title: Maximum likelihood based classification of electron tomographic data.
abstract: Classification and averaging of sub-tomograms can improve the fidelity and resolution of structures obtained by electron tomography. Here we present a three-dimensional (3D) maximum likelihood algorithm--MLTOMO--which is characterized by integrating 3D alignment and classification into a single, unified processing step. The novelty of our approach lies in the way we calculate the probability of observing an individual sub-tomogram for a given reference structure. We assume that the reference structure is affected by a 'compound wedge', resulting from the summation of many individual missing wedges in distinct orientations. The distance metric underlying our probability calculations effectively down-weights Fourier components that are observed less frequently. Simulations demonstrate that MLTOMO clearly outperforms the 'constrained correlation' approach and has advantages over existing approaches in cases where the sub-tomograms adopt preferred orientations. Application of our approach to cryo-electron tomographic data of ice-embedded thermosomes revealed distinct conformations that are in good agreement with results obtained by previous single particle studies.
authors: Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
authors: Michael
authors: M
authors: Stölken
authors: Florian
authors: F
authors: Beck
authors: Thomas
authors: T
authors: Haller
authors: Reiner
authors: R
authors: Hegerl
authors: Irina
authors: I
authors: Gutsche
authors: Jose-Maria
authors: JM
authors: Carazo
authors: Wolfgang
authors: W
authors: Baumeister
authors: Sjors H W
authors: SH
authors: Scheres
authors: Stephan
authors: S
authors: Nickell
mesh_terms: D000465:Algorithms; D003627:Data Interpretation, Statistical; D055032:Electron Microscope Tomography / Q000145:classification / Q000379:methods* / Q000706:statistics & numerical data*; D016013:Likelihood Functions; D008958:Models, Molecular; D056405:Thermosomes / Q000737:chemistry*
chemical_list: D056405:Thermosomes