Skip to main content

Advertisement

Log in

Quantitative Arbor Analytics: Unsupervised Harmonic Co-Clustering of Populations of Brain Cell Arbors Based on L-Measure

  • Original Article
  • Published:
Neuroinformatics Aims and scope Submit manuscript

Abstract

This paper presents a robust unsupervised harmonic co-clustering method for profiling arbor morphologies for ensembles of reconstructed brain cells (e.g., neurons, microglia) based on quantitative measurements of the cellular arbors. Specifically, this method can identify groups and sub-groups of cells with similar arbor morphologies, and simultaneously identify the hierarchical grouping patterns among the quantitative arbor measurements. The robustness of the proposed algorithm derives from use of the diffusion distance measure for comparing multivariate data points, harmonic analysis theory, and a Haar-like wavelet basis for multivariate data smoothing. This algorithm is designed to be practically usable, and is embedded into the actively linked three-dimensional (3-D) visualization and analytics system in the free and open source FARSIGHT image analysis toolkit for interactive exploratory population-scale neuroanatomic studies. Studies on synthetic datasets demonstrate its superiority in clustering data matrices compared to recent hierarchical clustering algorithms. Studies on heterogeneous ensembles of real neuronal 3-D reconstructions drawn from the NeuroMorpho database show that the proposed method identifies meaningful grouping patterns among neurons based on arbor morphology, and revealing the underlying morphological differences.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Arisi, G. M., & Garcia-Cairasco, N. (2007). Doublecortin-positive newly born granule cells of hippocampus have abnormal apical dendritic morphology in the pilocarpine model of temporal lobe epilepsy. Brain Research, 1165, 126–134.

    Article  PubMed  CAS  Google Scholar 

  • Ascoli, G. A., Donohue, D. E., & Halavi, M. (2007). NeuroMorpho. Org: a central resource for neuronal morphologies. The Journal of Neuroscience, 27(35), 9247–9251.

    Article  PubMed  CAS  Google Scholar 

  • Balasko, B., Abonyi, J., & Feil, B. (2005). Fuzzy clustering and data analysis toolbox. Department of Process Engineering, University of Veszprem, Veszprem.

  • Banerjee, A., Dhillon, I., Ghosh, J., Merugu, S., & Modha, D. S. (2004, August). A generalized maximum entropy approach to bregman co-clustering and matrix approximation. In Proceedings of the tenth ACM SIGKDD international conference on Knowledge discovery and data mining (pp. 509–514). ACM.

  • Bausch, S. B., He, S., Petrova, Y., Wang, X. M., & McNamara, J. O. (2006). Plasticity of both excitatory and inhibitory synapses is associated with seizures induced by removal of chronic blockade of activity in cultured hippocampus. Journal of Neurophysiology, 96(4), 2151.

    Article  PubMed  CAS  Google Scholar 

  • Brameier, M., & Wiuf, C. (2007). Co-clustering and visualization of gene expression data and gene ontology terms for Saccharomyces cerevisiae using self-organizing maps. Journal of Biomedical Informatics, 40(2), 160–173.

    Article  PubMed  CAS  Google Scholar 

  • Cannon, R. C., et al. (1998). An on-line archive of reconstructed hippocampal neurons. Journal of Neuroscience Methods, 84(1–2), 49–54.

    Article  PubMed  CAS  Google Scholar 

  • Carnevale, N. T., Tsai, K. Y., Claiborne, B. J., & Brown, T. H. (1997). Comparative electrotonic analysis of three classes of rat hippocampal neurons. Journal of Neurophysiology, 78(2), 703–720.

    PubMed  CAS  Google Scholar 

  • Chen, C. C., Abrams, S., Pinhas, A., & Brumberg, J. C. (2009). Morphological heterogeneity of layer VI neurons in mouse barrel cortex. Journal of Comparative Neurology, 512(6), 726–746.

