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A Bayesian nonparametric approach to super-resolution single-molecule localization. (English) Zbl 1498.62213

Summary: We consider the problem of single-molecule identification in super-resolution microscopy. Super-resolution microscopy overcomes the diffraction limit by localizing individual fluorescing molecules in a field of view. This is particularly difficult since each individual molecule appears and disappears randomly across time and because the total number of molecules in the field of view is unknown. Additionally, data sets acquired with super-resolution microscopes can contain a large number of spurious fluorescent fluctuations caused by background noise.
To address these problems, we present a Bayesian nonparametric framework capable of identifying individual emitting molecules in super-resolved time series. We tackle the localization problem in the case in which each individual molecule is already localized in space. First, we collapse observations in time and develop a fast algorithm that builds upon the Dirichlet process. Next, we augment the model to account for the temporal aspect of fluorophore photophysics. Finally, we assess the performance of our methods with ground-truth data sets having known biological structure.

MSC:

62P10 Applications of statistics to biology and medical sciences; meta analysis
62G05 Nonparametric estimation
62F15 Bayesian inference
62M30 Inference from spatial processes

Software:

Fiji; ThunderSTORM
PDFBibTeX XMLCite
Full Text: DOI

References:

[1] Abbe, E. (1873). Beiträge zur Theorie des Mikroskops und der mikroskopischen Wahrnehmung. Arch. Mikrosk. Anat. 9 413-418. · doi:10.1007/BF02956173
[2] Airy, G. B. (1835). On the diffraction of an object-glass with circular aperture. Trans. of the Cambridge Philosoph. Soc. 5 283-291.
[3] Annibale, P., Scarselli, M., Kodiyan, A. and Radenovic, A. (2010). Photoactivatable fluorescent protein mEos2 displays repeated photoactivation after a long-lived dark state in the red photoconverted form. J. Phys. Chem. Lett. 1 1506-1510.
[4] Annibale, P., Vanni, S., Scarselli, M., Rothlisberger, U. and Radenovic, A. (2011a). Identification of clustering artifacts in photoactivated localization microscopy. Nat. Methods 8 527-528.
[5] Annibale, P., Vanni, S., Scarselli, M., Rothlisberger, U. and Radenovic, A. (2011). Quantitative photo activated localization microscopy: Unraveling the effects of photoblinking. PLoS ONE 6 e22678. · doi:10.1371/journal.pone.0022678
[6] Archambeau, C., Lakshminarayanan, B. and Bouchard, G. (2014). Latent IBP compound Dirichlet allocation. IEEE Trans. Pattern Anal. Mach. Intell. 37 321-333.
[7] Beck, M. and Hurt, E. (2017). The nuclear pore complex: Understanding its function through structural insight. Nat. Rev. Mol. Cel. Biol. 18.
[8] Betzig, E., Patterson, G. H., Sougrat, R., Lindwasser, O. W., Olenych, S., Bonifacino, J. S., Davidson, M. W., Lippincott-Schwartz, J. and Hess, H. F. (2006). Imaging intracellular fluorescent proteins at nanometer resolution. Science 313 1642-1645.
[9] Blei, D. M. and Jordan, M. I. (2006). Variational inference for Dirichlet process mixtures. Bayesian Anal. 1 121-143. · Zbl 1331.62259 · doi:10.1214/06-BA104
[10] Blei, D. M., Kucukelbir, A. and McAuliffe, J. D. (2017). Variational inference: A review for statisticians. J. Amer. Statist. Assoc. 112 859-877. · doi:10.1080/01621459.2017.1285773
[11] Braun, M. and McAuliffe, J. (2010). Variational inference for large-scale models of discrete choice. J. Amer. Statist. Assoc. 105 324-335. · Zbl 1397.62103 · doi:10.1198/jasa.2009.tm08030
[12] Broderick, T., Jordan, M. I. and Pitman, J. (2013). Cluster and feature modeling from combinatorial stochastic processes. Statist. Sci. 28 289-312. · Zbl 1331.62124 · doi:10.1214/13-STS434
[13] D’Angelo, M. A. and Hetzer, M. W. (2008). Structure, dynamics and function of nuclear pore complexes. Trends Cell Biol. 18 456-466.
