Rotationally Invariant Image Representation for Viewing Direction Classification in Cryo-EM

We introduce a new rotationally invariant viewing angle classification method for identifying, among a large number of Cryo-EM projection images, similar views without prior knowledge of the molecule. Our rotationally invariant features are based on the bispectrum. Each image is denoised and compressed using steerable principal component analysis (PCA) such that rotating an image is equivalent to phase shifting the expansion coefficients. Thus we are able to extend the theory of bispectrum of 1D periodic signals to 2D images. The randomized PCA algorithm is then used to efficiently reduce the dimensionality of the bispectrum coefficients, enabling fast computation of the similarity between any pair of images. The nearest neighbors provide an initial classification of similar viewing angles. In this way, rotational alignment is only performed for images with their nearest neighbors. The initial nearest neighbor classification and alignment are further improved by a new classification method called vector diffusion maps. Our pipeline for viewing angle classification and alignment is experimentally shown to be faster and more accurate than reference-free alignment with rotationally invariant K-means clustering, MSA/MRA 2D classification, and their modern approximations

Geometry of the ergodic quotient reveals coherent structures in flows

Dynamical systems that exhibit diverse behaviors can rarely be completely understood using a single approach. However, by identifying coherent structures in their state spaces, i.e., regions of uniform and simpler behavior, we could hope to study each of the structures separately and then form the understanding of the system as a whole. The method we present in this paper uses trajectory averages of scalar functions on the state space to: (a) identify invariant sets in the state space, (b) form coherent structures by aggregating invariant sets that are similar across multiple spatial scales. First, we construct the ergodic quotient, the object obtained by mapping trajectories to the space of trajectory averages of a function basis on the state space. Second, we endow the ergodic quotient with a metric structure that successfully captures how similar the invariant sets are in the state space. Finally, we parametrize the ergodic quotient using intrinsic diffusion modes on it. By segmenting the ergodic quotient based on the diffusion modes, we extract coherent features in the state space of the dynamical system. The algorithm is validated by analyzing the Arnold-Beltrami-Childress flow, which was the test-bed for alternative approaches: the Ulam's approximation of the transfer operator and the computation of Lagrangian Coherent Structures. Furthermore, we explain how the method extends the Poincar\'e map analysis for periodic flows. As a demonstration, we apply the method to a periodically-driven three-dimensional Hill's vortex flow, discovering unknown coherent structures in its state space. In the end, we discuss differences between the ergodic quotient and alternatives, propose a generalization to analysis of (quasi-)periodic structures, and lay out future research directions.Comment: Submitted to Elsevier Physica D: Nonlinear Phenomen

Construction of embedded fMRI resting state functional connectivity networks using manifold learning

We construct embedded functional connectivity networks (FCN) from benchmark resting-state functional magnetic resonance imaging (rsfMRI) data acquired from patients with schizophrenia and healthy controls based on linear and nonlinear manifold learning algorithms, namely, Multidimensional Scaling (MDS), Isometric Feature Mapping (ISOMAP) and Diffusion Maps. Furthermore, based on key global graph-theoretical properties of the embedded FCN, we compare their classification potential using machine learning techniques. We also assess the performance of two metrics that are widely used for the construction of FCN from fMRI, namely the Euclidean distance and the lagged cross-correlation metric. We show that the FCN constructed with Diffusion Maps and the lagged cross-correlation metric outperform the other combinations

Structural Variability from Noisy Tomographic Projections

In cryo-electron microscopy, the 3D electric potentials of an ensemble of molecules are projected along arbitrary viewing directions to yield noisy 2D images. The volume maps representing these potentials typically exhibit a great deal of structural variability, which is described by their 3D covariance matrix. Typically, this covariance matrix is approximately low-rank and can be used to cluster the volumes or estimate the intrinsic geometry of the conformation space. We formulate the estimation of this covariance matrix as a linear inverse problem, yielding a consistent least-squares estimator. For $n$ images of size $N$-by-$N$ pixels, we propose an algorithm for calculating this covariance estimator with computational complexity $\mathcal{O}(nN^4+\sqrt{\kappa}N^6 \log N)$, where the condition number $\kappa$ is empirically in the range $10$--$200$. Its efficiency relies on the observation that the normal equations are equivalent to a deconvolution problem in 6D. This is then solved by the conjugate gradient method with an appropriate circulant preconditioner. The result is the first computationally efficient algorithm for consistent estimation of 3D covariance from noisy projections. It also compares favorably in runtime with respect to previously proposed non-consistent estimators. Motivated by the recent success of eigenvalue shrinkage procedures for high-dimensional covariance matrices, we introduce a shrinkage procedure that improves accuracy at lower signal-to-noise ratios. We evaluate our methods on simulated datasets and achieve classification results comparable to state-of-the-art methods in shorter running time. We also present results on clustering volumes in an experimental dataset, illustrating the power of the proposed algorithm for practical determination of structural variability.Comment: 52 pages, 11 figure

Low-shot learning with large-scale diffusion

This paper considers the problem of inferring image labels from images when only a few annotated examples are available at training time. This setup is often referred to as low-shot learning, where a standard approach is to re-train the last few layers of a convolutional neural network learned on separate classes for which training examples are abundant. We consider a semi-supervised setting based on a large collection of images to support label propagation. This is possible by leveraging the recent advances on large-scale similarity graph construction. We show that despite its conceptual simplicity, scaling label propagation up to hundred millions of images leads to state of the art accuracy in the low-shot learning regime

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research