The Community for Technology Leaders
RSS Icon
Subscribe
Issue No.05 - Sept.-Oct. (2013 vol.10)
pp: 1289-1298
Kamal Al Nasr , Dept. of Comput. Sci., Tennessee State Univ., Nashville, TN, USA
Chunmei Liu , Dept. of Syst. & Comput. Sci., Howard Univ., Washington, DC, USA
Mugizi Rwebangira , Dept. of Syst. & Comput. Sci., Howard Univ., Washington, DC, USA
Legand Burge , Dept. of Syst. & Comput. Sci., Howard Univ., Washington, DC, USA
Jing He , Dept. of Comput. Sci., Old Dominion Univ., Norfolk, VA, USA
ABSTRACT
Cryo-electron microscopy is an experimental technique that is able to produce 3D gray-scale images of protein molecules. In contrast to other experimental techniques, cryo-electron microscopy is capable of visualizing large molecular complexes such as viruses and ribosomes. At medium resolution, the positions of the atoms are not visible and the process cannot proceed. The medium-resolution images produced by cryo-electron microscopy are used to derive the atomic structure of the proteins in de novo modeling. The skeletons of the 3D gray-scale images are used to interpret important information that is helpful in de novo modeling. Unfortunately, not all features of the image can be captured using a single segmentation. In this paper, we present a segmentation-free approach to extract the gray-scale curve-like skeletons. The approach relies on a novel representation of the 3D image, where the image is modeled as a graph and a set of volume trees. A test containing 36 synthesized maps and one authentic map shows that our approach can improve the performance of the two tested tools used in de novo modeling. The improvements were 62 and 13 percent for Gorgon and DP-TOSS, respectively.
INDEX TERMS
Skeleton, Proteins, Gray-scale, Algorithm design and analysis, Solid modeling, Microscopy,volumetric image representation, Image processing, graphs, modeling techniques
CITATION
Kamal Al Nasr, Chunmei Liu, Mugizi Rwebangira, Legand Burge, Jing He, "Intensity-Based Skeletonization of CryoEM Gray-Scale Images Using a True Segmentation-Free Algorithm", IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol.10, no. 5, pp. 1289-1298, Sept.-Oct. 2013, doi:10.1109/TCBB.2013.121
REFERENCES
[1] E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng, and T.E. Ferrin, "UCSF Chimera—A Visualization System for Exploratory Research and Analysis," J. Computational Chemistry, vol. 25, no. 13, pp. 1605-1612, 2004.
[2] D. Khromov and L. Mestetskiy, "3D Skeletonization as an Optimization Problem," Proc. Canadian Conf. Computational Geometry, pp. 259-264, 2012.
[3] T.K. Dey and W. Zhao, "Approximate Medial Axis as a Voronoi Subcomplex," Proc. Seventh ACM Symp. Solid Modeling and Applications, pp. 356-366, 2002.
[4] M. Foskey, M.C. Lin, and D. Manocha, "Efficient Computation of a Simplified Medial Axis," J. Computing and Information Science in Eng., vol. 3, no. 4, pp. 274-284, 2003.
[5] R. Tam and W. Heidrich, "Shape Simplification Based on the Medial Axis Transform," Proc. IEEE Visualization, pp. 481-488, 2003.
[6] S. Tran and L. Shih, "Efficient 3D Binary Image Skeletonization," Proc. IEEE Computational Systems Bioinformatics Conf. Workshops and Poster Abstracts, pp. 364-372, 2005.
[7] F.H. She, R.H. Chen, W.M. Gao, P.H. Hodgson, L.X. Kong, and H.Y. Hong, "Improved 3D Thinning Algorithms for Skeleton Extraction," Proc. Digital Image Computing: Techniques and Applications, pp. 14-18, 2009.
[8] M.A.M.M.v. Dortmont, H.M.M.v.d. Wetering, and A.C. Telea, "Skeletonization and Distance Transforms of 3D Volumes Using Graphics Hardware," Proc. 13th Int'l Conf. Discrete Geometry for Computer Imagery, pp. 617-629, 2006.