[14] Dempsey, G. T., Vaughan, J. C., Chen, K. H., Bates, M. and Zhuang, X. (2011). Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging. Nat. Methods 8 1027.
[15] Deschout, H. . (2014). Precisely and accurately localizing single emitters in fluorescence microscopy. Nat. Methods 11 253-266.
[16] Escobar, M. D. and West, M. (1995). Bayesian density estimation and inference using mixtures. J. Amer. Statist. Assoc. 90 577-588. · Zbl 0826.62021
[17] Ester, M., Kriegel, H.-P., Sander, J. and Xu, X. (1996). A density-based algorithm for discovering clusters a density-based algorithm for discovering clusters in large spatial databases with noise. In Proceedings of the Second International Conference on Knowledge Discovery and Data Mining. KDD’96 226-231. AAAI Press, Menlo Park.
[18] Ewens, W. J.(1990). Population genetics theory—the past and the future. In Mathematical and Statistical Developments of Evolutionary Theory (Montreal, PQ, 1987). NATO Adv. Sci. Inst. Ser. C Math. Phys. Sci. 299 177-227. Kluwer Academic, Dordrecht. · Zbl 0718.92010
[19] Faisal, A., Gillberg, J., Peltonen, J., Leen, G. and Kaski, S. (2012). Sparse nonparametric topic model for transfer learning. In European Symposium on Artificial Neural Networks.
[20] Ferguson, T. S. (1973). A Bayesian analysis of some nonparametric problems. Ann. Statist. 1 209-230. · Zbl 0255.62037
[21] Finkel, R. A. and Bentley, J. L. (1974). Quad trees a data structure for retrieval on composite keys. Acta Inform. 4 1-9. · Zbl 0278.68030
[22] Foti, N., Futoma, J., Rockmore, D. and Williamson, S. (2013). A unifying representation for a class of dependent random measures. In Proceedings of the Sixteenth International Conference on Artificial Intelligence and Statistics. Proceedings of Machine Learning Research 31.
[23] Fox, E., Jordan, M. I., Sudderth, E. B. and Willsky, A. S. (2009). Sharing features among dynamical systems with beta processes. In Advances in Neural Information Processing Systems 549-557.
[24] Gabitto, M. I., Marie-Nelly, H., Pakman, A., Pataki, A., Darzacq, X. and Jordan, M. I. (2021). Supplement to “A Bayesian nonparametric approach to super-resolution single-molecule localization.” https://doi.org/10.1214/21-AOAS1441SUPPA, https://doi.org/10.1214/21-AOAS1441SUPPB
[25] Gael, J. V., Teh, Y. W. and Ghahramani, Z. (2009). The infinite factorial hidden Markov model. In Advances in Neural Information Processing Systems 1697-1704.
[26] Gelfand, A. E. and Smith, A. F. M. (1990). Sampling-based approaches to calculating marginal densities. J. Amer. Statist. Assoc. 85 398-409. · Zbl 0702.62020
[27] Hansen, A. S., Cattoglio, C., Darzacq, X. and Tjian, R. (2018). Recent evidence that TADs and chromatin loops are dynamic structures. Nucleus 9 20-32. · doi:10.1080/19491034.2017.1389365
[28] Heilemann, M., Margeat, E., Kasper, R., Sauer, M. and Tinnefeld, P. (2005). Carbocyanine dyes as efficient reversible single-molecule optical switch. J. Am. Chem. Soc. 127 3801-3806.
[29] Heilemann, M., Dedecker, P., Hofkens, J. and Sauer, M. (2009). Photoswitches: Key molecules for subdiffraction-resolution fluorescence imaging and molecular quantification. Laser Photonics Rev. 3 180-202.
