-
Dr Leslie Greengard (CCM Director)8/8/19, 9:00 AM
-
Dr Joachim Frank8/8/19, 9:10 AM
The ability of single-particle cryo-EM to furnish hundreds of thousand images of molecules fast-frozen in solution means that even rarely sighted conformations, corresponding to high-energy states, are represented in the data set. As a consequence, a continuum of states is experimentally accessible (Frank, Biochemistry 2018). Current practice of cryo-EM structure research does not take...
Go to contribution page -
Dr Bridget Carragher8/8/19, 9:50 AM
-
Dr Ayelet Heimowitz8/8/19, 11:00 AM
"Particle picking is a crucial first step in the computational pipeline of single-particle cryo-electron microscopy. Selecting particles from the micrographs is difficult especially for small particles with low contrast. As high-resolution reconstruction typically requires hundreds of thousands of particles, including rare views, manual picking is often too time-consuming. While template-based...
Go to contribution page -
Dr Joe Kileel8/8/19, 11:40 AM
In 1980, Zvi Kam introduced an autocorrelation-based approach to cryo-electron microscopy (cryo-EM) single particle reconstruction, in which moments of the 2D images are computed and the 3D molecule is recovered by solving a polynomial system of equations. Recently, the method has also been used in X-ray free electron laser (XFEL) imaging.
This talk addresses important challenges in applying...
Go to contribution page -
Dr Pilar Cossio8/8/19, 2:00 PM
Cryo-electron microscopy is a revolutionary technique that can Provide 3D density maps at near atomic resolution. However, map validation is still an open issue in the field. Despite several efforts from the community, it is possible to overfit the reconstructions to noisy data. Here, inspired by modern statistics, we develop a novel methodology that uses a small independent particle set to...
Go to contribution page -
Dr Jose Maria Carazo8/8/19, 2:40 PM
I will introduce the notion of Directional Local Resolution, extending the current practice in CryoEM around local resolution. In this way, local resolution becomes a tensor. I will then present the wide range of new opportunities that this extension opens, while focusing during the presentation mostly in map validation and sharpening
Go to contribution page -
Dr Alberto Bartesaghi8/8/19, 3:50 PM
Automated protocols for data acquisition used in modern cryo-EM facilities combined with the newer generation of larger and faster cameras have dramatically increased the throughput of data collection, exacerbating the need to develop effective strategies for structure determination that can operate without a user in the loop in order to keep up with the rate of data production. I’ll present...
Go to contribution page -
Dr Richard Henderson8/8/19, 4:30 PM
Single particle cryo-EM images are still not perfect. I will discuss some work that Chris Russo and I have done recently to identify the remaining sources of imperfection and what might be done either by computation or by experimentation to overcome these problems.
Go to contribution page -
Dr Amaya Jimenez-Moreno (National Center of Biotechnology (CSIC))8/8/19, 5:15 PM
Cryo Electron Microscopy (Cryo-EM) is currently one of the main tools to reveal the structural information of biological specimens. However, in a common Cryo-EM processing workflow, the 3D alignment step, due to the very low signal-to-noise ratio of Cryo-EM images, is a prone error process. Thus, the reconstructed 3D maps can show areas with low resolution.
In this work, a novel method to...
Go to contribution page -
Yunye Gong (Cornell University), Prof. Peter C. Doerschuk (Cornell University)8/8/19, 5:15 PM
The goal of this research is to understand the dynamical motion of nanoscale biological machines such as viruses directly from large sets of data. The ideal data would be 4-D measurements (3 spatial and 1 temporal) on each instance of the machine. The most informative available data are 2-D cryo-electron microscopy projection images of flash-frozen instances, one image for each instance....
Go to contribution page -
Mrs Yifeng Fan8/8/19, 5:15 PM
Cryo-electron microscopy (EM) single particle reconstruction is an entirely general technique for 3D structure determination of macromolecular complexes. However, because the images are taken at low electron dose, it is extremely hard to visualize the individual particle with low contrast and high noise level. In this paper, we propose a novel approach called multi-frequency vector diffusion...
Go to contribution page -
33. Deep learning and image analysis tools for automated analysis and assessment of cryo-EM datasetsYilai Li (University of Michigan)8/8/19, 5:15 PM
The growth of cryo-EM into a mainstream structural biology tool has led to its widespread adoption for users across a range of expertise, where experts represents a small fraction of cryo-EM users. Considering the manual and subjective decisions involved in solving a structure, such as the programs, parameters and determination of good micrographs and good 2D class averages, cryo-EM frustrates...