[9] B. Xiang, L.J. Latecki, and L. Wen-Yu, "Skeleton Pruning by Contour Partitioning with Discrete Curve Evolution," IEEE Trans. Pattern Analysis and Machine Intelligence, vol. 29, no. 3, pp. 449-462, Mar. 2007.
[10] W. Xie, R.P. Thompson, and R. Perucchio, "A Topology-Preserving Parallel 3D Thinning Algorithm for Extracting the Curve Skeleton," Pattern Recognition, vol. 36, no. 7, pp. 1529-1544, July 2003.
[11] F. Leymarie and M.D. Levine, "Simulating the Grassfire Transform Using an Active Contour Model," IEEE Trans. Pattern Analysis and Machine Intelligence, vol. 14, no. 1, pp. 56-75, Jan. 1992.
[12] K. Palagyi and A. Kuba, "Directional 3D Thinning Using 8 Subiterations," Proc. Eighth Int'l Conf. Discrete Geometry for Computer Imagery, pp. 325-336, 1999.
[13] T. Ju, M.L. Baker, and W. Chiu, "Computing a Family of Skeletons of Volumetric Models for Shape Description," Computer-Aided Design, vol. 39, no. 5, pp. 352-360, May 2007.
[14] N. Mayya and V.T. Rajan, "Voronoi Diagrams of Polygons: A Framework for Shape Representation," J. Math. Imaging and Vision, vol. 6, no. 4, pp. 355-378, Dec. 1996.
[15] J.W. Brandt and V.R. Algazi, "Continuous Skeleton Computation by Voronoi Diagram," CVGIP: Image Understanding, vol. 55, no. 3, pp. 329-338, May 1992.
[16] T.K. Dey and W. Zhao, "Approximate Medial Axis as a Voronoi Subcomplex," Computer-Aided Design, vol. 36, no. 2, pp. 195-202, Feb. 2004.
[17] W.-P. Choi, K.-M. Lam, and W.-C. Siu, "Extraction of the Euclidean Skeleton Based on a Connectivity Criterion," Pattern Recognition, vol. 36, no. 3, pp. 721-729, Mar. 2003.
[18] P. Golland, W. Eric, and L. Grimson, "Fixed Topology Skeletons," Proc. IEEE Conf. Computer Vision and Pattern Recognition, vol. 1, pp. 10-17, 2000.
[19] G. Yaorong and J.M. Fitzpatrick, "On the Generation of Skeletons from Discrete Euclidean Distance Maps," IEEE Trans. Pattern Analysis and Machine Intelligence, vol. 18, no. 11, pp. 1055-1066, Nov. 1996.
[20] G. Borgefors, "Distance Transformations in Digital Images," Computer Vision, Graphics, and Image Processing, vol. 34, no. 3, pp. 344-371, June 1986.
[21] P. Dimitrov, J.N. Damon, and K. Siddiqi, "Flux Invariants for Shape," Proc. IEEE CS Conf. Computer Vision and Pattern Recognition, pp. I-835-I-841, 2003.
[22] K. Siddiqi, S. Bouix, A. Tannenbaum, and S.W. Zucker, "Hamilton-Jacobi Skeletons," Int'l J. Computer Vision, vol. 48, no. 3, pp. 215-231, 2002.
[23] K. Palágyi, E. Balogh, A. Kuba, C. Halmai, B. Erdőhelyi, E. Sorantin, and K. Hausegger, "A Sequential 3D Thinning Algorithm and Its Medical Applications," Proc. 17th Int'l Conf. Information Processing in Medical Imaging, pp. 409-415, 2001.
[24] S. Svensson, I. Nystrom, C. Arcelli, and G. Sanniti di Baja, "Using Grey-Level and Distance Information for Medial Surface Representation of Volume Images," Proc. 16th Int'l Conf. Pattern Recognition, vol. 2, pp. 324-327, 2002.
[25] S.S. Abeysinghe, M. Baker, C. Wah, and J. Tao, "Segmentation-Free Skeletonization of Grayscale Volumes for Shape Understanding," Proc. IEEE Int'l Conf. Shape Modeling and Applications, pp. 63-71, 2008.