[30] Holden, S. J., Uphoff, S. and Kapanidis, A. N. (2011). DAOSTORM: An algorithm for high-density super-resolution microscopy. Nat. Methods 8 279-280. · doi:10.1038/nmeth0411-279
[31] Huang, Z. L. . (2011). Localization-based super-resolution microscopy with an sCMOS camera. Opt. Express 19 19156-19168.
[32] Huggins, J. H. and Wood, F. (2014). Infinite structured hidden semi-Markov models. Preprint. Available at arXiv:1407.0044.
[33] Hughes, M., Kim, D. I. and Sudderth, E. (2015). Reliable and scalable variational inference for the hierarchical Dirichlet process. In Artificial Intelligence and Statistics 370-378.
[34] Hummer, G., Fricke, F. and Heilemann, M. (2016). Model-independent counting of molecules in single-molecule localization microscopy. Mol. Biol. Cell 27 3637-3644. · doi:10.1091/mbc.E16-07-0525
[35] Ickstadt, K. and Wolpert, R. L. (1999). Spatial regression for marked point processes. In Bayesian Statistics, 6 (Alcoceber, 1998) 323-341. Oxford Univ. Press, New York. · Zbl 0974.62089
[36] Jordan, M. I., Gharamani, Z., Jaakkola, T. and Saul, L. (1999). An introduction to variational methods for graphical models. Mach. Learn. 37 183-233. · Zbl 0945.68164
[37] Kaplan, C. and Ewers, H. (2015). Optimized sample preparation for single-molecule localization-based superresolution microscopy in yeast. Nat. Protoc. 10 1007-1021.
[38] Kapoor-Kaushik, N. . (2016). Distinct mechanisms regulate Lck spatial organization in activated T cells. Front. Immunol. 7 83.
[39] Kim, S. J., Fernandez-Martinez, J., Nudelman, I., Shi, Y., Zhang, W., Raveh, B., Herricks, T., Slaughter, B. D., Hogan, J. A. et al. (2018). Integrative structure and functional anatomy of a nuclear pore complex. Nature 555 475.
[40] Košuta, T., Cullell-Dalmau, M., Zanacchi, F. C. and Manzo, C. (2020). Bayesian analysis of data from segmented super-resolution images for quantifying protein clustering. Phys. Chem. Chem. Phys. 22 1107-1114. · doi:10.1039/c9cp05616e
[41] Kottas, A. and Sansó, B. (2007). Bayesian mixture modeling for spatial Poisson process intensities, with applications to extreme value analysis. J. Statist. Plann. Inference 137 3151-3163. · Zbl 1114.62100 · doi:10.1016/j.jspi.2006.05.022
[42] Lee, S.-H., Shin, J. Y., Lee, A. and Bustamante, C. (2012). Counting single photoactivatable fluorescent molecules by photoactivated localization microscopy (PALM). Proc. Natl. Acad. Sci. USA 109 17436-17441.
[43] Li, Y., Mund, M., Hoess, P., Deschamps, J., Matti, U., Nijmeijer, B., Sabinina, V. J., Ellenberg, J., Schoen, I. et al. (2018). Real-time 3D single-molecule localization using experimental point spread functions. Nat. Methods 15 367-369. · doi:10.1038/nmeth.4661
[44] Lippincott-Schwartz, J. and Patterson, G. H. (2009). Photoactivatable fluorescent proteins for diffraction-limited and super-resolution imaging. Trends Cell Biol. 19 555-565.
[45] Neal, R. M. (1992). Bayesian mixture modeling. In Proceedings of the Workshop on Maximum Entropy and Bayesian Methods of Statistical Analysis 11 197-211. · Zbl 0829.62033
[46] Nehme, E., Freedman, D., Gordon, R., Ferdman, B., Weiss, L. E., Alalouf, O., Orange, R. and Michaeli, T. (2019). DeepSTORM3D: Dense three dimensional localization microscopy and point spread function design by deep learning. Int. J. Image Video Process.
