title: Maximum-likelihood multi-reference refinement for electron microscopy images.
abstract: A maximum-likelihood approach to multi-reference image refinement is presented. In contrast to conventional cross-correlation refinement, the new approach includes a formal description of the noise, implying that it is especially suited to cases with low signal-to-noise ratios. Application of this approach to a cryo-electron microscopy dataset revealed two major classes for projections of simian virus 40 large T-antigen in complex with an asymmetric DNA-probe, containing the origin of simian virus 40 replication. Strongly bent projections of dodecamers showed density that may be attributed to the complexed double-stranded DNA, while almost straight projections revealed a twist in the relative orientation of the hexameric subunits. This new level of detail for large T-antigen projections was not detected using conventional techniques. For a negative stain dataset, maximum-likelihood refinement yielded results that were practically identical to those obtained using conventional multi-reference refinement. Results obtained using simulated data suggest that the efficiency of the maximum-likelihood approach may be further enhanced by explicitly incorporating the microscope contrast transfer function in the image formation model.
authors.affiliation: Biocomputing Unit, Centro Nacional de Biotecnología, Campus Universidad Autónoma, Cantoblanco, 28049, Madrid, Spain.
authors.forename: Sjors H W
authors.initials: SH
authors.lastname: Scheres
authors.forename: Mikel
authors.initials: M
authors.lastname: Valle
authors.forename: Rafael
authors.initials: R
authors.lastname: Nuñez
authors.forename: Carlos O S
authors.initials: CO
authors.lastname: Sorzano
authors.forename: Roberto
authors.initials: R
authors.lastname: Marabini
authors.forename: Gabor T
authors.initials: GT
authors.lastname: Herman
authors.forename: Jose-Maria
authors.initials: JM
authors.lastname: Carazo
mesh_terms: D000465:Algorithms; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D020285:Cryoelectron Microscopy / Q000379:methods*; D016013:Likelihood Functions; D008433:Mathematics; D018741:Replication Origin; D013539:Simian virus 40
chemical_list: D000952:Antigens, Polyomavirus Transforming