A Geometric Approach for Deciphering Protein Structure from Cryo-EM Volumes

Electron Cryo-Microscopy or cryo-EM is an area that has received much attention in the recent past. Compared to the traditional methods of X-Ray Crystallography and NMR Spectroscopy, cryo-EM can be used to image much larger complexes, in many different conformations, and under a wide range of biochemical conditions. This is because it does not require the complex to be crystallisable. However, cryo-EM reconstructions are limited to intermediate resolutions, with the state-of-the-art being 3.6A, where secondary structure elements can be visually identified but not individual amino acid residues. This lack of atomic level resolution creates new computational challenges for protein structure identification. In this dissertation, we present a suite of geometric algorithms to address several aspects of protein modeling using cryo-EM density maps. Specifically, we develop novel methods to capture the shape of density volumes as geometric skeletons. We then use these skeletons to find secondary structure elements: SSEs) of a given protein, to identify the correspondence between these SSEs and those predicted from the primary sequence, and to register high-resolution protein structures onto the density volume. In addition, we designed and developed Gorgon, an interactive molecular modeling system, that integrates the above methods with other interactive routines to generate reliable and accurate protein backbone models

A Parallel Thinning Algorithm for Grayscale Images

International audienceGrayscale skeletonization offers an interesting alternative to traditional skeletonization following a binarization. It is well known that parallel algorithms for skeletonization outperform sequential ones in terms of quality of results, yet no general and well defined framework has been proposed until now for parallel grayscale thinning. We introduce in this paper a parallel thinning algorithm for grayscale images, and prove its topological soundness based on properties of the critical kernels framework. The algorithm and its proof, given here in the 2D case, are also valid in 3D. Some applications are sketched in conclusion

Intensity-Based Skeletonization of CryoEM Gray-Scale Images Using a True Segmentation-Free Algorithm

Cryo-electron microscopy is an experimental technique that is able to produce 3D gray-scale images of protein molecules. In contrast to other experimental techniques, cryo-electron microscopy is capable of visualizing large molecular complexes such as viruses and ribosomes. At medium resolution, the positions of the atoms are not visible and the process cannot proceed. The medium-resolution images produced by cryo-electron microscopy are used to derive the atomic structure of the proteins in de novo modeling. The skeletons of the 3D gray-scale images are used to interpret important information that is helpful in de novo modeling. Unfortunately, not all features of the image can be captured using a single segmentation. In this paper, we present a segmentation-free approach to extract the gray-scale curve-like skeletons. The approach relies on a novel representation of the 3D image, where the image is modeled as a graph and a set of volume trees. A test containing 36 synthesized maps and one authentic map shows that our approach can improve the performance of the two tested tools used in de novo modeling. The improvements were 62 and 13 percent for Gorgon and DP-TOSS, respectively

3D + t Morphological Processing: Applications to Embryogenesis Image Analysis

We propose to directly process 3D + t image sequences with mathematical morphology operators, using a new classi?cation of the 3D+t structuring elements. Several methods (?ltering, tracking, segmentation) dedicated to the analysis of 3D + t datasets of zebra?sh embryogenesis are introduced and validated through a synthetic dataset. Then, we illustrate the application of these methods to the analysis of datasets of zebra?sh early development acquired with various microscopy techniques. This processing paradigm produces spatio-temporal coherent results as it bene?ts from the intrinsic redundancy of the temporal dimension, and minimizes the needs for human intervention in semi-automatic algorithms