[26] E. Antunez and L. Guibas, "Robust Extraction of 1D Skeletons from Grayscale 3D Images," Proc. 19th Int'l Conf. Pattern Recognition, pp. 1-4, 2008.
[27] M. Couprie, F. Bezerra, and G. Bertrand, "Topological Operators for Grayscale Image Processing," J. Electronic Imaging, vol. 10, no. 4, pp. 1003-1015, 2001.
[28] P. Dokládal, C. Lohou, L. Perroton, and G. Bertrand, "A New Thinning Algorithm and Its Application to Extraction of Blood Vessels," Proc. First Conf. on Modelling and Simulation in Biology, Medicine and Biomedical Engineering (BioMedSim '99), pp. 32-37, 2009.
[29] Z. Song, C. Demiralp, and D.H. Laidlaw, "Visualizing Diffusion Tensor MR Images Using Streamtubes and Streamsurfaces," IEEE Trans. Visualization and Computer Graphics, vol. 9, no. 4, pp. 454-462, Oct.-Dec. 2003.
[30] Y. Zeyun and C. Bajaj, "A Structure Tensor Approach for 3D Image Skeletonization: Applications in Protein Secondary Structure Analysis," Proc. IEEE Int'l Conf. Image Processing, pp. 2513-2516, 2006.
[31] K. Al Nasr, L. Chen, D. Si, D. Ranjan, M. Zubair, and J. He, "Building the Initial Chain of the Proteins through De Novo Modeling of the Cryo-Electron Microscopy Volume Data at the Medium Resolutions," Proc. ACM Conf. Bioinformatics Computational Biology and Biomedicine, pp. 490-497, 2012.
[32] K. Al Nasr, D. Ranjan, M. Zubair, and J. He, "Ranking Valid Topologies of the Secondary Structure Elements Using a Constraint Graph," J. Bioinformatics and Computational Biology, vol. 9, no. 3, pp. 415-430, 2011.
[33] K. Al Nasr, W. Sun, and J. He, "Structure Prediction for the Helical Skeletons Detected from the Low Resolution Protein Density Map," BMC Bioinformatics, vol. 11, no. Suppl. 1, article S44, Jan. 2010.
[34] M.L. Baker, S.S. Abeysinghe, S. Schuh, R.A. Coleman, A. Abrams, M.P. Marsh, C.F. Hryc, T. Ruths, W. Chiu, and T. Ju, "Modeling Protein Structure at Near Atomic Resolutions with Gorgon," J. Structural Biology, vol. 174, no. 2, pp. 360-373, 2011.
[35] W. Chiu and M.F. Schmid, "Pushing Back the Limits of Electron Cryomicroscopy," Nature Structural Biology, vol. 4, pp. 331-333, 1997.
[36] Z.H. Zhou, M. Dougherty, J. Jakana, J. He, F.J. Rixon, and W. Chiu, "Seeing the Herpesvirus Capsid at 8.5 A," Science, vol. 288, no. 5467, pp. 877-80, May 2000.
[37] D.H Chen, S.J Ludtke, J.L Song, D.T Chuang, and W. Chiu, "Seeing GroEL at 6 A Resolution by Single Particle Electron Cryomicroscopy," Structure, vol. 12, no. 7, pp. 1129-36, July 2004.
[38] W. Chiu, M.L. Baker, W. Jiang, and Z.H. Zhou, "Deriving Folds of Macromolecular Complexes through Electron Cryomicroscopy and Bioinformatics Approaches," Current Opinion in Structural Biology, vol. 12, no. 2, pp. 263-269, Apr. 2002.
[39] X. Zhang, L. Jin, Q. Fang, W.H. Hui, and Z.H. Zhou, "3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry," Cell, vol. 141, no. 3, pp. 472-482, Apr. 2010.
[40] L. Cheng, J. Sun, K. Zhang, Z. Mou, X. Huang, G. Ji, F. Sun, J. Zhang, and P. Zhu, "Atomic Model of a Cypovirus Built from Cryo-EM Structure Provides Insight into the Mechanism of mRNA Capping," Proc. Nat'l Academy of Sciences USA, vol. 108, no. 4, pp. 1373-1378, Jan. 2011.
