Skip to content
naulon

No retraction, correction or concern found when last checked on Nov 1, 2026.

NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases

Marta Costa, James D. Manton, Aaron D. Ostrovsky and 2 more

Neuron · 2016 · CC BY

doi:10.1101/006346

Abstract

Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish.

References 78

  1. 1.

    Altschul S.F., Gish W., Miller W., Myers E.W., Lipman D.J. Basic local alignment search tool. J. Mol. Biol. 1990;215:403-410.

    Not in our library10.1016/s0022-2836(05)80360-2

  2. 2.

    Armañanzas R., Ascoli G.A. Towards the automatic classification of neurons. Trends Neurosci. 2015;38:307-318.

    Not in our library10.1016/j.tins.2015.02.004

  3. 3.

    Ascoli G.A., Alonso-Nanclares L., Anderson S.A., Barrionuevo G., Benavides-Piccione R., Burkhalter A., Buzsáki G., Cauli B., Defelipe J., Fairén A., Petilla Interneuron Nomenclature Group. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci. 2008;9:557-568.

    Not in our library10.1038/nrn2402

  4. 4.

    Aso Y., Grübel K., Busch S., Friedrich A.B., Siwanowicz I., Tanimoto H. The mushroom body of adult Drosophila characterized by GAL4 drivers. J. Neurogenet. 2009;23:156-172.

    Not in our library10.1080/01677060802471718

  5. 5.
  6. 6.

    Badea T.C., Nathans J. Quantitative analysis of neuronal morphologies in the mouse retina visualized by using a genetically directed reporter. J. Comp. Neurol. 2004;480:331-351.

    Not in our library10.1002/cne.20304

  7. 7.

    Ballard D.H. Generalizing the Hough transform to detect arbitrary shapes. Pattern Recognit. 1981;13:111-122.

    Not in our library

  8. 8.

    Basu, S., Condron, B., and Acton, S.T. (2011). Path2Path: hierarchical path-based analysis for neuron matching. In Biomedical Imaging: From Nano to Macro, 2011 IEEE International Symposium on Biomedical Imaging (IEEE), pp. 996–999.

    Not in our library

  9. 9.

    Bodenhofer U., Kothmeier A., Hochreiter S. APCluster: an R package for affinity propagation clustering. Bioinformatics. 2011;27:2463-2464.

    Not in our library10.1093/bioinformatics/btr406

  10. 10.

    Bota M., Swanson L.W. The neuron classification problem. Brain Res. Brain Res. Rev. 2007;56:79-88.

    Not in our library10.1016/j.brainresrev.2007.05.005

  11. 11.
  12. 12.

    Cajal S.R. Histologie du Système Nerveux de l’Homme et des Vertébrés. 1911.

    Not in our library

  13. 13.

    Cardona A., Saalfeld S., Arganda I., Pereanu W., Schindelin J., Hartenstein V. Identifying neuronal lineages of Drosophila by sequence analysis of axon tracts. J. Neurosci. 2010;30:7538-7553.

    Not in our library10.1523/jneurosci.0186-10.2010

  14. 14.

    Chiang A.S., Lin C.Y., Chuang C.C., Chang H.M., Hsieh C.H., Yeh C.W., Shih C.T., Wu J.J., Wang G.T., Chen Y.C. Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution. Curr. Biol. 2011;21:1-11.

    Not in our library10.1016/j.cub.2010.11.056

  15. 15.

    Doube M., Kłosowski M.M., Arganda-Carreras I., Cordelières F.P., Dougherty R.P., Jackson J.S., Schmid B., Hutchinson J.R., Shefelbine S.J. BoneJ: free and extensible bone image analysis in ImageJ. Bone. 2010;47:1076-1079.

    Not in our library10.1016/j.bone.2010.08.023

  16. 16.

    El Jundi B., Heinze S., Lenschow C., Kurylas A., Rohlfing T., Homberg U. The locust standard brain: a 3D standard of the central complex as a platform for neural network analysis. Front. Syst. Neurosci. 2010;3:21.