[47] Nicovich, P. R., Owen, D. M. and Gaus, K. (2017). Turning single-molecule localization microscopy into a quantitative bioanalytical tool. Nat. Protoc. 12 453-460. · doi:10.1038/nprot.2016.166
[48] Nino, D., Rafiei, N., Wang, Y., Zilman, A. and Milstein, J. N. (2017). Molecular counting with localization microscopy: A Bayesian estimate based on fluorophore statistics. Biophys. J. 112 1777-1785.
[49] Olivier, N., Keller, D., Gönczy, P. and Manley, S. (2011). Resolution doubling in 3D-STORM imaging through improved buffers. PLoS ONE 8 e69004.
[50] Ovesnỳ, M., Křížek, P., Borkovec, J., Švindrych, Z. and Hagen, G. M. (2014). ThunderSTORM: A comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging. Bioinformatics 30 2389-2390.
[51] Owen, D. M. . (2010). PALM imaging and cluster analysis of protein heterogeneity at the cell surface. J. Biophotonics 3 446-454.
[52] Perrone, V., Jenkins, P. A., Spanò, D. and Teh, Y. W. (2017). Poisson random fields for dynamic feature models. J. Mach. Learn. Res. 18 Paper No. 127, 45. · Zbl 1442.62070
[53] Pertsinidis, A., Zhang, Y. and Chu, S. (2010). Subnanometre single-molecule localization, registration and distance measurements. Nature 466 647-651.
[54] Puchner, E. M., Walter, J. M., Kasper, R., Huang, B. and Lim, W. A. (2013). Counting molecules in single organelles with superresolution microscopy allows tracking of the endosome maturation trajectory. Proc. Natl. Acad. Sci. USA 110 16015-16020.
[55] Rasmussen, C. E. (2000). The infinite Gaussian mixture model. Adv. Neural Inf. Process. Syst. 12.
[56] Regier, J., Miller, A. C., Schlegel, D., Adams, R. P., McAuliffe, J. D. and Prabhat (2019). Approximate inference for constructing astronomical catalogs from images. Ann. Appl. Stat. 13 1884-1926. · Zbl 1433.62336 · doi:10.1214/19-AOAS1258
[57] Rollins, G. C., Shin, J. Y., Bustamante, C. and Pressé, S. (2015). Stochastic approach to the molecular counting problem in superresolution microscopy. Proc. Natl. Acad. Sci. USA 112 E110-E118.
[58] Rossy, J., Cohen, E., Gaus, K. and Owen, D. M. (2014). Method for co-cluster analysis in multichannel single-molecule localisation data. Histochem. Cell Biol. 141 605-612.
[59] Rosten, E., Jones, G. E. and Cox, S. (2013). ImageJ plug-in for Bayesian analysis of blinking and bleaching. Nat. Methods 10 97.
[60] Roy, A., Field, M. J., Adam, V. and Bourgeois, D. (2011). The nature of transient dark states in a photoactivatable fluorescent protein. J. Am. Chem. Soc. 133 18586-18589.
[61] Rubin-Delanchy, P., Burn, G. L., Griffié, J., Williamson, D. J., Heard, N. A., Cope, A. P. and Owen, D. M. (2015). Bayesian cluster identification in single-molecule localization microscopy data. Nat. Methods 12 1072-1076. · doi:10.1038/nmeth.3612
[62] Rust, M. J., Bates, M. and Zhuang, X. (2006). Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat. Methods 3 793-795. · doi:10.1038/nmeth929
[63] Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S. et al. (2012). Fiji: An open-source platform for biological-image analysis. Nat. Methods 9 676.
[64] Schubert, E., Sander, J., Ester, M., Kriegel, H.-P. and Xu, X. (2017). DBSCAN revisited, revisited: Why and how you should (still) use DBSCAN. ACM Trans. Database Syst. 42 Art. 19, 21. · doi:10.1145/3068335
[65] Sengupta, P. . (2011). Probing protein heterogeneity in the plasma membrane using PALM and pair correlation analysis. Nat. Methods 8 969-975.
