EMinsight: a tool to capture cryoEM microscope configuration and experimental outcomes for analysis and deposition.

The widespread adoption of cryoEM technologies for structural biology has pushed the discipline to new frontiers. A significant worldwide effort has refined the single-particle analysis (SPA) workflow into a reasonably standardized procedure. Significant investments of development time have been made, particularly in sample preparation, microscope data-collection efficiency, pipeline analyses and data archiving. The widespread adoption of specific commercial microscopes, software for controlling them and best practices developed at facilities worldwide has also begun to establish a degree of standardization to data structures coming from the SPA workflow. There is opportunity to capitalize on this moment in the maturation of the field, to capture metadata from SPA experiments and correlate the metadata with experimental outcomes, which is presented here in a set of programs called EMinsight. This tool aims to prototype the framework and types of analyses that could lead to new insights into optimal microscope configurations as well as to define methods for metadata capture to assist with the archiving of cryoEM SPA data. It is also envisaged that this tool will be useful to microscope operators and facilities looking to rapidly generate reports on SPA data-collection and screening sessions.

Triple-kernel gated attention-based multiple instance learning with contrastive learning for medical image analysis.

In machine learning, multiple instance learning is a method evolved from supervised learning algorithms, which defines a "bag" as a collection of multiple examples with a wide range of applications. In this paper, we propose a novel deep multiple instance learning model for medical image analysis, called triple-kernel gated attention-based multiple instance learning with contrastive learning. It can be used to overcome the limitations of the existing multiple instance learning approaches to medical image analysis. Our model consists of four steps. i) Extracting the representations by a simple convolutional neural network using contrastive learning for training. ii) Using three different kernel functions to obtain the importance of each instance from the entire image and forming an attention map. iii) Based on the attention map, aggregating the entire image together by attention-based MIL pooling. iv) Feeding the results into the classifier for prediction. The results on different datasets demonstrate that the proposed model outperforms state-of-the-art methods on binary and weakly supervised classification tasks. It can provide more efficient classification results for various disease models and additional explanatory information.

Parameter inversion of a polydisperse system in small-angle scattering.

A general method to invert parameter distributions of a polydisperse system using data acquired from a small-angle scattering (SAS) experiment is presented. The forward problem, i.e. calculating the scattering intensity given the distributions of any causal parameters of a theoretical model, is generalized as a multi-linear map, characterized by a high-dimensional Green tensor that represents the complete scattering physics. The inverse problem, i.e. finding the maximum-likelihood estimation of the parameter distributions (in free form) given the scattering intensity (either a curve or an image) acquired from an experiment, is formulated as a constrained nonlinear programming (NLP) problem. This NLP problem is solved with high accuracy and efficiency via several theoretical and computational enhancements, such as an automatic data scaling for accuracy preservation and GPU acceleration for large-scale multi-parameter systems. Six numerical examples are presented, including both synthetic tests and solutions to real neutron and X-ray data sets, where the method is compared with several existing methods in terms of their generality, accuracy and computational cost. These examples show that SAS inversion is subject to a high degree of non-uniqueness of solution or structural ambiguity. With an ultra-high accuracy, the method can yield a series of near-optimal solutions that fit data to different acceptable levels.

Keyhole fluctuation and pore formation mechanisms during laser powder bed fusion additive manufacturing.

Keyhole porosity is a key concern in laser powder-bed fusion (LPBF), potentially impacting component fatigue life. However, some keyhole porosity formation mechanisms, e.g., keyhole fluctuation, collapse and bubble growth and shrinkage, remain unclear. Using synchrotron X-ray imaging we reveal keyhole and bubble behaviour, quantifying their formation dynamics. The findings support the hypotheses that: (i) keyhole porosity can initiate not only in unstable, but also in the transition keyhole regimes created by high laser power-velocity conditions, causing fast radial keyhole fluctuations (2.5-10 kHz); (ii) transition regime collapse tends to occur part way up the rear-wall; and (iii) immediately after keyhole collapse, bubbles undergo rapid growth due to pressure equilibration, then shrink due to metal-vapour condensation. Concurrent with condensation, hydrogen diffusion into the bubble slows the shrinkage and stabilises the bubble size. The keyhole fluctuation and bubble evolution mechanisms revealed here may guide the development of control systems for minimising porosity.

Entropy-based active learning of graph neural network surrogate models for materials properties.

Graph neural networks trained on experimental or calculated data are becoming an increasingly important tool in computational materials science. Networks once trained are able to make highly accurate predictions at a fraction of the cost of experiments or first-principles calculations of comparable accuracy. However, these networks typically rely on large databases of labeled experiments to train the model. In scenarios where data are scarce or expensive to obtain, this can be prohibitive. By building a neural network that provides confidence on the predicted properties, we are able to develop an active learning scheme that can reduce the amount of labeled data required by identifying the areas of chemical space where the model is most uncertain. We present a scheme for coupling a graph neural network with a Gaussian process to featurize solid-state materials and predict properties including a measure of confidence in the prediction. We then demonstrate that this scheme can be used in an active learning context to speed up the training of the model by selecting the optimal next experiment for obtaining a data label. Our active learning scheme can double the rate at which the performance of the model on a test dataset improves with additional data compared to choosing the next sample at random. This type of uncertainty quantification and active learning has the potential to open up new areas of materials science, where data are scarce and expensive to obtain, to the transformative power of graph neural networks.