    Not in our library10.3389/neuro.06.021.2009

  17. 17.

    Elseberg J., Magnenat S., Siegwart R., Nüchter A. Comparison of nearest-neighbor-search strategies and implementations for efficient shape registration. Journal of Software Engineering for Robotics. 2012;3:2-12.

    Not in our library

  18. 18.

    Fischbach K.F., Dittrich A. The optic lobe of Drosophila melanogaster. I. A Golgi analysis of wild-type structure. Cell Tissue Res. 1989;258:441-475.

    Not in our library

  19. 19.

    Frey B.J., Dueck D. Clustering by passing messages between data points. Science. 2007;315:972-976.

    Not in our library10.1126/science.1136800

  20. 20.

    Ganglberger F., Schulze F., Tirian L., Novikov A., Dickson B., Bühler K., Langs G. Structure-based neuron retrieval across Drosophila brains. Neuroinformatics. 2014;12:423-434.

    Not in our library10.1007/s12021-014-9219-4

  21. 21.

    Heinze S., Florman J., Asokaraj S., El Jundi B., Reppert S.M. Anatomical basis of sun compass navigation II: the neuronal composition of the central complex of the monarch butterfly. J. Comp. Neurol. 2013;521:267-298.

    Not in our library10.1002/cne.23214

  22. 22.

    Ito K., Shinomiya K., Ito M., Armstrong J.D., Boyan G., Hartenstein V., Harzsch S., Heisenberg M., Homberg U., Jenett A., Insect Brain Name Working Group. A systematic nomenclature for the insect brain. Neuron. 2014;81:755-765.

    Not in our library10.1016/j.neuron.2013.12.017

  23. 23.

    Jefferis G.S.X.E., Livet J. Sparse and combinatorial neuron labelling. Curr. Opin. Neurobiol. 2012;22:101-110.

    Not in our library10.1016/j.conb.2011.09.010

  24. 24.

    Jefferis G.S.X.E., Manton J.D. NeuroAnatomy Toolbox v1.5.2. Zenodo. 2014.

    Not in our library

  25. 25.

    Jefferis G.S., Marin E.C., Stocker R.F., Luo L. Target neuron prespecification in the olfactory map of Drosophila. Nature. 2001;414:204-208.

    Not in our library10.1038/35102574

  26. 26.
  27. 27.

    Jenett A., Rubin G.M., Ngo T.T., Shepherd D., Murphy C., Dionne H., Pfeiffer B.D., Cavallaro A., Hall D., Jeter J. A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012;2:991-1001.

    Not in our library10.1016/j.celrep.2012.09.011

  28. 28.

    Kahsai L., Zars T. Learning and memory in Drosophila: behavior, genetics, and neural systems. Int. Rev. Neurobiol. 2011;99:139-167.

    Not in our library10.1016/b978-0-12-387003-2.00006-9

  29. 29.
  30. 30.

    Kamikouchi A., Shimada T., Ito K. Comprehensive classification of the auditory sensory projections in the brain of the fruit fly Drosophila melanogaster. J. Comp. Neurol. 2006;499:317-356.

    Not in our library10.1002/cne.21075

  31. 31.

    Kamikouchi A., Inagaki H.K., Effertz T., Hendrich O., Fiala A., Göpfert M.C., Ito K. The neural basis of Drosophila gravity-sensing and hearing. Nature. 2009;458:165-171.

    Not in our library10.1038/nature07810

  32. 32.

    Karlin S., Altschul S.F. Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. Proc. Natl. Acad. Sci. USA. 1990;87:2264-2268.

    Not in our library10.1073/pnas.87.6.2264

  33. 33.

    Kepecs A., Fishell G. Interneuron cell types are fit to function. Nature. 2014;505:318-326.

    Not in our library10.1038/nature12983

  34. 34.

    Khoshelham, K. (2007). Extending generalized hough transform to detect 3D objects in laser range data. In ISPRS Workshop on Laser Scanning, ISPRS Proceedings (ISPRS), pp. 206–210.

