Abstract
Electron tomography is the most widely applicable method for obtaining 3D information by electron microscopy. In the field of biology it has been realized that electron tomography is capable of providing a complete, molecular resolution three-dimensional mapping of entire proteoms. However, to realize this goal, information needs to be extracted efficiently from these tomograms. Owing to extremely low signal-to-noise ratios, this task is mostly carried out manually. Standard template matching approaches tend to generate large amounts of false positives. We developed an alternative method for feature extraction in biological electron tomography based on reduced representation templates, approximating the search model by a small number of anchor points used to calculate the scoring function. Using this approach we see a reduction of about 50% false positives with matched-filter approaches to below 5%. At the same time, false negatives stay below 5%, thus essentially matching the performance one would expect from human operators.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Frey, T.G., Perkins, G.A., Ellisman, M.H.: Electron Tomography of Membrane-Bound Cellular Organelles. Annu. Rev. Biophys. Biomol. Struct. 35, 199–224 (2006)
Subramaniam, S.: Bridging the imaging gap: visualizing subcellular architecture with electron tomography. Curr. Opin. Microbiol. 8, 316–322 (2005)
McIntosh, R., Nicastro, D., Mastronarde, D.: New views of cells in 3D: an introduction to electron tomography. Trends. Cell. Biol. 15, 43–51 (2005)
Lucic, V., Yang, T., Schweikert, G., Forster, F., Baumeister, W.: Morphological characterization of molecular complexes present in the synaptic cleft. Structure 13, 423–434 (2005)
Leis, A.P., Beck, M., Gruska, M., Best, C., Hegerl, R., Baumeister, W., Leis, J.W.: Cryo-electron tomography of biological specimens. IEEE Signal. Proc. Mag. 23, 95–103 (2006)
Sali, A., Glaeser, R., Earnest, T., Baumeister, W.: From words to literature in structural proteomics. Nature 422, 216–225 (2003)
Nickell, S., Kofler, C., Leis, A.P., Baumeister, W.: A visual approach to proteomics. Nat. Rev. Mol. Cell. Biol. 7, 225–230 (2006)
Baumeister, W.: From proteomic inventory to architecture. FEBS Lett. 579, 933–937 (2005)
Marsh, B.J., Mastronarde, D.N., Buttle, K.F., Howell, K.E., McIntosh, J.R.: Organellar relationships in the Golgi region of the pancreatic beta cell line, HIT-T15, visualized by high resolution electron tomography. Proc. Natl. Acad. Sci. USA 98, 2399–2406 (2001)
Iancu, C.V., Wright, E.R., Heymann, J.B., Jensen, G.J.: A comparison of liquid nitrogen and liquid helium as cryogens for electron cryotomography. J. Struct. Biol. 153, 231–240 (2006)
McEwen, B.F., Downing, K.H., Glaeser, R.M.: The relevance of dose-fractionation in tomography of radiation-sensitive specimens. Ultramicroscopy 60, 357–373 (1995)
Al-Amoudi, A., Norlen, L.P., Dubochet, J.: Cryo-electron microscopy of vitreous sections of native biological cells and tissues. J. Struct. Biol. 148, 131–135 (2004)
McEwen, B.F., Marko, M.: The emergence of electron tomography as an important tool for investigating cellular ultrastructure. J. Histochem. Cytochem. 49, 553–564 (2001)
Marsh, B.J.: Lessons from tomographic studies of the mammalian Golgi. Biochim. Biophys. Acta. 1744, 273–292 (2005)
Frangakis, A.S., Förster, F.: Computational exploration of structural information from cryo-electron tomograms. Curr. Opin. Struct. Biol. 14, 325–331 (2004)