[41] S. Maki-Yonekura, K. Yonekura, and K. Namba, "Conformational Change of Flagellin for Polymorphic Supercoiling of the Flagellar Filament," Nature Structural & Molecular Biology, vol. 17, no. 4, pp. 417-422, Apr. 2010.
[42] X. Yu, P. Ge, J. Jiang, I. Atanasov, and Z.H. Zhou, "Atomic Model of CPV Reveals the Mechanism Used by This Single-Shelled Virus to Economically Carry Out Functions Conserved in Multishelled Reoviruses," Structure, vol. 19, no. 5, pp. 652-661, 2011.
[43] B. Böttcher, S.A. Wynne, and R.A. Crowther, "Determination of the Fold of the Core Protein of Hepatitis B Virus by Electron Cryomicroscopy," Nature, vol. 386, no. 6620, pp. 88-91, 1997.
[44] J.F. Conway, N. Cheng, A. Zlotnick, P.T. Wingfield, S.J. Stahl, and A.C. Steven, "Visualization of a 4-Helix Bundle in the Hepatitis B Virus Capsid by Cryo-Electron Microscopy," Nature, vol. 386, no. 6620, pp. 91-94, 1997.
[45] M.L. Baker, W. Jiang, W.J. Wedemeyer, F.J. Rixon, D. Baker, and W. Chiu, "Ab Initio Modeling of the Herpesvirus VP26 Core Domain Assessed by CryoEM Density," PLoS Computational Biology, vol. 2, no. 10,article e146, Oct. 2006.
[46] A.G. Martin, F. Depoix, M. Stohr, U. Meissner, S. Hagner-Holler, K. Hammouti, T. Burmester, J. Heyd, W. Wriggers, and J. Markl, "Limulus Polyphemus Hemocyanin: 10 A Cryo-EM Structure, Sequence Analysis, Molecular Modelling and Rigid-Body Fitting Reveal the Interfaces between the Eight Hexamers," J. Molecular Biology, vol. 366, no. 4, pp. 1332-1350, Mar. 2007.
[47] E. Villa, J. Sengupta, L.G. Trabuco, J. LeBarron, W.T. Baxter, T.R. Shaikh, R.A. Grassucci, P. Nissen, M. Ehrenberg, K. Schulten, and J. Frank, "Ribosome-Induced Changes in Elongation Factor Tu Conformation Control GTP Hydrolysis," Proc. Nat'l Academy of Sciences USA, vol. 106, no. 4, pp. 1063-1068, Jan. 2009.
[48] C.L. Lawson, M.L. Baker, C. Best, C. Bi, M. Dougherty, P. Feng, G. van Ginkel, B. Devkota, I. Lagerstedt, S.J. Ludtke, R.H. Newman, T.J. Oldfield, I. Rees, G. Sahni, R. Sala, S. Velankar, J. Warren, J.D. Westbrook, K. Henrick, G.J. Kleywegt, H.M. Berman, and W. Chiu, "EMDataBank.org: Unified Data Resource for CryoEM," Nucleic Acids Research, vol. 39, no. suppl. 1, pp. D456-D464, Jan. 2011.
[49] D. Si, S. Ji, K. Al Nasr, and J. He, "A Machine Learning Approach for the Identification of Protein Secondary Structure Elements from Cryoem Density Maps," Biopolymers, vol. 97, pp. 698-708, 2012.
[50] K. Lasker, O. Dror, M. Shatsky, R. Nussinov, and H.J. Wolfson, "EMatch: Discovery of High Resolution Structural Homologues of Protein Domains in Intermediate Resolution Cryo-EM Maps," IEEE/ACM Trans. Computational Biology and Bioinformatics, vol. 4, no. 1, pp. 28-39, Jan. 2007.
[51] A. Del Palu, J. He, E. Pontelli, and Y. Lu, "Identification of Alpha-Helices from Low Resolution Protein Density Maps," Proc. Computational Systems Bioinformatics Conf. (CSB '06), pp. 89-98, 2006.