    Not in our library

  35. 35.

    Kimura K., Ote M., Tazawa T., Yamamoto D. Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain. Nature. 2005;438:229-233.

    Not in our library10.1038/nature04229

  36. 36.

    Kimura K., Hachiya T., Koganezawa M., Tazawa T., Yamamoto D. Fruitless and doublesex coordinate to generate male-specific neurons that can initiate courtship. Neuron. 2008;59:759-769.

    Not in our library10.1016/j.neuron.2008.06.007

  37. 37.

    Koganezawa M., Haba D., Matsuo T., Yamamoto D. The shaping of male courtship posture by lateralized gustatory inputs to male-specific interneurons. Curr. Biol. 2010;20:1-8.

    Not in our library10.1016/j.cub.2009.11.038

  38. 38.

    Kong J.H., Fish D.R., Rockhill R.L., Masland R.H. Diversity of ganglion cells in the mouse retina: unsupervised morphological classification and its limits. J. Comp. Neurol. 2005;489:293-310.

    Not in our library10.1002/cne.20631

  39. 39.

    Lai J.S.Y., Lo S.J., Dickson B.J., Chiang A.S. Auditory circuit in the Drosophila brain. Proc. Natl. Acad. Sci. USA. 2012;109:2607-2612.

    Not in our library10.1073/pnas.1117307109

  40. 40.

    Lee T.C., Kashyap R.L., Chu C.N. Building skeleton models via 3-D medial surface/axis thinning algorithms. CVGIP Graph. Models Image Process. 1994;56:462-478.

    Not in our library

  41. 41.

    Lee T., Lee A., Luo L. Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast. Development. 1999;126:4065-4076.

    Not in our library10.1242/dev.126.18.4065

  42. 42.

    Lein E.S., Hawrylycz M.J., Ao N., Ayres M., Bensinger A., Bernard A., Boe A.F., Boguski M.S., Brockway K.S., Byrnes E.J. Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2007;445:168-176.

    Not in our library10.1038/nature05453

  43. 43.

    Lin H.H., Lai J.S.Y., Chin A.L., Chen Y.C., Chiang A.S. A map of olfactory representation in the Drosophila mushroom body. Cell. 2007;128:1205-1217.

    Not in our library10.1016/j.cell.2007.03.006

  44. 44.

    Lin C.Y., Chuang C.C., Hua T.E., Chen C.C., Dickson B.J., Greenspan R.J., Chiang A.S. A comprehensive wiring diagram of the protocerebral bridge for visual information processing in the Drosophila brain. Cell Rep. 2013;3:1739-1753.

    Not in our library10.1016/j.celrep.2013.04.022

  45. 45.

    Luan H., Peabody N.C., Vinson C.R., White B.H. Refined spatial manipulation of neuronal function by combinatorial restriction of transgene expression. Neuron. 2006;52:425-436.

    Not in our library10.1016/j.neuron.2006.08.028

  46. 46.

    Manton J.D., Ostrovsky A.D., Goetz L., Costa M., Rohlfing T., Jefferis G.S.X.E. Combining genome-scale Drosophila 3D neuroanatomical data by bridging template brains. bioRxiv. 2014.

    Not in our library

  47. 47.

    Marin E.C., Jefferis G.S., Komiyama T., Zhu H., Luo L. Representation of the glomerular olfactory map in the Drosophila brain. Cell. 2002;109:243-255.

    Not in our library10.1016/s0092-8674(02)00700-6

  48. 48.

    Masse N.Y., Turner G.C., Jefferis G.S.X.E. Olfactory information processing in Drosophila. Curr. Biol. 2009;19:R700-R713.

    Not in our library10.1016/j.cub.2009.06.026

  49. 49.

    Masse N.Y., Cachero S., Ostrovsky A.D., Jefferis G.S.X.E. A mutual information approach to automate identification of neuronal clusters in Drosophila brain images. Front. Neuroinform. 2012;6:21.