Sandberg, K., Brega, M.: Segmentation of thin structures in electron micrographs using orientation fields. J. Struct. Biol. 157, 403–415 (2007)
Volkmann, N.: Methods for segmentation and interpretation of electron tomographic reconstructions. Methods. Enzymol. 483, 31–46 (2010)
Volkmann, N.: Putting structure into context: fitting of atomic models into electron microscopic and electron tomographic reconstructions. Curr. Opin. Cell. Biol. 24, 141–147 (2012)
Böhm, J., Frangakis, A.S., Hegerl, R., Nickell, S., Typke, D., Baumeister, W.: From the cover: toward detecting and identifying macromolecules in a cellular context: template matching applied to electron tomograms. Proc. Natl. Acad. Sci. USA 97, 14245–14250 (2000)
Frangakis, A.S., Hegerl, R.: Segmentation of two- and three-dimensional data from electron microscopy using eigenvector analysis. J. Struct. Biol. 138, 105–113 (2002)
Ortiz, J.O., Forster, F., Kurner, J., Linaroudis, A.A., Baumeister, W.: Mapping 70S ribosomes in intact cells by cryoelectron tomography and pattern recognition. J. Struct. Biol. 156, 334–341 (2006)
Rath, B.K., Hegerl, R., Leith, A., Shaikh, T.R., Wagenknecht, T., Frank, J.: Fast 3D motif search of EM density maps using a locally normalized cross-correlation function. J. Struct. Biol. 144, 95–103 (2003)
Sigworth, F.J.: Classical detection theory and the cryo-EM particle selection problem. J. Struct. Biol. 145, 111–122 (2004)
van der Heide, P., Xu, X.P., Marsh, B.J., Hanein, D., Volkmann, N.: Efficient automatic noise reduction of electron tomographic reconstructions based on iterative median filtering. J. Struct. Biol. 158, 196–204 (2007)
Spahn, C.M., Jan, E., Mulder, A., Grassucci, R.A., Sarnow, P., Frank, J.: Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: the IRES functions as an RNA-based translation factor. Cell 118, 465–475 (2004)
Volkmann, N.: An approach to automated particle picking from electron micrographs based on reduced representation templates. J. Struct. Biol. 145, 152–156 (2004)
Volkmann, N.: A novel three-dimensional variant of the watershed transform for segmentation of electron density maps. J. Struct. Biol. 138, 123–129 (2002)
Rouiller, I., Xu, X.P., Amann, K.J., Egile, C., Nickell, S., Nicastro, D., Li, R., Pollard, T.D., Volkmann, N., Hanein, D.: The structural basis of actin filament branching by Arp2/3 complex. J. Cell. Biol. 180, 887–895 (2008)
Janssen, M.E., Kim, E., Liu, H., Fujimoto, L.M., Bobkov, A., Volkmann, N., Hanein, D.: Three-dimensional structure of vinculin bound to actin filaments. Mol. Cell 21, 271–281 (2006)
Zhu, Y., Carragher, B., Glaeser, R.M., Fellmann, D., Bajaj, C., Bern, M., Mouche, F., de Haas, F., Hall, R.J., Kriegman, D.J., Ludtke, S.J., Mallick, S.P., Penczek, P.A., Roseman, A.M., Sigworth, F.J., Volkmann, N., Potter, C.S.: Automatic particle selection: results of a comparative study. J. Struct. Biol. 145, 3–14 (2004)
Pollard, T.D., Borisy, G.G.: Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this paper
Cite this paper
Xu, XP., Page, C., Volkmann, N. (2015). Efficient Extraction of Macromolecular Complexes from Electron Tomograms Based on Reduced Representation Templates. In: Azzopardi, G., Petkov, N. (eds) Computer Analysis of Images and Patterns. CAIP 2015. Lecture Notes in Computer Science(), vol 9256. Springer, Cham. https://doi.org/10.1007/978-3-319-23192-1_35
Download citation
DOI: https://doi.org/10.1007/978-3-319-23192-1_35
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-23191-4
Online ISBN: 978-3-319-23192-1
eBook Packages: Computer ScienceComputer Science (R0)