Skeletonization methods for image and volume inpainting

Image and shape restoration techniques are increasingly important in computer graphics. Many types of restoration techniques have been proposed in the 2D image-processing and according to our knowledge only one to volumetric data. Well-known examples of such techniques include digital inpainting, denoising, and morphological gap filling. However efficient and effective, such methods have several limitations with respect to the shape, size, distribution, and nature of the defects they can find and eliminate. We start by studying the use of 2D skeletons for the restoration of two-dimensional images. To this end, we show that skeletons are useful and efficient for volumetric data reconstruction. To explore our hypothesis in the 3D case, we first overview the existing state-of-the-art in 3D skeletonization methods, and conclude that no such method provides us with the features required by efficient and effective practical usage. We next propose a novel method for 3D skeletonization, and show how it complies with our desired quality requirements, which makes it thereby suitable for volumetric data reconstruction context. The joint results of our study show that skeletons are indeed effective tools to design a variety of shape restoration methods. Separately, our results show that suitable algorithms and implementations can be conceived to yield high end-to-end performance and quality of skeleton-based restoration methods. Finally, our practical applications can generate competitive results when compared to application areas such as digital hair removal and wire artifact removal

Rapid, Reliable Tissue Fractionation Algorithm for Commercial Scale Biorefineries

Increasing demand, limited supply, and the impact on the environment raise significant concerns about the consumption of fossil fuels. Because of this, global economies are facing two significant energy challenges: i) securing the supply of reliable and affordable energy and ii) achieving the transformation to a low-carbon, high-efficiency, and sustainable energy system. Recently, there has been growing interest in developing portable transportation fuels from biomass in order to reduce the petroleum consumption in the transportation sector - a major contributor to greenhouse gas emission. A cost-effective conversion process to produce biofuels from lignocellulosic biomass material relies not just on the material quality, but also on the biorefinery’s ability to measure the quality of the source biomass. The quality of the feedstock is crucial for a commercially viable conversion platform. This research mainly focuses on developing sensing techniques using 3D X-ray imaging to study quality factors like material composition, ash content and moisture content which affect the conversion efficiency, equipment wear, and product yield in the bioethanol production in a real-time or near real-time basis

Free-form image registration of human cochlear μCT data using skeleton similarity as anatomical prior

AbstractBetter understanding of the anatomical variability of the human cochlear is important for the design and function of Cochlear Implants. Proper non-rigid alignment of high-resolution cochlear μCT data is a challenge for the typical cubic B-spline registration model. In this paper we study one way of incorporating skeleton-based similarity as an anatomical registration prior. We extract a centerline skeleton of the cochlear spiral, and generate corresponding parametric pseudo-landmarks between samples. These correspondences are included in the cost function of a typical cubic B-spline registration model to provide a more global guidance of the alignment. The resulting registrations are evaluated using different metrics for accuracy and model behavior, and compared to the results of a registration without the prior

Transient Study of the Wetting Films in Porous Media Using 3D X-Ray Computed Micro-Tomography: Effect of Imbibition Rate and Pore Geometry

Imbibition in porous media is governed by the complex interplay between viscous and capillary forces, pore structure and fluid properties. Understanding and predicting imbibition is important in many natural and engineered applications; it affects the efficiency of oil production operations, the moisture and contaminant transport in soil science, and the formation of defects in certain types of composite materials. Majority of the studies published on the transient imbibition behavior in a porous medium were conducted in the simplified 2D transparent micromodels or the 2D projection visualization (X-ray or visible light) of the 3D porous medium. However, the pore level transient imbibition studies have not been reported on real three dimensional porous medium. The main challenge arises from the slowness of the present 3D imaging techniques in comparison with the speed of the pore filling events. To overcome these difficulties, we have developed a novel experimental technique using UV-induced polymerization, which allows the fluid phase distributions to be frozen in place during transient imbibition. Pore-scale structure of the front can then be examined in the 3D microscopic details using the X-ray Computed micro-Tomography (XCT). We have also developed a suite of advanced image segmentation programs to segment the grayscale XCT data. Image-based physically representative pore network generation techniques were unitized to quantify the geometry and topology of pore, wetting and nonwetting phase structure. Using UV initiated polymerization technique and image-based quantitative analysis tools; we have studied the effects of capillary number, pore structure and surface roughness on the structure of the transient imbibition front