    Not in our library10.3389/fninf.2012.00021

  50. 50.

    Matsuo E., Seki H., Asai T., Morimoto T., Miyakawa H., Ito K., Kamikouchi A. Organization of projection neurons and local neurons of the primary auditory center in the fruit fly Drosophila melanogaster. J. Comp. Neurol. 2016;524:1099-1164.

    Not in our library10.1002/cne.23955

  51. 51.

    Mayerich D., Bjornsson C., Taylor J., Roysam B. NetMets: software for quantifying and visualizing errors in biological network segmentation. BMC Bioinformatics. 2012;13(Suppl 8):S7.

    Not in our library10.1186/1471-2105-13-s8-s7

  52. 52.

    Migliore M., Shepherd G.M. Opinion: an integrated approach to classifying neuronal phenotypes. Nat. Rev. Neurosci. 2005;6:810-818.

    Not in our library10.1038/nrn1769

  53. 53.

    Miyasaka N., Arganda-Carreras I., Wakisaka N., Masuda M., Sümbül U., Seung H.S., Yoshihara Y. Olfactory projectome in the zebrafish forebrain revealed by genetic single-neuron labelling. Nat. Commun. 2014;5:3639.

    Not in our library10.1038/ncomms4639

  54. 54.

    Morante J., Desplan C. The color-vision circuit in the medulla of Drosophila. Curr. Biol. 2008;18:553-565.

    Not in our library10.1016/j.cub.2008.02.075

  55. 55.

    Nelson S.B., Sugino K., Hempel C.M. The problem of neuronal cell types: a physiological genomics approach. Trends Neurosci. 2006;29:339-345.

    Not in our library10.1016/j.tins.2006.05.004

  56. 56.

    Oh S.W., Harris J.A., Ng L., Winslow B., Cain N., Mihalas S., Wang Q., Lau C., Kuan L., Henry A.M. A mesoscale connectome of the mouse brain. Nature. 2014;508:207-214.

    Not in our library10.1038/nature13186

  57. 57.

    Ohyama T., Schneider-Mizell C.M., Fetter R.D., Aleman J.V., Franconville R., Rivera-Alba M., Mensh B.D., Branson K.M., Simpson J.H., Truman J.W. A multilevel multimodal circuit enhances action selection in Drosophila. Nature. 2015;520:633-639.

    Not in our library10.1038/nature14297

  58. 58.

    Otsuna H., Ito K. Systematic analysis of the visual projection neurons of Drosophila melanogaster. I. Lobula-specific pathways. J. Comp. Neurol. 2006;497:928-958.

    Not in our library10.1002/cne.21015

  59. 59.

    Parekh R., Ascoli G.A. Neuronal morphology goes digital: a research hub for cellular and system neuroscience. Neuron. 2013;77:1017-1038.

    Not in our library10.1016/j.neuron.2013.03.008

  60. 60.

    Peng H., Tang J., Xiao H., Bria A., Zhou J., Butler V., Zhou Z., Gonzalez-Bellido P.T., Oh S.W., Chen J. Virtual finger boosts three-dimensional imaging and microsurgery as well as terabyte volume image visualization and analysis. Nat. Commun. 2014;5:4342.

    Not in our library10.1038/ncomms5342

  61. 61.

    Peng H., Hawrylycz M., Roskams J., Hill S., Spruston N., Meijering E., Ascoli G.A. BigNeuron: large-scale 3D neuron reconstruction from optical microscopy images. Neuron. 2015;87:252-256.

    Not in our library10.1016/j.neuron.2015.06.036

  62. 62.

    Rohlfing T., Maurer C.R.J. Nonrigid image registration in shared-memory multiprocessor environments with application to brains, breasts, and bees. IEEE Trans. Inf. Technol. Biomed. 2003;7:16-25.

    Not in our library10.1109/titb.2003.808506

  63. 63.

