Abstract
Electron Cryo-microscopy is an advanced imaging technique that is able to produce volumetric images of proteins that are large or hard to crystallize. De novo modeling is a process that aims at deriving the structure of the protein using the images produced by Electron Cryo-microscopy. At the medium resolutions (5 to 10Å), the location and orientation of the secondary structure elements can be computationally identified on the images. However, there is no registration between the detected secondary structure elements and the protein sequence, and therefore it is challenging to derive the atomic structure from such volume data. The skeleton of the volume image is used to interpret the connections between the secondary structure elements in order to reduce the search space of the registration problem. Unfortunately, not all features of the image can be captured using a single segmentation. Moreover, the skeleton is sensitive to the threshold used which leads to gaps in the skeleton. In this paper, we present a threshold-independent approach to overcome the problem of gaps in the skeletons. The approach uses a novel representation of the image where the image is modeled as a graph and a set of volume trees. A test containing thirteen synthesized images and two authentic images showed that our approach could improve the existent skeletons. The percent of improvement achieved were 117% and 40% for Gorgon and MapEM, respectively.
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
Chiu, W., Schmid, M.F.: Pushing back the limits of electron cryomicroscopy. Nature Structural Biology 4, 331–333 (1997)
Zhou, Z.H., Dougherty, M., Jakana, J., He, J., Rixon, F.J., Chiu, W.: Seeing the herpesvirus capsid at 8.5 A. Science 288(5467), 877–880 (2000)
Ludtke, S.J., Song, J.L., Chuang, D.T., Chiu, W.: Seeing GroEL at 6 A resolution by single particle electron cryomicroscopy. Structure 12(7), 1129–1136 (2004)
Chiu, W., Baker, M.L., Jiang, W., Zhou, Z.H.: Deriving folds of macromolecular complexes through electron cryomicroscopy and bioinformatics approaches. Current Opinion in Structural Biology 12(2), 263–269 (2002)
Conway, J.F., Cheng, N., Zlotnick, A., Wingfield, P.T., Stahl, S.J., Steven, A.C.: Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy. Nature 386(6620), 91–94 (1997)
Zhang, X., Jin, L., Fang, Q., Hui, W.H., Zhou, Z.H.: 3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry. Cell 141(3), 472–482 (2010)
Baker, M.L., Jiang, W., Wedemeyer, W.J., Rixon, F.J., Baker, D., Chiu, W.: Ab initio modeling of the herpesvirus VP26 core domain assessed by CryoEM density. PLoS Computational Biology 2(10), e146 (2006)
Martin, A.G., Depoix, F., Stohr, M., Meissner, U., Hagner-Holler, S., Hammouti, K., Burmester, T., Heyd, J., Wriggers, W., Markl, J.: Limulus polyphemus hemocyanin: 10 A cryo-EM structure, sequence analysis, molecular modelling and rigid-body fitting reveal the interfaces between the eight hexamers. Journal of Molecular Biology 366(4), 1332–1350 (2007)
Villa, E., Sengupta, J., Trabuco, L.G., LeBarron, J., Baxter, W.T., Shaikh, T.R., Grassucci, R.A., Nissen, P., Ehrenberg, M., Schulten, K., Frank, J.: Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis. Proceedings of the National Academy of Sciences of the United States of America (PNAS) 106(4), 1063–1068 (2009)
Lasker, K., Dror, O., Shatsky, M., Nussinov, R., Wolfson, H.J.: EMatch: discovery of high resolution structural homologues of protein domains in intermediate resolution cryo-EM maps. IEEE/ACM Transactions on Computational Biology and Bioinformatics 4(1), 28–39 (2007)
Jiang, W., Baker, M.L., Ludtke, S.J., Chiu, W.: Bridging the information gap: computational tools for intermediate resolution structure interpretation. Journal of Molecular Biology 308(5), 1033–1044 (2001)
Del Palu, A., He, J., Pontelli, E., Lu, Y.: Identification of Alpha-Helices from Low Resolution Protein Density Maps. In: Proceeding of Computational Systems Bioinformatics Conference (CSB), pp. 89–98 (2006)
Baker, M.L., Ju, T., Chiu, W.: Identification of secondary structure elements in intermediate-resolution density maps. Structure 15(1), 7–19 (2007)
Si, D., Ji, S., Al Nasr, K., He, J.: A machine learning approach for the identification of protein secondary structure elements from cryoEM density maps. Biopolymers 97, 698–708 (2012)