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen, G., Sullivan, P. F., & Kosorok, M. R. (2013). Biclustering with heterogeneous variance. Proceedings of the National Academy of Sciences, 110(30), 12253–12258.

    Article  Google Scholar 

  • Cheng, Y., & Church, G. M. (2000, August). Biclustering of expression data. In Proceedings of the eighth international conference on intelligent systems for molecular biology (Vol. 8, pp. 93–103).

  • Chitwood, R. A., Hubbard, A., & Jaffe, D. B. (1999). Passive electrotonic properties of rat hippocampal CA3 interneurones. The Journal of Physiology, 515(3), 743–756.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Coifman, R. R., & Gavish, M. (2011). Harmonic analysis of digital data bases. In Wavelets and Multiscale analysis (pp. 161–197). Boston: Birkhäuser.

  • Coifman, R. R., & Lafon, S. (2006). Diffusion maps. Applied and Computational Harmonic Analysis, 21(1), 5–30.

    Article  Google Scholar 

  • Coifman, R. R., & Maggioni, M. (2006). Diffusion wavelets. Applied and Computational Harmonic Analysis, 21(1), 53–94.

    Article  Google Scholar 

  • Dhillon, I. S., Mallela, S., & Modha, D. S. (2003, August). Information-theoretic co-clustering. In Proceedings of the ninth ACM SIGKDD international conference on knowledge discovery and data mining (pp. 89–98). ACM.

  • Ding, C., He, X., & Simon, H. D. (2005, April). On the equivalence of nonnegative matrix factorization and spectral clustering. In Proc. SIAM data mining conf (No. 4, pp. 606–610).

  • Gavish, M., Nadler, B., & Coifman, R. R. (2010). Multiscale wavelets on trees, graphs and high dimensional data: Theory and applications to semi supervised learning. In Proceedings of the 27th International Conference on Machine Learning (ICML-10) (pp. 367–374).

  • George, T., & Merugu, S. (2005, November). A scalable collaborative filtering framework based on co-clustering. In Data Mining, Fifth IEEE International Conference on (pp. 4-pp). IEEE.

  • Getz, G., Gal, H., Kela, I., Notterman, D. A., & Domany, E. (2003). Coupled two-way clustering analysis of breast cancer and colon cancer gene expression data. Bioinformatics, 19(9), 1079–1089.

    Article  PubMed  CAS  Google Scholar 

  • Golding, N. L., Mickus, T. J., Katz, Y., Kath, W. L., & Spruston, N. (2005). Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites. The Journal of Physiology, 568(1), 69–82.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gulyás, A. I., Megı́as, M., Emri, Z., & Freund, T. F. (1999). Total number and ratio of excitatory and inhibitory synapses converging onto single interneurons of different types in the CA1 area of the rat hippocampus. The Journal of Neuroscience, 19(22), 10082–10097.

    PubMed  Google Scholar 

  • Halavi, M., Hamilton, K. A., Parekh, R., & Ascoli, G. A. (2012). Digital reconstructions of neuronal morphology: three decades of research trends. Frontiers in Neuroscience, 6, 49.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hartigan, J. A. (1972). Direct clustering of a data matrix. Journal of the American Statistical Association, 67(337), 123–129.

    Article  Google Scholar 

  • Ho, S. Y., Chao, C. Y., Huang, H. L., Chiu, T. W., Charoenkwan, P., & Hwang, E. (2011). NeurphologyJ: an automatic neuronal morphology quantification method and its application in pharmacological discovery. BMC Bioinformatics, 12(1), 230.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ishizuka, N., Cowan, W. M., & Amaral, D. G. (1995). A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus. Journal of Comparative Neurology, 362(1), 17–45.

    Article  PubMed  CAS  Google Scholar 

  • Jinushi-Nakao, S., Arvind, R., Amikura, R., Kinameri, E., Liu, A. W., & Moore, A. W. (2007). Knot/Collier and cut control different aspects of dendrite cytoskeleton and synergize to define final arbor shape. Neuron, 56(6), 963–978.

