BioEM: GPU-accelerated computing of Bayesian inference of electron microscopy images

In cryo-electron microscopy (EM), molecular structures are determined from large numbers of projection images of individual particles. To harness the full power of this single-molecule information, we use the Bayesian inference of EM (BioEM) formalism. By ranking structural models using posterior probabilities calculated for individual images, BioEM in principle addresses the challenge of working with highly dynamic or heterogeneous systems not easily handled in traditional EM reconstruction. However, the calculation of these posteriors for large numbers of particles and models is computationally demanding. Here we present highly parallelized, GPU-accelerated computer software that performs this task efficiently. Our flexible formulation employs CUDA, OpenMP, and MPI parallelization combined with both CPU and GPU computing. The resulting BioEM software scales nearly ideally both on pure CPU and on CPU+GPU architectures, thus enabling Bayesian analysis of tens of thousands of images in a reasonable time. The general mathematical framework and robust algorithms are not limited to cryo-electron microscopy but can be generalized for electron tomography and other imaging experiments

Aceleración de algoritmos de procesamiento de imágenes para el análisis de partículas individuales con microscopia electrónica

Tesis Doctoral inédita cotutelada por la Masaryk University (República Checa) y la Universidad Autónoma de Madrid, Escuela Politécnica Superior, Departamento de Ingeniería Informática. Fecha de Lectura: 24-10-2022Cryogenic Electron Microscopy (Cryo-EM) is a vital field in current structural biology. Unlike X-ray crystallography and Nuclear Magnetic Resonance, it can be used to analyze membrane proteins and other samples with overlapping spectral peaks. However, one of the significant limitations of Cryo-EM is the computational complexity. Modern electron microscopes can produce terabytes of data per single session, from which hundreds of thousands of particles must be extracted and processed to obtain a near-atomic resolution of the original sample. Many existing software solutions use high-Performance Computing (HPC) techniques to bring these computations to the realm of practical usability. The common approach to acceleration is parallelization of the processing, but in praxis, we face many complications, such as problem decomposition, data distribution, load scheduling, balancing, and synchronization. Utilization of various accelerators further complicates the situation, as heterogeneous hardware brings additional caveats, for example, limited portability, under-utilization due to synchronization, and sub-optimal code performance due to missing specialization. This dissertation, structured as a compendium of articles, aims to improve the algorithms used in Cryo-EM, esp. the SPA (Single Particle Analysis). We focus on the single-node performance optimizations, using the techniques either available or developed in the HPC field, such as heterogeneous computing or autotuning, which potentially needs the formulation of novel algorithms. The secondary goal of the dissertation is to identify the limitations of state-of-the-art HPC techniques. Since the Cryo-EM pipeline consists of multiple distinct steps targetting different types of data, there is no single bottleneck to be solved. As such, the presented articles show a holistic approach to performance optimization. First, we give details on the GPU acceleration of the specific programs. The achieved speedup is due to the higher performance of the GPU, adjustments of the original algorithm to it, and application of the novel algorithms. More specifically, we provide implementation details of programs for movie alignment, 2D classification, and 3D reconstruction that have been sped up by order of magnitude compared to their original multi-CPU implementation or sufficiently the be used on-the-fly. In addition to these three programs, multiple other programs from an actively used, open-source software package XMIPP have been accelerated and improved. Second, we discuss our contribution to HPC in the form of autotuning. Autotuning is the ability of software to adapt to a changing environment, i.e., input or executing hardware. Towards that goal, we present cuFFTAdvisor, a tool that proposes and, through autotuning, finds the best configuration of the cuFFT library for given constraints of input size and plan settings. We also introduce a benchmark set of ten autotunable kernels for important computational problems implemented in OpenCL or CUDA, together with the introduction of complex dynamic autotuning to the KTT tool. Third, we propose an image processing framework Umpalumpa, which combines a task-based runtime system, data-centric architecture, and dynamic autotuning. The proposed framework allows for writing complex workflows which automatically use available HW resources and adjust to different HW and data but at the same time are easy to maintainThe project that gave rise to these results received the support of a fellowship from the “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/DI18/11660021. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 71367

Advances in xmipp for cryo-electron microscopy: From xmipp to scipion

Xmipp is an open-source software package consisting of multiple programs for processing data originating from electron microscopy and electron tomography, designed and managed by the Biocomputing Unit of the Spanish National Center for Biotechnology, although with contributions from many other developers over the world. During its 25 years of existence, Xmipp underwent multiple changes and updates. While there were many publications related to new programs and functionality added to Xmipp, there is no single publication on the Xmipp as a package since 2013. In this article, we give an overview of the changes and new work since 2013, describe technologies and techniques used during the development, and take a peek at the future of the package

A convolutional autoencoder approach for mining features in cellular electron cryo-tomograms and weakly supervised coarse segmentation

Cellular electron cryo-tomography enables the 3D visualization of cellular organization in the near-native state and at submolecular resolution. However, the contents of cellular tomograms are often complex, making it difficult to automatically isolate different in situ cellular components. In this paper, we propose a convolutional autoencoder-based unsupervised approach to provide a coarse grouping of 3D small subvolumes extracted from tomograms. We demonstrate that the autoencoder can be used for efficient and coarse characterization of features of macromolecular complexes and surfaces, such as membranes. In addition, the autoencoder can be used to detect non-cellular features related to sample preparation and data collection, such as carbon edges from the grid and tomogram boundaries. The autoencoder is also able to detect patterns that may indicate spatial interactions between cellular components. Furthermore, we demonstrate that our autoencoder can be used for weakly supervised semantic segmentation of cellular components, requiring a very small amount of manual annotation.Comment: Accepted by Journal of Structural Biolog