Go to contribution page -
Dr David Maluenda (National Center of Biotechnology (CSIC))8/8/19, 5:15 PM
Cryo-EM workflows require from tens of thousands of high-quality particle projections to unveil the three-dimensional structure of macromolecules. Current methods for automatic particle-picking tend to suffer from high false-positive rates, hurdling the reconstruction process. Usually, the failures of one particle-picking algorithm are typically not the failures of another. Therefore, a smart...
Go to contribution page -
Dr Erney Ramírez-Aportela (CNB-CSIC (Madrid, Spain))8/8/19, 5:15 PM
We present a method to estimate a new local quality measure for 3D cryoEM maps that adopts the form of a local resolution-type of information. The algorithm (DeepRes) is based on deep learning 3D features detection. DeepRes is fully automatic and parameter free and avoids issues of most current methods, such as their insensitivity to enhancements due to B-factor sharpening (unless the 3D mask...
Go to contribution page -
Prof. Aaditya Rangan (New York University)8/8/19, 5:15 PM
An important subproblem in image analysis is the comparison of different images, which usually involves the calculation of inner products between pairs of images. In this poster we provide a new method for computing such inner products for arbitrary rotations and a user-specified range of translations. Our method takes advantage of the Fourier–Bessel basis to efficiently handle rotations,...
Go to contribution page -
Dr Sonya M. Hanson (Max Planck Institute of Biophysics)8/8/19, 5:15 PM
The TRPV1 ion channel is a heat sensor that plays a key role in pain sensing pathways. Recent advances in cryo-electron microscopy (cryo-EM) have facilitated a recent explosion in the availability of TRP channel structures. Despite these structures, the temperature-sensing mechanism of any TRP channel remains poorly understood. The manifold embedding method in cryo-EM allows the identification...
Go to contribution page -
Prof. Peter Schwander (University of Wisconsin Milwaukeee)8/8/19, 5:15 PM
We have developed a manifold-based machine-learning approach for analyzing cryoEM single-particle data. This approach is capable of mapping continuous conformational changes of biological molecules along any user-selected trajectory on the energy landscape, without timing information, supervision, or templates. Our unbiased approach (1) reveals the number of degrees of freedom exercised...
Go to contribution page -
Ayelet Heimowitz (Princeton University)8/8/19, 5:15 PM
We present a novel method for contrast transfer function (CTF) estimation. Our method is based on the multi-taper method for power spectral density estimation, which aims to reduce the bias and variance of the estimator. Furthermore, we use known properties of the CTF and of the background of the power spectrum to increase the accuracy of our estimation. We will show that the resulting...
Go to contribution page -
William Leeb (University of Minnesota)8/8/19, 5:15 PM
We will present recent work on the problem of simultaneously denoising cryo-EM images and correcting for the effects of the contrast transfer function (CTF). The methods used are based on new results from high-dimensional principal component analysis and matrix recovery in the spiked covariance model. We use new spectral shrinkers that account for the effects of both the CTF and the colored...
Go to contribution page -
Dr Philip Baldwin (The Salk Institute)8/8/19, 5:15 PM
Virtually every single-particle cryo-EM experiment currently suffers from specimen adherence to the air-water interface, leading to a non-uniform distribution in the set of projection views. Non-uniform (anisotropic) distributions can negatively affect map quality, elongate structural features, and in some cases, prohibit interpretation altogether. Although some consequences of non-uniform...
Go to contribution page -
Tristan Bepler8/8/19, 5:15 PM
Cryo-electron microscopy is a popular method for protein structure determination. Identifying a sufficient number of particles for analysis can take months of manual effort. Current computational approaches find many false positives and require significant ad hoc post-processing, especially for unusually-shaped particles. To address these shortcomings, we develop Topaz, an efficient and...
Go to contribution page -
Dr Étienne Baudrier8/8/19, 5:15 PM
The scope of this paper is the tomographic reconstruction of the observed object in the ab-initio case where the volume has to be estimated only from a raw projection dataset. A new fast approach based on a parametric model of the volume is presented. The description of the model and the search of the parameters are detailed. The accuracy and robustness of the proposed reconstruction method is...