[52] G. Pollastri and A. McLysaght, "Porter: A New, Accurate Server for Protein Secondary Structure Prediction," Bioinformatics, vol. 21, no. 8, pp. 1719-20, Apr. 2005.
[53] D.T. Jones, "Protein Secondary Structure Prediction Based on Position-Specific Scoring Matrices," J. Molecular Biology, vol. 292, no. 2, pp. 195-202, Sept. 1999.
[54] K. Al Nasr, "De Novo Protein Structure Modeling from Cryoem Data through a Dynamic Programming Algorithm in the Secondary Structure Topology Graph," Dissertation, Dept. of Computer Science, Old Dominion Univ., 2012.
[55] S. Lindert, N. Alexander, N. Wötzel, M. Karaka, P.L. Stewart, and J. Meiler, "EM-Fold: De Novo Atomic-Detail Protein Structure Determination from Medium-Resolution Density Maps," Structure, vol. 20, no. 3, pp. 464-478, 2012.
[56] S. Lindert, R. Staritzbichler, N. Wötzel, M. Karakaş, P.L. Stewart, and J. Meiler, "EM-Fold: De Novo Folding of α-Helical Proteins Guided by Intermediate-Resolution Electron Microscopy Density Maps," Structure, vol. 17, no. 7, pp. 990-1003, July 2009.
[57] J. He, Y. Lu, and E. Pontelli, "A Parallel Algorithm for Helix Mapping between 3D and 1D Protein Structure Using the Length Constraints," Proc. Second Int'l Conf. Parallel and Distributed Processing and Applications, pp. 746-756, 2004.
[58] A. Dal Palu, E. Pontelli, J. He, and Y. Lu, "A Constraint Logic Programming Approach to 3D Structure Determination of Large Protein Complexes," Proc. ACM Symp. Applied Computing, pp. 131-136, 2006.
[59] Y. Wu, M. Chen, M. Lu, Q. Wang, and J. Ma, "Determining Protein Topology from Skeletons of Secondary Structures," J. Molecular Biology, vol. 350, no. 3, pp. 571-86, July 2005.
[60] S.S. Abeysinghe and T. Ju, "Interactive Skeletonization of Intensity Volumes," Visual Computer, vol. 25, nos. 5-7, pp. 627-635, 2009.
[61] Y. Kong, X. Zhang, T.S. Baker, and J. Ma, "A Structural-Informatics Approach for Tracing Beta-Sheets: Building Pseudo-C(Alpha) Traces for Beta-Strands in Intermediate-Resolution Density Maps," J. Molecular Biology, vol. 339, no. 1, pp. 117-30, May 2004.
[62] E.W. Dijkstra, "A Note on Two Problems in Connexion with Graphs," Numerische Mathematik, vol. 1, no. 1, pp. 269-271, 1959.
[63] Y. Cong, Q. Zhang, D. Woolford, T. Schweikardt, H. Khant, M. Dougherty, S.J. Ludtke, W. Chiu, and H. Decker, "Structural Mechanism of SDS-Induced Enzyme Activity of Scorpion Hemocyanin Revealed by Electron Cryomicroscopy," Structure, vol. 17, no. 5, pp. 749-758, 2009.
[64] T. Fujii, M. Cheung, A. Blanco, T. Kato, A.J. Blocker, and K. Namba, "Structure of a Type III Secretion Needle at 7-Å Resolution Provides Insights into Its Assembly and Signaling Mechanisms," Proc. Nat'l Academy of Sciences USA, vol. 109, no. 12, pp. 4461-4466, Mar. 2012.
[65] S. Bhushan, T. Hoffmann, B. Seidelt, J. Frauenfeld, T. Mielke, O. Berninghausen, D.N. Wilson, and R. Beckmann, "SecM-Stalled Ribosomes Adopt an Altered Geometry at the Peptidyl Transferase Center," PLoS Biology, vol. 9, no. 1,article e1000581, 2011.
331 ms
(Ver 2.0)

Marketing Automation Platform Marketing Automation Tool