Volume 22 Issue 10, October 2025

Awards are gratifying, and also a moment to reflect on how one’s research shapes the work of others.

Studying the gray mouse lemur (Microcebus murinus), one of the world’s smallest primates, in its natural habitat and in the laboratory provides unique perspectives on primate brain evolution, cognition, aging and neurodegenerative diseases, on an accelerated timescale and at a substantially lower cost as compared with larger primate models.

AI-designed binders can enhance prime editing performance by inhibiting the DNA mismatch repair pathway.

Scientists can choose between multiple human genome references, and a pangenome reference is coming. Deciding what to use when is not quite straightforward.

A cryogenic scanning transmission electron microscopy (STEM) approach for analyzing thick biological specimens expands the reach of cryo-electron microscopy.

A new approach sheds light on the biological features learned by protein language models, promising greater interpretability for unsupervised sequence learning.

Targeted deaminase-accessible chromatin sequencing (TDAC-seq) measures chromatin accessibility across long chromatin fibers at targeted loci using double-stranded DNA cytidine deaminases. When combined with pooled CRISPR mutational screening, TDAC-seq enables the high-throughput detection of changes in chromatin accessibility following CRISPR perturbations, allowing fine mapping of sequence–function relationships within endogenous cis-regulatory elements.

Manual analysis of single-molecule time traces is slow and subjective. Now, a transformer-based foundation model — META-SiM —automates key analysis tasks across diverse datasets and enables rapid, systematic discovery of subtle single-molecule behaviors. Application of this approach reveals a previously undetected pre-mRNA splicing intermediate, highlighting its potential to streamline biological discovery.

Graphics processing unit-accelerated MMseqs2 offers tremendous speedups for homology retrieval from metagenomic databases, query-centered multiple sequence alignment generation for structure prediction, and structural searches with Foldseek.

MSnLib is a large-scale, open MSⁿ spectral library featuring >2.3 million MSⁿ and >357,000 MS² spectra for 30,008 unique small molecules.

This study introduces SDR-seq, a droplet-based single-cell DNA–RNA sequencing platform, enabling the study of gene expression profiles linked to both noncoding and coding variants.

This work presents scEpi²-seq, a method for simultaneous single-cell profiling of DNA methylation and histone modifications, enabling direct investigation of the interplay between these two epigenomic marks.

Giotto Suite provides a comprehensive, flexible and scalable platform for technology-agnostic spatial omics analysis using R.

This work presents Spacedust, a tool for de novo identification of conserved gene clusters from metagenomic data.

CORAL can infer the occurrence of rare species based on common species, using DNA metabarcoding data or other high-dimensional biodiversity data. The approach is illustrated on a large-scale biodiversity survey from Madagascar.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

CaCoFold-R3D is a probabilistic model that simultaneously predicts the RNA 3D motifs jointly with the secondary structure in a structural RNA using evolutionary information.

InterPLM is a computational framework to extract and analyze interpretable features from protein language models using sparse autoencoders. By training sparse autoencoders on ESM-2 embeddings, this study identifies thousands of interpretable biological features learned by the different layers of the ESM-2 model.

FlexConsensus is a multi-autoencoder-based algorithm for merging different conformational landscapes from cryogenic electron microscopy heterogeneity analysis into a common latent space for the identification of similarities and differences among various methods. This helps in the validation of estimated conformational landscape and provides tools to streamline the heterogeneity workflow.

precisION discovers, localizes and quantifies protein modifications within complex proteoform assemblies through data-driven analysis of native top-down mass spectra.

Tilt-corrected bright-field scanning transmission electron microscopy offers enhanced cryogenic electron microscopy contrast and substantial improvement in dose efficiency for thick samples such as bacterial cells and large organelles, while still being able to perform single-particle analysis.

META-SiM brings foundation model power to single-molecule time traces, excelling across diverse analysis tasks. Paired with the web-based META-SiM Projector and entropy mapping, it rapidly reveals hidden molecular behaviors inaccessible by other means.

Nimbus, a deep learning model, uses a large multiplexed imaging dataset to predict the likelihood of marker positivity in single cells.

Adaptive optical vision Fourier transformer (AOViFT) is a machine learning-based framework for accurately inferring aberrations and restoring diffraction-limited performance in diverse biological specimens.

Confocal microscopy enables high-resolution, high-plex 3D cyclic immunofluorescence of 30- to 50-µm-thick tissue sections. The approach allows for rich phenotypic assessments of intact cells and intercellular interactions with subcellular resolution.

Squeezed light field microscopy (SLIM) combines ideas from tomography and compressed sensing with light field microscopy to enable volumetric imaging at kilohertz rates, as demonstrated in blood flow imaging in zebrafish and voltage imaging in leeches and mice.

Laser ablation of imaged surface layers under adaptive control enables volumetric imaging of samples consisting of heterogeneous tissues, such as the skull and brain.

HippoMaps provides an open-source resource for studying the human hippocampus at different scales and with different modalities such as histology, fMRI, structural MRI and EEG.