Go to contribution page -
Ellen Zhong (Massachusetts Institute of Technology)8/8/19, 5:15 PM
In single particle cryo-EM, the central problem is to reconstruct the three-dimensional structure of a protein from $10^4-10^7$ noisy and randomly oriented two-dimensional projections. However, the imaged protein molecules may exhibit structural variability, which complicates reconstruction and is typically addressed using discrete clustering approaches that fail to capture the full range of...
Go to contribution page -
Amit Halevi (Princeton University), Dr Amit Moscovich (Princeton University)8/8/19, 5:15 PM
In this work, we address the continuous heterogeneity problem. We parametrize the 3D density maps of the particles being imaged using a low-dimensional manifold of conformations. This parametrization is based on low-resolution reconstructions and Laplacian eigenmaps. We use this parametrization to form a generalized tomographic reconstruction problem which reconstructs a density map at each...
Go to contribution page -
James Chen8/8/19, 5:15 PM
Single-particle EM 3D reconstruction comprises two aspects: data acquisition and data analysis. While “data analysis” aims to extract as much information as possible from noisy raw images, “data acquisition” strives to maximize the amount of information in data recording.
Electron scattering cross-sections of heavy atoms quantitatively differ from light atoms (namely C, N, O) abundant in...
Go to contribution page -
Dr Marin Van Heel8/9/19, 9:00 AM
In recent years we have seen an avalanche of cryo-EM (cryogenic Electron Microscopy) publications presenting beautiful biological structures at resolution levels of even better than ~3Å! This true “resolution revolution” has culminated in the 2017 Nobel prize for Chemistry being awarded for single-particle cryo-EM. Impressive as these results may be (and continue to be), various fundamental -...
Go to contribution page -
Dr Gregory Chirikjian8/9/19, 9:40 AM
This talk discusses information fusion algorithms for biomolecular structure determination using data obtained from both Small-Angle X-Ray Scattering (SAXS) and Single-Particle Electron Microscopy (EM). As a precursor to information fusion, methods for cross-validation to ensure data consistency are first addressed. As such, the theories behind SAXS and EM data acquisition are both reviewed....
Go to contribution page -
Joakim Andén8/9/19, 11:00 AM
A single biological molecule imaged in cryo-EM typically exhibits multiple structural configurations, each with a different function. These configurations may exist along a continuum of states, or conformations, giving rise to a manifold of continuous variability known as the conformational manifold. We propose to estimate this manifold by combining low-resolution reconstruction methods and...
Go to contribution page -
Dr Roy Lederman8/9/19, 11:40 AM
One of the open problems in cryo-EM is mapping complex heterogeneity, such as continuous heterogeneity. We begin our discussion with the question what does it mean to recover a heterogeneous structure, compared to a homogeneous structure or several distinct structures? We introduce “hyper-molecules,” a mathematical formulation which captures the continuum of states and the relationships...
Go to contribution page -
Dr Erik Lindahl8/9/19, 2:00 PM
-
Dr Jasenko Zivanov8/9/19, 2:40 PM
Three new computational methods will be presented that aim to improve the maximal attainable resolution of single-particle cryo-EM reconstructions by measuring and correcting for optical effects in the microscope. All methods work on a given data set, so they can be applied after the images have been collected. The first two methods allow us to measure the symmetrical and antisymmetrical...
Go to contribution page -
Dr Ali Punjani8/9/19, 3:50 PM
Resolution estimation is a critical and practical aspect of cryo-EM reconstruction. In this project, we explore a new way to think about resolution estimation in cryo-EM. We apply the principle of cross-validation as a general idea to develop a framework, from which tasks like resolution estimation can be formulated, and solutions can be derived from first principles. The resulting solutions...
Go to contribution page -
Dr Gabor Herman8/9/19, 4:30 PM
• Tomographic data collection methods (of which cryo-EM is an example) provide us with approximations of line integrals of some parameter.
Go to contribution page
• Reconstruction is the attempted recovery of the distribution of the parameter values from such data.
• The two major categories of reconstruction techniques are:
– transform methods such as weighted backprojection (WBP) and FBP; and
– series expansion... -
Xu Fei (Code Ocean)8/10/19, 9:00 AM
-
8/10/19, 9:00 AM
-
8/10/19, 10:30 AM
-
Chair: Amit Singer
Choose timezone
Your profile timezone: