AB Initio Tomography With Object Heterogeneity and Unknown Viewing Paramete

In this paper, we present an algorithm to automatically construct all the conformations of a heterogeneous planar object from their tomographic projections at random unknown view angles. Our statistically motivated approach can reveal and analyze the heterogeneity in the projection dataset and segregate the projections belonging to different structures without requiring prior structural information or templates, expert human intervention or even the knowledge of the number of conformations present in the sample. Even in the presence of high noise variance (low SNR) and a large number of conformations, our algorithm can estimate the structures of each conformation to a high degree of accuracy. We demonstrate the broad applicability of our algorithm by evaluating its performance on synthetic 2D datasets of well-known protein complexes such as Lipase under varying levels of noise and different number of conformations.

[1]  Sjors H. W. Scheres A Bayesian view on cryo-EM structure determination , 2012, ISBI.

[2]  S. C. Johnson Hierarchical clustering schemes , 1967, Psychometrika.

[3]  M. Baumann,et al.  Techniques for studying protein heterogeneity and post-translational modifications , 2004, Expert review of proteomics.

[4]  F. Natterer The Mathematics of Computerized Tomography , 1986 .

[5]  Thomas W. Parks,et al.  Adaptive principal components and image denoising , 2003, Proceedings 2003 International Conference on Image Processing (Cat. No.03CH37429).

[6]  Nikolaus Grigorieff,et al.  FREALIGN: high-resolution refinement of single particle structures. , 2007, Journal of structural biology.

[7]  H. Saibil,et al.  Allosteric signaling of ATP hydrolysis in GroEL–GroES complexes , 2006, Nature Structural &Molecular Biology.

[8]  Étienne Baudrier,et al.  Retrieving the parameters of cryo Electron Microscopy dataset in the heterogeneous ab-initio case , 2016, 2016 IEEE International Conference on Image Processing (ICIP).

[9]  J Bernard Heymann,et al.  Molecular dynamics of protein complexes from four-dimensional cryo-electron microscopy. , 2004, Journal of structural biology.

[10]  C. O. S. Sorzano,et al.  Particle alignment reliability in single particle electron cryomicroscopy: a general approach , 2016, Scientific Reports.

[11]  E. Orlova,et al.  Detection and separation of heterogeneity in molecular complexes by statistical analysis of their two-dimensional projections. , 2008, Journal of structural biology.

[12]  Joachim Frank,et al.  Dynamics of EF-G interaction with the ribosome explored by classification of a heterogeneous cryo-EM dataset. , 2004, Journal of structural biology.

[13]  Ajit Rajwade,et al.  Tomographic reconstruction from projections with unknown view angles exploiting moment-based relationships , 2016, 2016 IEEE International Conference on Image Processing (ICIP).

[14]  John E. Johnson,et al.  Time-resolved molecular dynamics of bacteriophage HK97 capsid maturation interpreted by electron cryo-microscopy and X-ray crystallography. , 2006, Journal of structural biology.

[15]  Étienne Baudrier,et al.  A tomographical reconstruction method from unknown direction projections for 2D gray-level images , 2014, 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI).

[16]  Y Bresler,et al.  Feasibility of tomography with unknown view angles , 2000, IEEE Trans. Image Process..

[17]  Amit Singer,et al.  Two-Dimensional Tomography from Noisy Projections Taken at Unknown Random Directions , 2013, SIAM J. Imaging Sci..

[18]  J. Frank EXPLORING THE DYNAMICS OF SUPRAMOLECULAR MACHINES WITH CRYO-ELECTRON MICROSCOPY , 2014 .

[19]  Ajit Rajwade,et al.  Noise- and Outlier-Resistant Tomographic Reconstruction under Unknown Viewing Parameters , 2018 .

[20]  Ronald R. Coifman,et al.  Graph Laplacian Tomography From Unknown Random Projections , 2008, IEEE Transactions on Image Processing.

[21]  David J. Fleet,et al.  cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination , 2017, Nature Methods.

[22]  Steven Chu,et al.  tRNA dynamics on the ribosome during translation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J M Carazo,et al.  A clustering approach to multireference alignment of single-particle projections in electron microscopy. , 2010, Journal of structural biology.

[24]  Fionn Murtagh,et al.  A Survey of Recent Advances in Hierarchical Clustering Algorithms , 1983, Comput. J..

[25]  J. Frank Three-Dimensional Electron Microscopy of Macromolecular Assemblies , 2006 .

[26]  Thomas Walz,et al.  Single particle reconstructions of the transferrin-transferrin receptor complex obtained with different specimen preparation techniques. , 2006, Journal of molecular biology.

[27]  M. Gerstein,et al.  A database of macromolecular motions. , 1998, Nucleic acids research.