title: Noise models and cryo-EM drift correction with a direct-electron camera.
abstract: Blurring due to specimen-holder drift is a common occurrence in cryo-EM images. Cameras employing active-pixel sensors are capable of high frame rates such that a single low-dose exposure can be acquired as a series of frames. In this paper we consider the possibility of tracking and compensating for overall drift in typical single-particle specimens through the analysis of frame sequences. A problem that arises in tracking through cross-correlation of frames obtained with the DE-12 camera from Direct Electron LLC is the presence of "hot-pixel noise". This random pattern of bright pixels is highly correlated among frames. We show how a model of this noise can be employed to greatly reduce its effects. A filter function is derived that optimizes the tracking of image shifts by cross-correlation, and we demonstrate the tracking of specimen drift in typical cryo-EM specimens.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University, 333 Cedar Street, New Haven, CT 06520, United States. hideki.shigematsu@yale.edu
authors.forename: H
authors.initials: H
authors.lastname: Shigematsu
authors.forename: F J
authors.initials: FJ
authors.lastname: Sigworth
keywords: CMOS; Complementary metal-oxide-semiconductor; Cross-correlation function; Cryo-EM; Electron cryomicroscopy; Transmission electron microscopy