures in brain tissue via protein decrowding by iterative expansion microscopy
Sarkar, D., Kang, J., Wassie, A. T., Schroeder, M. E., Peng, Z., Tarr, T. B., Tang, A., Niederst, E. D., Young, J. Z., Su, H., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00912-3 · Cited by 86 · see citing works
Self-citationMITI minimum information guidelines for highly multiplexed tissue images
Schapiro, D., Yapp, C., Sokolov, A., Reynolds, S. M., Chen, Y.-A., Sudar, D., Xie, Y., Muhlich, J. L., Arias-Camison, R., Arena, S., et al. (2022) · Nature Methods · doi:10.1038/s41592-022-01415-4 · Cited by 84 · see citing works
Self-citationImmunology in the Era of Single-Cell Technologies
Efremova, M., Vento‐Tormo, R., Park, J.-E., Teichmann, S. A., & James, K. R. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090419-020340 · Cited by 77 · see citing works
In Situ Genetically Cascaded Amplification for Imaging RNA Subcellular Locations
Ren, K., Wu, R., Mudiyanselage, A. P. K. K. K., Yu, Q., Zhao, B., Xie, Y., Bagheri, Y., Tian, Q., & You, M. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b11748 · Cited by 77 · see citing works
cytomapper : an R/Bioconductor package for visualization of highly multiplexed imaging data
Eling, N., Damond, N., Hoch, T., & Bodenmiller, B. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa1061 · Cited by 76 · see citing works
Kishi, J. Y., Liu, N., West, E. R., Sheng, K., Jordanides, J. J., Serrata, M. P., Cepko, C. L., Saka, S. K., & Yin, P. (2022) · Nature Methods · doi:10.1038/s41592-022-01604-1 · Cited by 78 · see citing works
Self-citationHighly multiplexed, label-free proteoform imaging of tissues by individual ion mass spectrometry
Su, P., McGee, J., Durbin, K. R., Hollas, M., Yang, M.-X., Neumann, E. K., Allen, J. L., Drown, B. S., Butun, F., Greer, J. B., et al. (2022) · Science Advances · doi:10.1126/sciadv.abp9929 · Cited by 67 · see citing works
Engineered Tools to Study Intercellular Communication
Yang, B. A., Westerhof, T. M., Sabin, K., Merajver, S. D., & Aguilar, C. A. (2020) · Advanced Science · doi:10.1002/advs.202002825 · Cited by 73 · see citing works
Inde, Z., Croker, B. A., Yapp, C., Joshi, G. N., Spetz, J. K. E., Fraser, C. S., Qin, X., Xu, L., Deskin, B., Ghelfi, E., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf8609 · Cited by 72 · see citing works
Self-citationLiu, X., Mao, D., Song, Y., Zhu, L., Isak, A. N., Lu, C., Deng, G., Chen, F., Sun, F., Yang, Y. P., et al. (2022) · Science Advances · doi:10.1126/sciadv.abk0133 · Cited by 70 · see citing works
Super‐Resolution Vibrational Imaging Using Expansion Stimulated Raman Scattering Microscopy
Shi, L., Klimas, A., Gallagher, B. R., Cheng, Z., Fu, F., Wijesekara, P., Miao, Y., Ren, X., Zhao, Y., & Min, W. (2022) · Advanced Science · doi:10.1002/advs.202200315 · Cited by 69 · see citing works
Wilkovitsch, M., Haider, M., Sohr, B., Herrmann, B., Klubnick, J., Weissleder, R., Carlson, J., & Mikula, H. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c07922 · Cited by 66 · see citing works
Current Progress in Expansion Microscopy: Chemical Strategies and Applications
Wen, G., Leen, V., Rohand, T., Sauer, M., & Hofkens, J. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00711 · Cited by 65 · see citing works
A framework for multiplex imaging optimization and reproducible analysis
Eng, J. R., Bucher, E., Hu, Z., Zheng, T., Gibbs, S. L., Chin, K., & Gray, J. W. (2022) · Communications Biology · doi:10.1038/s42003-022-03368-y · Cited by 64 · see citing works
Exploring single cells in space and time during tissue development, homeostasis and regeneration
Mayr, U., Serra, D., & Liberali, P. (2019) · Development · doi:10.1242/dev.176727 · Cited by 63 · see citing works
Rolling circle amplification for single cell analysis and in situ sequencing
Gao, H., Zhang, K., Teng, X., & Li, J. (2019) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2019.115700 · Cited by 63 · see citing works