    Article  PubMed  CAS  Google Scholar 

  • Krieger, P., Kuner, T., & Sakmann, B. (2007). Synaptic connections between layer 5B pyramidal neurons in mouse somatosensory cortex are independent of apical dendrite bundling. The Journal of Neuroscience, 27(43), 11473–11482.

    Article  PubMed  CAS  Google Scholar 

  • Kullback, S., & Leibler, R. A. (1951). On information and sufficiency. Annals of Mathematical Statistics, 22(1), 79–86.

    Article  Google Scholar 

  • Lafon, S. S. (2004). Diffusion maps and geometric harmonics (Doctoral dissertation, Yale University).

  • Lee, F. H., Kaidanovich-Beilin, O., Roder, J. C., Woodgett, J. R., & Wong, A. H. (2011). Genetic inactivation of GSK3α rescues spine deficits in Disc1 − L100P mutant mice. Schizophrenia Research, 129(1), 74–79.

    Article  PubMed  Google Scholar 

  • Lu, Y., Trett, K., Shain, W., Carin, L., Coifman, R., & Roysam, B. (2013, April). Quantitative profiling of microglia populations using harmonic co-clustering of arbor morphology measurements. In Biomedical Imaging (ISBI), 2013 IEEE 10th International Symposium on (pp. 1360–1363). IEEE.

  • Luisi, J., Narayanaswamy, A., Galbreath, Z., & Roysam, B. (2011). The FARSIGHT trace editor: an open source tool for 3-D inspection and efficient pattern analysis aided editing of automated neuronal reconstructions. Neuroinformatics, 9(2), 305–315.

    Article  PubMed  Google Scholar 

  • Meijering, E. (2010). Neuron tracing in perspective. Cytometry. Part A, 77(7), 693–704.

    Article  Google Scholar 

  • Nadler, B., Lafon, S., Coifman, R., & Kevrekidis, I. (2005, December). Diffusion maps, spectral clustering and eigenfunctions of Fokker-Planck operators. In NIPS.

  • Padmanabhan, R. K., Somasundar, V. H., Griffith, S. D., Zhu, J., Samoyedny, D., Tan, K. S., & Lee, W. M. (2014). An active learning approach for rapid characterization of endothelial cells in human tumors. PloS One, 9(3), e90495.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Peng, H., Long, F., & Myers, G. (2011). Automatic 3D neuron tracing using all-path pruning. Bioinformatics, 27(13), i239–i247.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Powers, D. M. W. (2011). Evaluation: from precision, recall and f-measure to roc., informedness, markedness & correlation. Journal of Machine Learning Technologies, 2(1), 37–63.

    Google Scholar 

  • Rey-Villamizar, N. (2014). Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python. Frontiers in Neuroinformatics, 8, 39.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rocher, A. B., Crimins, J. L., Amatrudo, J. M., Kinson, M. S., Todd-Brown, M. A., Lewis, J., & Luebke, J. I. (2010). Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs. Experimental Neurology, 223(2), 385–393.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Scorcioni, R., Polavaram, S., & Ascoli, G. A. (2008). L-Measure: a web-accessible tool for the analysis, comparison and search of digital reconstructions of neuronal morphologies. Nature Protocols, 3(5), 866–876.

    Article  PubMed  CAS  Google Scholar 

  • Scorza, C. A., Araujo, B. H. S., Leite, L. A., Torres, L. B., Otalora, L. F. P., Oliveira, M. S., & Cavalheiro, E. A. (2011). Morphological and electrophysiological properties of pyramidal-like neurons in the stratum oriens of Cornu ammonis 1 and Cornu ammonis 2 area of Proechimys. Neuroscience, 177, 252–268.

    Article  PubMed  CAS  Google Scholar 

  • Sibson, R. (1973). SLINK: an optimally efficient algorithm for the single-link cluster method. The Computer Journal, 16(1), 30–34.

