914 research outputs found
Orthogonal Matrix Retrieval in Cryo-Electron Microscopy
In single particle reconstruction (SPR) from cryo-electron microscopy
(cryo-EM), the 3D structure of a molecule needs to be determined from its 2D
projection images taken at unknown viewing directions. Zvi Kam showed already
in 1980 that the autocorrelation function of the 3D molecule over the rotation
group SO(3) can be estimated from 2D projection images whose viewing directions
are uniformly distributed over the sphere. The autocorrelation function
determines the expansion coefficients of the 3D molecule in spherical harmonics
up to an orthogonal matrix of size for each
. In this paper we show how techniques for solving the phase
retrieval problem in X-ray crystallography can be modified for the cryo-EM
setup for retrieving the missing orthogonal matrices. Specifically, we present
two new approaches that we term Orthogonal Extension and Orthogonal
Replacement, in which the main algorithmic components are the singular value
decomposition and semidefinite programming. We demonstrate the utility of these
approaches through numerical experiments on simulated data.Comment: Modified introduction and summary. Accepted to the IEEE International
Symposium on Biomedical Imagin
3D ab initio modeling in cryo-EM by autocorrelation analysis
Single-Particle Reconstruction (SPR) in Cryo-Electron Microscopy (cryo-EM) is
the task of estimating the 3D structure of a molecule from a set of noisy 2D
projections, taken from unknown viewing directions. Many algorithms for SPR
start from an initial reference molecule, and alternate between refining the
estimated viewing angles given the molecule, and refining the molecule given
the viewing angles. This scheme is called iterative refinement. Reliance on an
initial, user-chosen reference introduces model bias, and poor initialization
can lead to slow convergence. Furthermore, since no ground truth is available
for an unsolved molecule, it is difficult to validate the obtained results.
This creates the need for high quality ab initio models that can be quickly
obtained from experimental data with minimal priors, and which can also be used
for validation. We propose a procedure to obtain such an ab initio model
directly from raw data using Kam's autocorrelation method. Kam's method has
been known since 1980, but it leads to an underdetermined system, with missing
orthogonal matrices. Until now, this system has been solved only for special
cases, such as highly symmetric molecules or molecules for which a homologous
structure was already available. In this paper, we show that knowledge of just
two clean projections is sufficient to guarantee a unique solution to the
system. This system is solved by an optimization-based heuristic. For the first
time, we are then able to obtain a low-resolution ab initio model of an
asymmetric molecule directly from raw data, without 2D class averaging and
without tilting. Numerical results are presented on both synthetic and
experimental data
Disentangling Orthogonal Matrices
Motivated by a certain molecular reconstruction methodology in cryo-electron
microscopy, we consider the problem of solving a linear system with two unknown
orthogonal matrices, which is a generalization of the well-known orthogonal
Procrustes problem. We propose an algorithm based on a semi-definite
programming (SDP) relaxation, and give a theoretical guarantee for its
performance. Both theoretically and empirically, the proposed algorithm
performs better than the na\"{i}ve approach of solving the linear system
directly without the orthogonal constraints. We also consider the
generalization to linear systems with more than two unknown orthogonal
matrices
Bispectrum Inversion with Application to Multireference Alignment
We consider the problem of estimating a signal from noisy
circularly-translated versions of itself, called multireference alignment
(MRA). One natural approach to MRA could be to estimate the shifts of the
observations first, and infer the signal by aligning and averaging the data. In
contrast, we consider a method based on estimating the signal directly, using
features of the signal that are invariant under translations. Specifically, we
estimate the power spectrum and the bispectrum of the signal from the
observations. Under mild assumptions, these invariant features contain enough
information to infer the signal. In particular, the bispectrum can be used to
estimate the Fourier phases. To this end, we propose and analyze a few
algorithms. Our main methods consist of non-convex optimization over the smooth
manifold of phases. Empirically, in the absence of noise, these non-convex
algorithms appear to converge to the target signal with random initialization.
The algorithms are also robust to noise. We then suggest three additional
methods. These methods are based on frequency marching, semidefinite relaxation
and integer programming. The first two methods provably recover the phases
exactly in the absence of noise. In the high noise level regime, the invariant
features approach for MRA results in stable estimation if the number of
measurements scales like the cube of the noise variance, which is the
information-theoretic rate. Additionally, it requires only one pass over the
data which is important at low signal-to-noise ratio when the number of
observations must be large
Autocorrelation analysis for cryo-EM with sparsity constraints: Improved sample complexity and projection-based algorithms
The number of noisy images required for molecular reconstruction in
single-particle cryo-electron microscopy (cryo-EM) is governed by the
autocorrelations of the observed, randomly-oriented, noisy projection images.
In this work, we consider the effect of imposing sparsity priors on the
molecule. We use techniques from signal processing, optimization, and applied
algebraic geometry to obtain new theoretical and computational contributions
for this challenging non-linear inverse problem with sparsity constraints. We
prove that molecular structures modeled as sums of Gaussians are uniquely
determined by the second-order autocorrelation of their projection images,
implying that the sample complexity is proportional to the square of the
variance of the noise. This theory improves upon the non-sparse case, where the
third-order autocorrelation is required for uniformly-oriented particle images
and the sample complexity scales with the cube of the noise variance.
Furthermore, we build a computational framework to reconstruct molecular
structures which are sparse in the wavelet basis. This method combines the
sparse representation for the molecule with projection-based techniques used
for phase retrieval in X-ray crystallography.Comment: 31 pages, 5 figures, 1 movi
Toward single particle reconstruction without particle picking: Breaking the detection limit
Single-particle cryo-electron microscopy (cryo-EM) has recently joined X-ray
crystallography and NMR spectroscopy as a high-resolution structural method for
biological macromolecules. In a cryo-EM experiment, the microscope produces
images called micrographs. Projections of the molecule of interest are embedded
in the micrographs at unknown locations, and under unknown viewing directions.
Standard imaging techniques first locate these projections (detection) and then
reconstruct the 3-D structure from them. Unfortunately, high noise levels
hinder detection. When reliable detection is rendered impossible, the standard
techniques fail. This is a problem especially for small molecules, which can be
particularly hard to detect. In this paper, we propose a radically different
approach: we contend that the structure could, in principle, be reconstructed
directly from the micrographs, without intermediate detection. As a result,
even small molecules should be within reach for cryo-EM. To support this claim,
we setup a simplified mathematical model and demonstrate how our
autocorrelation analysis technique allows to go directly from the micrographs
to the sought signals. This involves only one pass over the micrographs, which
is desirable for large experiments. We show numerical results and discuss
challenges that lay ahead to turn this proof-of-concept into a competitive
alternative to state-of-the-art algorithms
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