RESUMEN
Advances in cryo-electron tomography (cryo-ET) have produced new opportunities to visualize the structures of dynamic macromolecules in native cellular environments. While cryo-ET can reveal structures at molecular resolution, image processing algorithms remain a bottleneck in resolving the heterogeneity of biomolecular structures in situ. Here, we introduce cryoDRGN-ET for heterogeneous reconstruction of cryo-ET subtomograms. CryoDRGN-ET learns a deep generative model of three-dimensional density maps directly from subtomogram tilt-series images and can capture states diverse in both composition and conformation. We validate this approach by recovering the known translational states in Mycoplasma pneumoniae ribosomes in situ. We then perform cryo-ET on cryogenic focused ion beam-milled Saccharomyces cerevisiae cells. CryoDRGN-ET reveals the structural landscape of S. cerevisiae ribosomes during translation and captures continuous motions of fatty acid synthase complexes inside cells. This method is openly available in the cryoDRGN software.
Asunto(s)
Microscopía por Crioelectrón , Tomografía con Microscopio Electrónico , Procesamiento de Imagen Asistido por Computador , Ribosomas , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Ribosomas/metabolismo , Tomografía con Microscopio Electrónico/métodos , Microscopía por Crioelectrón/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Mycoplasma pneumoniae , Algoritmos , Programas InformáticosRESUMEN
Most current single-cell analysis pipelines are limited to cell embeddings and rely heavily on clustering, while lacking the ability to explicitly model interactions between different feature types. Furthermore, these methods are tailored to specific tasks, as distinct single-cell problems are formulated differently. To address these shortcomings, here we present SIMBA, a graph embedding method that jointly embeds single cells and their defining features, such as genes, chromatin-accessible regions and DNA sequences, into a common latent space. By leveraging the co-embedding of cells and features, SIMBA allows for the study of cellular heterogeneity, clustering-free marker discovery, gene regulation inference, batch effect removal and omics data integration. We show that SIMBA provides a single framework that allows diverse single-cell problems to be formulated in a unified way and thus simplifies the development of new analyses and extension to new single-cell modalities. SIMBA is implemented as a comprehensive Python library ( https://simba-bio.readthedocs.io ).
RESUMEN
Despite much progress in training artificial intelligence (AI) systems to imitate human language, building agents that use language to communicate intentionally with humans in interactive environments remains a major challenge. We introduce Cicero, the first AI agent to achieve human-level performance in Diplomacy, a strategy game involving both cooperation and competition that emphasizes natural language negotiation and tactical coordination between seven players. Cicero integrates a language model with planning and reinforcement learning algorithms by inferring players' beliefs and intentions from its conversations and generating dialogue in pursuit of its plans. Across 40 games of an anonymous online Diplomacy league, Cicero achieved more than double the average score of the human players and ranked in the top 10% of participants who played more than one game.
Asunto(s)
Inteligencia Artificial , Lenguaje , Humanos , Diplomacia , Programas Informáticos , Juegos de VideoRESUMEN
In order to reach human performance on complex visual tasks, artificial systems need to incorporate a significant amount of understanding of the world in terms of macroscopic objects, movements, forces, etc. Inspired by work on intuitive physics in infants, we propose an evaluation benchmark which diagnoses how much a given system understands about physics by testing whether it can tell apart well matched videos of possible versus impossible events constructed with a game engine. The test requires systems to compute a physical plausibility score over an entire video. To prevent perceptual biases, the dataset is made of pixel matched quadruplets of videos, enforcing systems to focus on high level temporal dependencies between frames rather than pixel-level details. We then describe two Deep Neural Networks systems aimed at learning intuitive physics in an unsupervised way, using only physically possible videos. The systems are trained with a future semantic mask prediction objective and tested on the possible versus impossible discrimination task. The analysis of their results compared to human data gives novel insights in the potentials and limitations of next frame prediction architectures.
Asunto(s)
Algoritmos , Benchmarking , Humanos , Aprendizaje , Redes Neurales de la Computación , FísicaRESUMEN
The evaluation of electrostatic energy for a set of point charges in a periodic lattice is a computationally expensive part of molecular dynamics simulations (and other applications) because of the long-range nature of the Coulomb interaction. A standard approach is to decompose the Coulomb potential into a near part, typically evaluated by direct summation up to a cutoff radius, and a far part, typically evaluated in Fourier space. In practice, all decomposition approaches involve approximations-such as cutting off the near-part direct sum-but it may be possible to find new decompositions with improved trade-offs between accuracy and performance. Here, we present the u-series, a new decomposition of the Coulomb potential that is more accurate than the standard (Ewald) decomposition for a given amount of computational effort and achieves the same accuracy as the Ewald decomposition with approximately half the computational effort. These improvements, which we demonstrate numerically using a lipid membrane system, arise because the u-series is smooth on the entire real axis and exact up to the cutoff radius. Additional performance improvements over the Ewald decomposition may be possible in certain situations because the far part of the u-series is a sum of Gaussians and can thus be evaluated using algorithms that require a separable convolution kernel; we describe one such algorithm that reduces communication latency at the expense of communication bandwidth and computation, a trade-off that may be advantageous on modern massively parallel supercomputers.