    Rowe M.H., Stone J. Naming of neurones. Classification and naming of cat retinal ganglion cells. Brain Behav. Evol. 1977;14:185-216.

    Not in our library10.1159/000125660

  64. 64.
  65. 65.

    Schindelin J., Arganda-Carreras I., Frise E., Kaynig V., Longair M., Pietzsch T., Preibisch S., Rueden C., Saalfeld S., Schmid B. Fiji: an open-source platform for biological-image analysis. Nat. Methods. 2012;9:676-682.

    Not in our library10.1038/nmeth.2019

  66. 66.

    Sümbül U., Song S., McCulloch K., Becker M., Lin B., Sanes J.R., Masland R.H., Seung H.S. A genetic and computational approach to structurally classify neuronal types. Nat. Commun. 2014;5:3512.

    Not in our library10.1038/ncomms4512

  67. 67.

    Sunkin S.M., Ng L., Lau C., Dolbeare T., Gilbert T.L., Thompson C.L., Hawrylycz M., Dang C. Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system. Nucleic Acids Res. 2013;41:D996-D1008.

    Not in our library10.1093/nar/gks1042

  68. 68.

    Susaki E.A., Tainaka K., Perrin D., Kishino F., Tawara T., Watanabe T.M., Yokoyama C., Onoe H., Eguchi M., Yamaguchi S. Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell. 2014;157:726-739.

    Not in our library10.1016/j.cell.2014.03.042

  69. 69.

    Suzek B.E., Huang H., McGarvey P., Mazumder R., Wu C.H. UniRef: comprehensive and non-redundant UniProt reference clusters. Bioinformatics. 2007;23:1282-1288.

    Not in our library10.1093/bioinformatics/btm098

  70. 70.

    Tanaka N.K., Tanimoto H., Ito K. Neuronal assemblies of the Drosophila mushroom body. J. Comp. Neurol. 2008;508:711-755.

    Not in our library10.1002/cne.21692

  71. 71.

    Tanaka N.K., Endo K., Ito K. Organization of antennal lobe-associated neurons in adult Drosophila melanogaster brain. J. Comp. Neurol. 2012;520:4067-4130.

    Not in our library10.1002/cne.23142

  72. 72.

    Wan Y., Long F., Qu L., Xiao H., Hawrylycz M., Myers E.W., Peng H. BlastNeuron for automated comparison, retrieval and clustering of 3D neuron morphologies. Neuroinformatics. 2015;13:487-499.

    Not in our library10.1007/s12021-015-9272-7

  73. 73.

    Wong A.M., Wang J.W., Axel R. Spatial representation of the glomerular map in the Drosophila protocerebrum. Cell. 2002;109:229-241.

    Not in our library10.1016/s0092-8674(02)00707-9

  74. 74.

    Yorozu S., Wong A., Fischer B.J., Dankert H., Kernan M.J., Kamikouchi A., Ito K., Anderson D.J. Distinct sensory representations of wind and near-field sound in the Drosophila brain. Nature. 2009;458:201-205.

    Not in our library10.1038/nature07843

  75. 75.
  76. 76.

    Yu J.Y., Kanai M.I., Demir E., Jefferis G.S.X.E., Dickson B.J. Cellular organization of the neural circuit that drives Drosophila courtship behavior. Curr. Biol. 2010;20:1602-1614.

    Not in our library10.1016/j.cub.2010.08.025

  77. 77.

    Zhu S., Chiang A.S., Lee T. Development of the Drosophila mushroom bodies: elaboration, remodeling and spatial organization of dendrites in the calyx. Development. 2003;130:2603-2610.

    Not in our library10.1242/dev.00466

  78. 78.

    Zingg B., Hintiryan H., Gou L., Song M.Y., Bay M., Bienkowski M.S., Foster N.N., Yamashita S., Bowman I., Toga A.W., Dong H.W. Neural networks of the mouse neocortex. Cell. 2014;156:1096-1111.

    Not in our library10.1016/j.cell.2014.02.023

Cited by papers we hold 14

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.