Assessment of protein-protein interfaces in cryo-EM derived assemblies.

Structures of macromolecular assemblies derived from cryo-EM maps often contain errors that become more abundant with decreasing resolution. Despite efforts in the cryo-EM community to develop metrics for map and atomistic model validation, thus far, no specific scoring metrics have been applied systematically to assess the interface between the assembly subunits. Here, we comprehensively assessed protein-protein interfaces in macromolecular assemblies derived by cryo-EM. To this end, we developed Protein Interface-score (PI-score), a density-independent machine learning-based metric, trained using the features of protein-protein interfaces in crystal structures. We evaluated 5873 interfaces in 1053 PDB-deposited cryo-EM models (including SARS-CoV-2 complexes), as well as the models submitted to CASP13 cryo-EM targets and the EM model challenge. We further inspected the interfaces associated with low-scores and found that some of those, especially in intermediate-to-low resolution (worse than 4 Å) structures, were not captured by density-based assessment scores. A combined score incorporating PI-score and fit-to-density score showed discriminatory power, allowing our method to provide a powerful complementary assessment tool for the ever-increasing number of complexes solved by cryo-EM.

Interpretable, calibrated neural networks for analysis and understanding of inelastic neutron scattering data.

Deep neural networks (NNs) provide flexible frameworks for learning data representations and functions relating data to other properties and are often claimed to achieve 'super-human' performance in inferring relationships between input data and desired property. In the context of inelastic neutron scattering experiments, however, as in many other scientific scenarios, a number of issues arise: (i) scarcity of labelled experimental data, (ii) lack of uncertainty quantification on results, and (iii) lack of interpretability of the deep NNs. In this work we examine approaches to all three issues. We use simulated data to train a deep NN to distinguish between two possible magnetic exchange models of a half-doped manganite. We apply the recently developed deterministic uncertainty quantification method to provide error estimates for the classification, demonstrating in the process how important realistic representations of instrument resolution in the training data are for reliable estimates on experimental data. Finally we use class activation maps to determine which regions of the spectra are most important for the final classification result reached by the network.

A Multilane Tracking Algorithm Using IPDA with Intensity Feature.

Detection of multiple lane markings on road surfaces is an important aspect of autonomous vehicles. Although a number of approaches have been proposed to detect lanes, detecting multiple lane markings, particularly across a large number of frames and under varying lighting conditions, in a consistent manner is still a challenging problem. In this paper, we propose a novel approach for detecting multiple lanes across a large number of frames and under various lighting conditions. Instead of resorting to the conventional approach of processing each frame to detect lanes, we treat the overall problem as a multitarget tracking problem across space and time using the integrated probabilistic data association filter (IPDAF) as our basis filter. We use the intensity of the pixels as an augmented feature to correctly group multiple lane markings using the Hough transform. By representing these extracted lane markings as splines, we then identify a set of control points, which becomes a set of targets to be tracked over a period of time, and thus across a large number of frames. We evaluate our approach on two different fronts, covering both model- and machine-learning-based approaches, using two different datasets, namely the Caltech and TuSimple lane detection datasets, respectively. When tested against model-based approach, the proposed approach can offer as much as 5%, 12%, and 3% improvements on the true positive, false positive, and false positives per frame rates compared to the best alternative approach, respectively. When compared against a state-of-the-art machine learning technique, particularly against a supervised learning method, the proposed approach offers 57%, 31%, 4%, and 9× improvements on the false positive, false negative, accuracy, and frame rates. Furthemore, the proposed approach retains the explainability, or in other words, the cause of actions of the proposed approach can easily be understood or explained.

A Novel Method for Sea-Land Clutter Separation Using Regularized Randomized and Kernel Ridge Neural Networks.

Classification of clutter, especially in the context of shore based radars, plays a crucial role in several applications. However, the task of distinguishing and classifying the sea clutter from land clutter has been historically performed using clutter models and/or coastal maps. In this paper, we propose two machine learning, particularly neural network, based approaches for sea-land clutter separation, namely the regularized randomized neural network (RRNN) and the kernel ridge regression neural network (KRR). We use a number of features, such as energy variation, discrete signal amplitude change frequency, autocorrelation performance, and other statistical characteristics of the respective clutter distributions, to improve the performance of the classification. Our evaluation based on a unique mixed dataset, which is comprised of partially synthetic clutter data for land and real clutter data from sea, offers improved classification accuracy. More specifically, the RRNN and KRR methods offer 98.50% and 98.75% accuracy, outperforming the conventional support vector machine and extreme learning based solutions.