[66] Sergé, A., Bertaux, N., Rigneault, H. and Marguet, D. (2008). Multiple-target tracing (MTT) algorithm probes molecular dynamics at cell surface. Protocol Exchange, https://doi.org/10.1038/nprot.2008.128.
[67] Sethuraman, J. (1994). A constructive definition of Dirichlet priors. Statist. Sinica 4 639-650. · Zbl 0823.62007
[68] Shcherbakova, D. M., Sengupta, P., Lippincott-Schwartz, J. and Verkhusha, V. V. (2014). Photocontrollable fluorescent proteins for superresolution imaging. Annu. Rev. Biophys. 43 303-329.
[69] Small, A. and Stahlheber, S. (2014). Fluorophore localization algorithms for super-resolution microscopy. Nat. Methods 11 267-279. · doi:10.1038/nmeth.2844
[70] Specht, C. G., Izeddin, I., Rodriguez, P. C., El Beheiry, M., Rostaing, P., Darzacq, X., Dahan, M. and Triller, A. (2013). Quantitative nanoscopy of inhibitory synapses: Counting gephyrin molecules and receptor binding sites. Neuron 79 308-321.
[71] Speiser, A., Turaga, S. C. and Macke, J. H. (2019). Teaching deep neural networks to localize sources in super-resolution microscopy by combining simulation-based learning and unsupervised learning. Available at arXiv:abs/1907.00770.
[72] Sun, R., Archer, E. and Paninski, L. (2017). Scalable variational inference for super resolution microscopy. In Proceedings of the 20th International Conference on Artificial Intelligence and Statistics 1057-1065.
[73] Sun, S., Paisley, J. and Liu, Q. (2017). Location dependent Dirichlet processes. In International Conference on Intelligent Science and Big Data Engineering 64-76. Springer, Berlin.
[74] Szymborska, A., De Marco, A., Daigle, N., Cordes, V. C., Briggs, J. A. and Ellenberg, J. (2013). Nuclear pore scaffold structure analyzed by super-resolution microscopy and particle averaging. Science 341 655-658.
[75] Taddy, M. A. and Kottas, A. (2012). Mixture modeling for marked Poisson processes. Bayesian Anal. 7 335-361. · Zbl 1330.62200 · doi:10.1214/12-BA711
[76] Teh, Y. W., Jordan, M. I., Beal, M. J. and Blei, D. M. (2006). Hierarchical Dirichlet processes. J. Amer. Statist. Assoc. 101 1566-1581. · Zbl 1171.62349 · doi:10.1198/016214506000000302
[77] Turner, R. E. and Sahani, M. (2011). Two problems with variational expectation maximisation for time series models. In Bayesian Time Series Models 104-124. Cambridge Univ. Press, Cambridge.
[78] Valera, I., Ruiz, F. J. and Perez-Cruz, F. (2015). Infinite factorial unbounded-state hidden Markov model. IEEE Trans. Pattern Anal. Mach. Intell. 38 1816-1828.
[79] van de Linde, S., Heilemann, M. and Sauer, M. (2012). Live-cell super-resolution imaging with synthetic fluorophores. Annu. Rev. Phys. Chem. 63 519-540.
[80] Veatch, S. L. . (2012). Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting. PLoS ONE 7 e31457.
[81] Wainwright, M. J. and Jordan, M. I. (2008). Graphical models, exponential families, and variational inference. Found. Trends Mach. Learn. 1 1-305. · Zbl 1193.62107
[82] Williamson, S., Wang, C., Heller, K. A. and Blei, D. M. (2010). The IBP compound Dirichlet process and its application to focused topic modeling. In Proceedings of the 27th International Conference on Machine Learning (ICML-10) 1151-1158. Citeseer.
[83] Xu, K., Zhong, G. and Zhuang, X. (2013). Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons. Science 339 452-456.
[84] Zanacchi, F. C., Manzo, C., Alvarez, A. S., Derr, N. D., Garcia-Parajo, M. F. and Lakadamyali, M. (2017). A DNA origami platform for quantifying protein copy number in super-resolution. Nat. Methods 14 789-792 · doi:10.1038/nmeth.4342
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