Temporal and spatial topography of cell proliferation in cancer
Gaglia, G., Kabraji, S. K., Rammos, D., Dai, Y., Verma, A., Wang, S., Mills, C. E., Chung, M., Bergholz, J. S., Coy, S., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00860-9 · Cited by 62 · see citing works
Enablers and challenges of spatial omics, a melting pot of technologies
Alexandrov, T., Sáez-Rodríguez, J., & Saka, S. K. (2023) · Molecular Systems Biology · doi:10.15252/msb.202110571 · Cited by 64 · see citing works
Self-citationCheng, X., Peng, T., Chu, T., Yang, Y., Liu, J., Gao, Q., Cao, C., & Wei, J. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01722-1 · Cited by 64 · see citing works
Single-cell biology: beyond the sum of its parts
Schier, A. F. (2020) · Nature Methods · doi:10.1038/s41592-019-0693-3 · Cited by 56 · see citing works
Vries, N. L. D., Mahfouz, A. E., Koning, F., & de Miranda, N. F. C. C. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01254 · Cited by 58 · see citing works
Qin, X., Xiang, Y., Li, N., Wei, B., Chen, Y., Fang, D., Fang, M., Li, Q., Liu, J., Tang, Y., et al. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2022.114636 · Cited by 60 · see citing works
Credle, J. J., Gunn, J., Sangkhapreecha, P., Monaco, D. R., Zheng, X. A., Tsai, H.-J., Wilbon, A., Morgenlander, W. R., Rastegar, A. T., Dong, Y. W., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00925-y · Cited by 60 · see citing works
Advances in Chromatin and Chromosome Research: Perspectives from Multiple Fields
Agbleke, A. A., Amitai, A., Buenrostro, J. D., Chakrabarti, A., Chu, L., Hansen, A. S., Koenig, K. M., Labade, A. S., Liu, S., Nozaki, T., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.07.003 · Cited by 59 · see citing works
Pooled genetic perturbation screens with image-based phenotypes
Feldman, D., Funk, L., Le, A., Carlson, R. J., Leiken, M. D., Tsai, F., Soong, B., Singh, A., & Blainey, P. C. (2022) · Nature Protocols · doi:10.1038/s41596-021-00653-8 · Cited by 59 · see citing works
Wiener, J., Kokotek, D., Rosowski, S., Lickert, H., & Meier, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-58238-6 · Cited by 58 · see citing works
Programmable DNA-Fueled Electrochemical Analysis of Lung Cancer Exosomes
Sha, L., Bo, B., Yang, F., Li, J., Cao, Y., & Zhao, J. T. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c01318 · Cited by 58 · see citing works
Imaging dendritic cell functions*
Bošnjak, B., Do, K. T. H., Förster, R., & Hammerschmidt, S. I. (2021) · Immunological Reviews · doi:10.1111/imr.13050 · Cited by 58 · see citing works
Mapping the Proteoform Landscape of Five Human Tissues
Drown, B. S., Jooss, K., Melani, R., Lloyd-Jones, C., Camarillo, J., & Kelleher, N. L. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.2c00034 · Cited by 47 · see citing works
Light microscopy based approach for mapping connectivity with molecular specificity
Shen, F. Y., Harrington, M. M., Walker, L. A., Cheng, H. P. J., Boyden, E. S., & Cai, D. (2020) · Nature Communications · doi:10.1038/s41467-020-18422-8 · Cited by 57 · see citing works
Self-citationSpatial proteomics for understanding the tissue microenvironment
Mao, Y., Wang, X., Huang, P., & Tian, R. (2021) · The Analyst · doi:10.1039/d1an00472g · Cited by 53 · see citing works
Hosogane, T., Casanova, R., & Bodenmiller, B. (2023) · Nature Methods · doi:10.1038/s41592-023-01976-y · Cited by 55 · see citing works
Dai, Y., Xu, W. L., Somoza, R. A., Welter, J. F., Caplan, A. I., & Liu, C.-C. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202010648 · Cited by 54 · see citing works
Yapp, C., Novikov, E., Jang, W.-D., Vallius, T., Chen, Y., Cicconet, M., Maliga, Z., Jacobson, C. A., Wei, D., Santagata, S., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-04076-3 · Cited by 54 · see citing works
Self-citationThe Intriguing Landscape of Single‐Cell Protein Analysis