Jones, D.T.: Protein secondary structure prediction based on position-specific scoring matrices. Journal of Molecular Biology 292(2), 195–202 (1999)
Pollastri, G., McLysaght, A.: Porter: a new, accurate server for protein secondary structure prediction. Bioinformatics 21(8), 1719–1720 (2005)
Al Nasr, K., Ranjan, D., Zubair, M., He, J.: Ranking Valid Topologies of the Secondary Structure elements Using a constraint Graph. Journal of Bioinformatics and Computational Biology 9(3), 415–430 (2011)
Al Nasr, K., Sun, W., He, J.: Structure prediction for the helical skeletons detected from the low resolution protein density map. BMC Bioinformatics 11(suppl. 1), S44 (2010)
Lindert, S., Staritzbichler, R., Wötzel, N., Karakaş, M., Stewart, P.L., Meiler, J.: EM-Fold: De Novo Folding of α-Helical Proteins Guided by Intermediate-Resolution Electron Microscopy Density Maps. Structure 17(7), 990–1003 (2009)
Lindert, S., Alexander, N., Wötzel, N., Karaka, M., Stewart, P.L., Meiler, J.: EM-Fold: De Novo Atomic-Detail Protein Structure Determination from Medium-Resolution Density Maps. Structure 20(3), 464–478 (2012)
Al Nasr, K., Chen, L., Si, D., Ranjan, D., Zubair, M., He, J.: Building the initial chain of the proteins through de novo modeling of the cryo-electron microscopy volume data at the medium resolutions. In: Proceedings of the ACM Conference on Bioinformatics, Computational Biology and Biomedicine, Orlando, Florida, pp. 490–497 (2012)
Khromov, D., Mestetskiy, L.: 3D Skeletonization as an Optimization Problem. In: The Canadian Conference on Computational Geometry, Charlottetown, pp. 259–264 (2012)
Dey, T.K., Zhao, W.: Approximate medial axis as a voronoi subcomplex. In: Proceedings of the Seventh ACM Symposium on Solid Modeling and Applications, Saarbrücken, Germany, pp. 356–366 (2002)
Foskey, M., Lin, M.C., Manocha, D.: Efficient Computation of A Simplified Medial Axis. Journal of Computing and Information Science in Engineering 3(4), 274–284 (2003)
Tam, R., Heidrich, W.: Shape simplification based on the medial axis transform, pp. 481–488
Tran, S., Shih, L.: Efficient 3D binary image skeletonization, pp. 364–372
She, F.H., Chen, R.H., Gao, W.M., Hodgson, P.H., Kong, L.X., Hong, H.Y.: Improved 3D Thinning Algorithms for Skeleton Extraction, pp. 14–18
van Dortmont, M.A.M.M., van de Wetering, H.M.M., Telea, A.C.: Skeletonization and distance transforms of 3D volumes using graphics hardware. In: Kuba, A., Nyúl, L.G., Palágyi, K. (eds.) DGCI 2006. LNCS, vol. 4245, pp. 617–629. Springer, Heidelberg (2006)
Ju, T., Baker, M.L., Chiu, W.: Computing a family of skeletons of volumetric models for shape description. Computer-Aided Design 39(5), 352–360 (2007)
Abeysinghe, S.S., Baker, M., Wah, C., Tao, J.: Segmentation-free skeletonization of grayscale volumes for shape understanding, pp. 63–71
Abeysinghe, S.S., Ju, T.: Interactive skeletonization of intensity volumes. Vis. Comput. 25(5-7), 627–635 (2009)
Kong, Y., Zhang, X., Baker, T.S., Ma, J.: A Structural-informatics approach for tracing beta-sheets: building pseudo-C(alpha) traces for beta-strands in intermediate-resolution density maps. Journal of Molecular Biology 339(1), 117–130 (2004)
Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E.: UCSF Chimera—A visualization system for exploratory research and analysis. Journal of Computational Chemistry 25(13), 1605–1612 (2004)
Baker, M.L., Abeysinghe, S.S., Schuh, S., Coleman, R.A., Abrams, A., Marsh, M.P., Hryc, C.F., Ruths, T., Chiu, W., Ju, T.: Modeling protein structure at near atomic resolutions with Gorgon. Journal of Structural Biology 174(2), 360–373 (2011)
Al Nasr, K.: De novo protein structure modeling from cryoem data through a dynamic programming algorithm in the secondary structure topology graph. Dissertation, Department of Computer Science, Old Dominion University (2012)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Nasr, K.A., Liu, C., Rwebangira, M.R., Burge, L.L.I. (2013). A Graph Approach to Bridge the Gaps in Volumetric Electron Cryo-microscopy Skeletons. In: Cai, Z., Eulenstein, O., Janies, D., Schwartz, D. (eds) Bioinformatics Research and Applications. ISBRA 2013. Lecture Notes in Computer Science(), vol 7875. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38036-5_22
Download citation
DOI: https://doi.org/10.1007/978-3-642-38036-5_22
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-38035-8
Online ISBN: 978-3-642-38036-5
eBook Packages: Computer ScienceComputer Science (R0)