The ENL metric measures the smoothness in the homogeneous regions.

It consists of reconstructing a 3D tomogram from captured 2D projections of the scanned sample.

The ENL metric measures the smoothness in the homogeneous regions.

The past decade has witnessed a transformative "cryoEM revolution" characterized by exponential growth in high - resolution structural data, driven by advances in cryogenic electron microscopy (cryoEM) and cryogenic electron t omography (cryoET). The integration of deep learning technologies into structural proteomics workflows has emerged as a pivotal force in addressing longstanding challenges, including low signal - to - noise ratios, preferred orientation artifacts, and missing - wedge problems th at have historically limited efficiency and scalability. This review article examines the application of Artificial Intelligence (AI) across the entire cryoEM pipeline, from automated particle picking using convolutional neural networks (Topaz, crYOLO, Cry oSegNet) to computational solutions for preferred orientation bias (spIsoNet, cryoPROS) and advanced denoising algorithms (Topaz - Denoise). In cryoET, tools such as IsoNet employ U - Net architectures for simultaneous missing - wedge correction and noise reduct ion, while TomoNet streamlines subtomogram averaging through AI - driven particle detection. The workflow culminates with automated atomic model building using sophisticated tools like ModelAngelo, DeepTracer, and CryoREAD that translate density maps into in terpretable biological structures. These AI - enhanced approaches have demonstrated remarkable achievements, including near - atomic resolution reconstructions with minimal manual intervention, resolution of previously intractable datasets suffering from sever e orientation bias, and successful application to diverse biological systems from HIV virus - like particles to in situ ribosomal complexes. As deep learning continues to evolve, particularly with the emergence of large language models and vision transformer s, the future promises even more sophisticated automation and accessibility in structural biology, potentially revolutionizing our understanding of macromolecular architecture and function.

Cryo-electron tomography (cryo-ET) has emerged as a powerful technique for imaging macromolecular complexes in their near-native states. However, the localization of 3D particles in cellular environments still presents a significant challenge due to low signal-to-noise ratios and missing wedge artifacts. Deep learning approaches have shown great potential, but they need huge amounts of data, which can be a challenge in cryo-ET scenarios where labeled data is often scarce. In this paper, we propose a novel Self-augmented and Self-interpreted (SaSi) deep learning approach towards few-shot particle detection in 3D cryo-ET images. Our method builds upon self-augmentation techniques to further boost data utilization and introduces a self-interpreted segmentation strategy for alleviating dependency on labeled data, hence improving generalization and robustness. As demonstrated by experiments conducted on both simulated and real-world cryo-ET datasets, the SaSi approach significantly outperforms existing state-of-the-art methods for particle localization. This research increases understanding of how to detect particles with very few labels in cryo-ET and thus sets a new benchmark for few-shot learning in structural biology.

Cryogenic electron tomography (cryo-ET) is a technique for imaging biological samples such as viruses, cells, and proteins in 3D. A microscope collects a series of 2D projections of the sample, and the goal is to reconstruct the 3D density of the sample called the tomogram. This is difficult as the 2D projections have a missing wedge of information and are noisy. Tomograms reconstructed with conventional methods, such as filtered back-projection, suffer from the noise, and from artifacts and anisotropic resolution due to the missing wedge of information. To improve the visual quality and resolution of such tomograms, we propose a deep-learning approach for simultaneous denoising and missing wedge reconstruction called DeepDeWedge. DeepDeWedge is based on fitting a neural network to the 2D projections with a self-supervised loss inspired by noise2noise-like methods. The algorithm requires no training or ground truth data. Experiments on synthetic and real cryo-ET data show that DeepDeWedge achieves competitive performance for deep learning-based denoising and missing wedge reconstruction of cryo-ET tomograms.

We review four types of algorithms for physics-informed machine learning (PIML) inversion of geophysical data. The unifying equation is given by the joint objective function $\epsilon$: \begin{eqnarray} \epsilon^{||-PIML}&=&\lambda_1 \overbrace{||{\bf W}^{ML}({\bf H}_{{\bf w}} {\bf d}^{obs}-{\bf m})||^2}^{NN} + \lambda_2 \overbrace{{||{\bf W}^{FWI}({\bf L} {\bf m}-{\bf d}^{obs})||^2}}^{FWI} ~+ \nonumber\\ \nonumber\\ && + ~~Regularizer, \label{PIML.eq120} \end{eqnarray}where the optimal model ${\bf m}^*$ and weights $\bf w^*$ minimize $\epsilon$. Here, The matrix weights are given by the boldface symbol $\bf W$, and full waveform inversion (FWI) is typically computed using a finite-difference solution of the wave equation, where $\bf L$ represents the forward modeling operation of the wave equation as a function of the model $\bf m$. Also, a fully-connected neural network (NN) is used to compute the model ${\bf H_w}{\bf d}^{obs} \approx \bf m$ from the observed input data ${\bf d}^{obs}$. The selection of weights $\lambda_i$ and the NN operations determine one of four different PIML algorithms. PIML offers potential advantages over standard FWI through its enhanced ability to avoid local minima and the option to locally train the inversion operator, minimizing the requirement for extensive training data for global applicability. However, the effectiveness of PIML relies on the similarity between the test and trained data. Nevertheless, a possible strategy to overcome this limitation involves initial pretraining of a PIML architecture with data from a broader region, followed by fine-tuning for specific data-a method reminiscent of the way large language models are pretrained and adapted for various tasks.

Particle localization and -classification constitute two of the most fundamental problems in computational microscopy. In recent years, deep learning based approaches have been introduced for these tasks with great success. A key shortcoming of these supervised learning methods is their need for large training data sets, typically generated from particle models in conjunction with complex numerical forward models simulating the physics of transmission electron microscopes. Computer implementations of such forward models are computationally extremely demanding and limit the scope of their applicability. In this paper we propose a method for simulating the forward operator of an electron microscope based on additive noise and Neural Style Transfer techniques. We evaluate the method on localization and classification tasks using one of the established state-of-the-art architectures showing performance on par with the benchmark. In contrast to previous approaches, our method accelerates the data generation process by a factor of 750 while using 33 times less memory and scales well to typical transmission electron microscope detector sizes. It utilizes GPU acceleration and parallel processing. It can be used to adapt a synthetic training data set according to reference data from any transmission electron microscope. The source code is available at https://gitlab.com/deepet/faket.

The statistical supervised learning framework assumes an input-output set with a joint probability distribution that is reliably represented by the training dataset. The learner is then required to output a prediction rule learned from the training dataset's input-output pairs. In this work, we provide meaningful insights into the asymptotic equipartition property (AEP) \citep{Shannon:1948} in the context of machine learning, and illuminate some of its potential ramifications for few-shot learning. We provide theoretical guarantees for reliable learning under the information-theoretic AEP, and for the generalization error with respect to the sample size. We then focus on a highly efficient recurrent neural net (RNN) framework and propose a reduced-entropy algorithm for few-shot learning. We also propose a mathematical intuition for the RNN as an approximation of a sparse coding solver. We verify the applicability, robustness, and computational efficiency of the proposed approach with image deblurring and optical coherence tomography (OCT) speckle suppression. Our experimental results demonstrate significant potential for improving learning models' sample efficiency, generalization, and time complexity, that can therefore be leveraged for practical real-time applications.