Xie, H., & Ding, X. (2022) · Advanced Science · doi:10.1002/advs.202105932 · Cited by 52 · see citing works
Spatial Transcriptomics for Tumor Heterogeneity Analysis
Li, Q., Zhang, X., & Ke, R. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.906158 · Cited by 52 · see citing works
Expansion microscopy: A powerful nanoscale imaging tool for neuroscientists
Gallagher, B. R., & Zhao, Y. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105362 · Cited by 50 · see citing works
MAUI (MBI Analysis User Interface)—An image processing pipeline for Multiplexed Mass Based Imaging
Baranski, A., Milo, I., Greenbaum, S., Oliveria, J. P., Mrdjen, D., Angelo, M., & Keren, L. (2021) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008887 · Cited by 49 · see citing works
Zhao, D., Kong, Y., Zhao, S., & Xing, H. (2020) · Topics in Current Chemistry · doi:10.1007/s41061-020-00305-7 · Cited by 49 · see citing works
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Bosisio, F. M., Herck, Y. V., Messiaen, J., Bolognesi, M. M., Marcelis, L., Haele, M. V., Cattoretti, G., Antoranz, A., & Smet, F. D. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.918900 · Cited by 46 · see citing works
- Authors
- Saka, S. K., Wang, Y., Kishi, J. Y., Zhu, A., Zeng, Y., Xie, W., Kirli, K., Yapp, C., Cicconet, M., Beliveau, B. J., Lapan, S. W., Yin, S., Lin, M., Boyden, E. S., Kaeser, P. S., Pihan, G., Church, G. M., & Yin, P.
- Affiliations
- Harvard University (US)
- MIT Media Lab (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Saka, Sinem K.
- Wang, Yu
- Yin, Peng
- ORCID
- Venue
- Nature Biotechnology
- Publisher
- openRxiv
- Published
- 2018-12-28
- Volume
- 37
- Issue
- 9
- Pages
- 1080-1090
- ISSN
- 0733-222X (ISSN-L)
- PMC
- PMC6728175
- OpenAlex
- W2968292465
- Cited by
- 485
- References
- 87
- Citations by year
- 2026: 58 · 2025: 74 · 2024: 81 · 2023: 61 · 2022: 87 · 2021: 68 · 2020: 48 · 2019: 7 · 2018: 1
- FWCI
- 17.37
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Nature Biotechnology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Science Foundation (1317291)
- U.S. Department of Defense (N000141612410, N000141812549, N000141612182)
- Howard Hughes Medical Institute
- U.S. Department of Health and Human Services (R01NS083898, 1UG3HL145600/HuBMAP, 1U01MH106011, 1R01GM124401, R01MH113279, RM1 HG008525, 1R01EB018659, 1DP1GM133052, 5K99EY028215-02, 1R01MH113349)
- Damon Runyon Cancer Research Foundation
- Harvard Medical School
- National Institutes of Health (5k99ey028215-02, R01NS083898, RM1 HG008525, R01MH113279, NS072030, 1UG3HL145600/HuBMAP, 1UG3HL145600/HuBMAP, 1R01EB018659, 1U01MH106011, 1DP1GM133052, 1R01GM124401)
- Hansjörg Wyss Institute for Biologically Inspired Engineering, Harvard University
- National Heart, Lung, and Blood Institute (UG3HL145600)
- Office of Naval Research (N00014-16-1-2410, N00014-16-1-2182, N00014-18-1-2549, N00014-16-1-2410, (N00014-18-1-2549, N00014-16-1-2182, N00014)
- National Institute of Mental Health (U01MH106011, R01MH113349, R01MH113279)
- National Human Genome Research Institute (RM1HG008525)
- National Eye Institute (K99 EY028215)
- National Institute of General Medical Sciences (DP1GM133052, R01GM124401)
- National Institute of Neurological Disorders and Stroke (#NS072030, P30NS072030, R01NS083898)
- National Institute of Biomedical Imaging and Bioengineering (R01EB018659)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Keywords
- primer exchange reaction, expansion microscopy, formalin-fixed paraffin-embedded sections, frozen section
- MeSH terms
- Animals, Antibodies, Cell Line, DNA, Fluorescent Dyes, Humans, Immunohistochemistry, Microscopy, Fluorescence, Proteins, Retina, Staining and Labeling, In Situ Hybridization, Fluorescence, Mice, DNA Barcoding, Taxonomic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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