    Article  Google Scholar 

  • Smit-Rigter, L. A., Noorlander, C. W., von Oerthel, L., Chameau, P., Smidt, M. P., & van Hooft, J. A. (2012). Prenatal fluoxetine exposure induces life-long serotonin 5-HT3 receptor-dependent cortical abnormalities and anxiety-like behavior. Neuropharmacology, 62(2), 865–870.

    Article  PubMed  CAS  Google Scholar 

  • Strömberg, J. O. (1998). Computation with wavelets in higher dimensions. In Proceedings of the International Congress of Mathematicians (Vol. 3, pp. 523–532).

  • Tamamaki, N., & Nojyo, Y. (1991). Crossing fiber arrays in the rat hippocampus as demonstrated by three‐dimensional reconstruction. Journal of Comparative Neurology, 303(3), 435–442.

    Article  PubMed  CAS  Google Scholar 

  • Tang, C., & Zhang, A. (2005). Interrelated two-way clustering and its application on gene expression data. International Journal on Artificial Intelligence Tools, 14(04), 577–597.

    Article  Google Scholar 

  • Touriño, C., Ledent, C., Maldonado, R., & Valverde, O. (2008). CB1 cannabinoid receptor modulates 3, 4-methylenedioxymethamphetamine acute responses and reinforcement. Biological Psychiatry, 63(11), 1030–1038.

    Article  PubMed  CAS  Google Scholar 

  • Trevelyan, A. J., Sussillo, D., Watson, B. O., & Yuste, R. (2006). Modular propagation of epileptiform activity: evidence for an inhibitory veto in neocortex. The Journal of Neuroscience, 26(48), 12447–12455.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y., Narayanaswamy, A., Tsai, C. L., & Roysam, B. (2011). A broadly applicable 3-D neuron tracing method based on open-curve snake. Neuroinformatics, 9(2–3), 193–217.

    Article  PubMed  Google Scholar 

  • Xie, X. L., & Beni, G. (1991). A validity measure for fuzzy clustering. Pattern Analysis and Machine Intelligence, IEEE Transactions on, 13(8), 841–847.

    Article  Google Scholar 

  • Xu, X., Lu, Y., Tung, A. K., & Wang, W. (2006, April). Mining shifting-and-scaling co-regulation patterns on gene expression profiles. In Data Engineering, 2006. ICDE’06. Proceedings of the 22nd International Conference on (pp. 89–89). IEEE.

  • Xu, Y., Savelonas, M., Qiu, P., Trett, K., Shain, W., & Roysam, B. (2013, April). Unsupervised inference of arbor morphology progression for microglia from confocal microscope images. In Biomedical Imaging (ISBI), 2013 IEEE 10th International Symposium on (pp. 1356–1359). IEEE.

Download references

Information Sharing Statement

A FARSIGHT (RRID:nif-0000-10227) Wiki website provides detailed information about the open-source software system reported in this paper. The software system will be distributed as source code and installable executable for common operating systems. The website is available at: http://www.farsight-toolkit.org/wiki/Main_Page. The neuronal reconstruction datasets used in the experiments are available at: http://neuromorpho.org/neuroMorpho/index.jsp (RRID:nif-0000-00006).

Acknowledgements

This work was supported by DARPA Grant N66001-11-1-4015. We thank Audrey Cheong and Jonathan Luisi for collaborative assistance, and Sridevi Polavaram in Dr. Giorgio Ascoli’s laboratory for assistance with the L-Measure software library.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Badrinath Roysam.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lu, Y., Carin, L., Coifman, R. et al. Quantitative Arbor Analytics: Unsupervised Harmonic Co-Clustering of Populations of Brain Cell Arbors Based on L-Measure. Neuroinform 13, 47–63 (2015). https://doi.org/10.1007/s12021-014-9237-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12021-014-9237-2

Keywords

Navigation