Spage2vec: Unsupervised representation of localized spatial gene expression signatures
Open accessAbstract
Investigations of spatial cellular composition of tissue architectures revealed by multiplexed in situ RNA detection often rely on inaccurate cell segmentation or prior biological knowledge from complementary single‐cell sequencing experiments. Here, we present spage2vec, an unsupervised segmentation‐free approach for decrypting the spatial transcriptomic heterogeneity of complex tissues at subcellular resolution. Spage2vec represents the spatial transcriptomic landscape of tissue samples as a graph and leverages a powerful machine learning graph representation technique to create a lower dimensional representation of local spatial gene expression. We apply spage2vec to mouse brain data from three different in situ transcriptomic assays and to a spatial gene expression dataset consisting of hundreds of individual cells. We show that learned representations encode meaningful biological spatial information of re‐occurring localized gene expression signatures involved in cellular and subcellular processes. Database: Spatial gene expression data are available in Zenodo database at https://doi.org/10.5281/zenodo.3897401. Source code for reproducing analysis results and figures is available in Zenodo database at http://www.doi.org/10.5281/zenodo.4030404.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Applying a joint GCN, VAE, and GAN framework to gene correlation networks initialized with a subset of gene expression matrices can generate disease networks with desired properties.
“Further, applying a joint GCN, VAE, and GAN framework (Section 2.3) to gene correlation networks—initialized with a subset of gene expression matrices—can generate disease networks with the desired properties [149].”
From Graph representation learning in biomedicine and healthcare (2022) · cites this paper as [149]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Adam: A Method for Stochastic Optimization
Kingma, D. P., & Ba, J. (2014) · arXiv · doi:10.48550/arxiv.1412.6980 · Cited by 98,946 · see citing works
Advances in Neural Information Processing Systems 29
Teymur, O., Zygalakis, K., & Calderhead, B. (2016) · Cited by 13,881 · see citing works
Graph Attention NetworksPreprint
Veličković, P., Casanova, A., Liò, P., Cucurull, G., Romero, A., & Bengio, Y. (2017) · arXiv (Cornell University) · doi:10.17863/cam.48429 · Cited by 12,099 · see citing works
A Comprehensive Survey on Graph Neural Networks
Wu, Z., Pan, S., Chen, F., Long, G., Zhang, C., & Yu, P. S. (2021) · IEEE Transactions on Neural Networks and Learning Systems · doi:10.1109/tnnls.2020.2978386 · Cited by 11,000 · see citing works
On Estimation of a Probability Density Function and Mode
Parzen, E. (1962) · The Annals of Mathematical Statistics · doi:10.1214/aoms/1177704472 · Cited by 10,715 · see citing works
Inductive Representation Learning on Large Graphs
Hamilton, W. L., Ying, R., & Leskovec, J. (2017) · arXiv · doi:10.48550/arxiv.1706.02216 · Cited by 10,639 · see citing works
SCANPY: large-scale single-cell gene expression data analysis
Wolf, F. A., Angerer, P., & Theis, F. J. (2018) · Genome Biology · doi:10.1186/s13059-017-1382-0 · Cited by 8,881 · see citing works
Microenvironmental regulation of tumor progression and metastasis
Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994 · see citing works
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction
McInnes, L., Healy, J., & Melville, J. (2018) · arXiv · doi:10.48550/arxiv.1802.03426 · Cited by 7,101 · see citing works
From Louvain to Leiden: guaranteeing well-connected communities
Traag, V. A., Waltman, L., & van Eck, N. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-41695-z · Cited by 5,635 · see citing works
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944 · see citing works
A Comprehensive Survey on Graph Neural Networks
Wu, Z., Pan, S., Chen, F., Long, G., Zhang, C., & Yu, P. (2020) · UTS ePRESS (University of Technology Sydney) · Cited by 3,174 · 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
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
Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH
Eng, C.-H. L., Lawson, M., Zhu, Q., Dries, R., Koulena, N., Takei, Y., Yun, J., Cronin, C., Karp, C., Yuan, G.-C., et al. (2019) · Nature · doi:10.1038/s41586-019-1049-y · Cited by 1,754 · see citing works
Intrinsic and extrinsic contributions to stochasticity in gene expression
Swain, P. S., Elowitz, M. B., & Siggia, E. D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162041399 · Cited by 1,661 · 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
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
Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region
Moffitt, J. R., Bambah-Mukku, D., Eichhorn, S. W., Vaughn, E., Shekhar, K., Perez, J. D., Rubinstein, N. D., Hao, J., Regev, A., Dulac, C., et al. (2018) · Science · doi:10.1126/science.aau5324 · Cited by 1,365 · see citing works
GOATOOLS: A Python library for Gene Ontology analyses
Klopfenstein, D. V., Zhang, L., Pedersen, B. S., Ramírez, F., Vesztrocy, A. W., Naldi, A., Mungall, C., Yunes, J. M., Botvinnik, O. B., Weigel, M., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-28948-z · Cited by 1,307 · see citing works
Exponential scaling of single-cell RNA-seq in the past decade
Svensson, V., Vento‐Tormo, R., & Teichmann, S. A. (2018) · Nature Protocols · doi:10.1038/nprot.2017.149 · Cited by 936 · see citing works
Cajigas, I. J., Tushev, G., Will, T. J., tom Dieck, S., Fuerst, N., & Schuman, E. M. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.036 · Cited by 709 · 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
