Research articles

The authors develop the tool RESHAPE to share reference panels in a safer way. The genome–phenome links in reference panels can generate re-identification threats and RESHAPE breaks these links by shuffling haplotypes while preserving imputation accuracy.

MISATO is a database for structure-based drug discovery that combines quantum mechanics data with molecular dynamics simulations on ~20,000 protein–ligand structures. The artificial intelligence models included provide an easy entry point for the machine learning and drug discovery communities.

A method based on a vector-quantized variational autoencoder, called CASTLE, can interpretably extract discrete latent embeddings and quantitatively generate the cell-type-specific feature spectrum for single-cell chromatin accessibility sequencing data.

Cooperation is not merely a dyadic phenomenon, it also includes multi-way social interactions. A mathematical framework is developed to study how the structure of higher-order interactions influences cooperative behavior.

This study introduces SANGO, a method for accurate single-cell annotation leveraging genomic sequences around accessibility peaks within single-cell ATAC sequencing data. SANGO consistently outperforms existing methods across diverse datasets for identification of cell type and detection of unknown tumor cells. SANGO enables the discovery of cell-type-specific functional insights through expression enrichment, cis-regulatory chromatin interactions and motif enrichment analyses.

A fast and versatile three-dimensional cell-based model, called SimuCell3D, is developed for high-resolution simulations of large and complex biological tissues. SimuCell3D natively integrates intra- and extracellular entities, including extracellular matrix, nuclei and polarized cell surfaces.

A method is developed for the directional optimization of multiple properties without prior knowledge on their nature. Using a large ligand dataset, diverse metal complexes are found along the Pareto front of vast chemical spaces.

Andre Berndt and colleagues introduce a machine learning approach to enhance the biophysical characteristics of genetically encoded fluorescent indicators, deriving and testing in vitro new GCaMP mutations that surpass the performance of existing fast GCaMP indicators.

M-OFDFT is a deep learning implementation of orbital-free density functional theory (OFDFT) that achieves DFT-level accuracy on molecular systems with lower cost complexity, and can extrapolate to much larger molecules than those seen during training.

An optimization algorithm is used to discover guest molecules based on knowing only the structure of the host. The molecules are represented as 3D volumes, optimized to improve host–guest interaction and converted into SMILES using a transformer model.

SCORPION is an algorithm to model gene regulatory networks based on single-cell data. The authors show that SCORPION outperforms other methods, accurately detects transcription factor activity and can potentially help with the discovery of disease markers.

kmindex is a tool able to index thousands of environmental metagenomes and perform sequence searches in a fraction of a second, thus enabling real-time queries on complex genomic datasets.

Automated algorithm discovery has been difficult for artificial intelligence given the immense search space of possible functions. Here explainable neural networks are used to discover algorithms that outperform those designed by humans.

The authors introduce two cellular barcoding tools: CellBarcode, for extracting and filtering diverse DNA barcodes from bulk and single-cell sequencing data; and CellBarcodeSim, for simulating barcoding experiments, thus enabling the investigation of the impact of biological and technical factors on barcode detection.

DNA microscopy reconstructs the spatial organization of a sample from a neighborhood graph. In this work, MinIPath efficiently corrects errors from these graphs that distort the reconstruction, both in simulated and experimental data.

The authors develop a general method that combines machine learning and physics to construct macroscopic dynamics directly from microscopic observations, leading to an intuitive understanding of polymer stretching in elongational flow.

A mathematical framework that allows computing the input–output function of neurons with active dendrites reveals how dendrites readily and potently control the response variability, a result that is experimentally confirmed.

EmerGNN, a method to predict interactions for emerging drugs, may improve patient care and drug development by providing insight into the effects of using biomedical networks in interaction predictions.

Using registry data from Denmark, Lehmann et al. create individual-level trajectories of events related to health, education, occupation, income and address, and also apply transformer models to build rich embeddings of life-events and to predict outcomes ranging from time of death to personality.

A diffusion model that generates chemical reactions in 3D with all desired symmetries preserved is established and shown to reduce transition state search from days to seconds and complement intuition-based reaction exploration with generative AI.