Spatial organization of the somatosensory cortex revealed by osmFISH
Codeluppi, S., Borm, L. E., Zeisel, A., Manno, G. L., van Lunteren, J. A., Svensson, C. I., & Linnarsson, S. (2018) · Nature Methods · doi:10.1038/s41592-018-0175-z · Cited by 649 · see citing works
In the right place at the right time: visualizing and understanding mRNA localization
Buxbaum, A. R., Haimovich, G., & Singer, R. H. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3918 · Cited by 610 · see citing works
Design and Analysis of Single-Cell Sequencing Experiments
Grün, D., & van Oudenaarden, A. (2015) · Cell · doi:10.1016/j.cell.2015.10.039 · Cited by 536 · see citing works
Miller, S., Yasuda, M., Coats, J., Jones, Y., Martone, M. E., & Mayford, M. R. (2002) · Neuron · doi:10.1016/s0896-6273(02)00978-9 · Cited by 507 · see citing works
Subcellular mRNA Localization in Animal Cells and Why It Matters
Holt, C. E., & Bullock, S. L. (2009) · Science · doi:10.1126/science.1176488 · Cited by 418 · see citing works
Translational control of localized mRNAs: restricting protein synthesis in space and time
Besse, F., & Ephrussi, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2548 · Cited by 373 · see citing works
Brain micro-ecologies: neural stem cell niches in the adult mammalian brain
Riquelme, P. A., Drapeau, E., & Doetsch, F. K. (2007) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.2016 · Cited by 277 · see citing works
Local translation of extranuclear lamin B promotes axon maintenance
Yoon, B. C., Jung, H., Dwivedy, A., O'Hare, C. M., Zivraj, K. H., & Holt, C. E. (2012) · Cell · doi:10.1016/j.cell.2011.11.064 · Cited by 263 · see citing works
Zhu, Q., Shah, S., Dries, R., Cai, L., & Yuan, G. (2018) · Nature Biotechnology · doi:10.1038/nbt.4260 · Cited by 248 · see citing works
Probabilistic cell typing enables fine mapping of closely related cell types in situ
Qian, X., Harris, K. D., Hauling, T., Nicoloutsopoulos, D., Muñoz‐Manchado, A. B., Skene, N., Hjerling‐Leffler, J., & Nilsson, M. F. (2019) · Nature Methods · doi:10.1038/s41592-019-0631-4 · Cited by 230 · see citing works
Subcellular Knockout of Importin β1 Perturbs Axonal Retrograde Signaling
Perry, R. B., Doron‐Mandel, E., Iavnilovitch, E., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.05.033 · Cited by 172 · see citing works
Stem Cell Niche: Microenvironment and Beyond
Zhang, J., & Li, L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r700043200 · Cited by 130 · see citing works
Cell segmentation-free inference of cell types from in situ transcriptomics data
Park, J., Choi, W., Tiesmeyer, S., Long, B., Borm, L. E., Garren, E. J., Nguyen, T. N., Tasic, B., Codeluppi, S., Graf, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23807-4 · Cited by 116 · see citing works
The travels of mRNAs in neurons: do they know where they are going?
Das, S., Singer, R. H., & Yoon, Y. J. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.01.016 · Cited by 81 · see citing works
Making and breaking synapses through local mRNA regulation
Swanger, S. A., & Bassell, G. J. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.04.002 · Cited by 72 · see citing works
Solorzano, L., Partel, G., & Wählby, C. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa541 · Cited by 46 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [32]Maas AL, Hannun AY & Ng AY (2013) Rectifier nonlinearities improve neural network acoustic models. In Proc. icml 30, 3. http://robotics.stanford.edu/~amaas/papers/relu_hybrid_icml2013_final.pdf
Cited by
Sorted by citations
Hu, J., Li, X., Coleman, K., Schroeder, A., Ma, N., Irwin, D. J., Lee, E. B., Shinohara, R. T., & Li, M. (2021) · Nature Methods · doi:10.1038/s41592-021-01255-8 · Cited by 1,113 · see citing works
Graph representation learning in biomedicine and healthcare
Li, M. M., Huang, K., & Zitnik, M. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00942-x · Cited by 294 · see citing works
“As a result, spatial transcriptomics data can be used to construct cell graphs 148 , spatial gene-expression graphs 149 , gene-co-expression networks or molecular-similarity graphs 35 .”
Graph representation learning for single-cell biology
Hetzel, L., Fischer, D. S., Günnemann, S., & Theis, F. J. (2021) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2021.05.008 · Cited by 55 · see citing works
Graph neural networks for single-cell omics data: a review of approaches and applications
Li, S., Hua, H., & Chen, S. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf109 · Cited by 43 · see citing works
- Authors
- Partel, G., & Wählby, C.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Partel, Gabriele
- Wählby, Carolina
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2020-10-11
- Volume
- 288
- Issue
- 6
- Pages
- 1859-1870
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- PMC
- PMC7983892
- OpenAlex
- W3087998689
- Cited by
- 50
- References
- 39
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 11 · 2022: 11 · 2021: 9 · 2020: 1
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- FEBS Journal (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Funders
- H2020 European Research Council (682810)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- spatial transcriptomics, graph representation learning, unsupervised feature learning, graph neural networks, mouse brain, subcellular resolution
- MeSH terms
- Animals, Cell Line, Fibroblasts, Humans, Somatosensory Cortex, Cluster Analysis, Neural Networks, Computer, Computational Biology, Internet, Gene Expression Profiling, Mice, Gene Regulatory Networks, CA1 Region, Hippocampal, Transcriptome, Gene Ontology
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 ›
Are you an author, or do you see a problem with this page? Request a review