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HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

Oby, Degenhart, Grigsby and colleagues used a brain–computer interface to challenge monkeys to override their natural time courses of neural activity. They found the time courses to be highly robust, suggestive of network-level computational mechanisms.

An automatic framework, SNOPS, is developed for configuring a spiking network model to reproduce neuronal recordings. It is used to discover previously unknown limitations of spiking network models, thereby guiding model development.

Design choices for dimensionality reduction on calcium imaging recordings are systematically evaluated, and a method called calcium imaging linear dynamical system (CILDS) is proposed for performing deconvolution and dimensionality reduction jointly.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

Mass spectrometry (MS) enables identification of modified RNA residues, but high-throughput processing is currently a bottleneck. Here, the authors present a free and open-source database search engine for RNA MS data to facilitate reliable identification of modified RNA sequences.

A dimensionality reduction framework, delayed latents across groups (DLAG), is proposed for disentangling the concurrent flow of signals between populations of neurons. DLAG reveals bidirectional communication between visual cortical areas.

Hennig et al. study how changes in internal state interact with learning in primates. They report stereotyped activity fluctuations in the motor cortex that reflect the animal’s level of engagement and predict how quickly the animals learned.

How cortical areas interact via feedforward and feedback signaling remains unclear. Here, the authors recorded from V1 and V2/V4 in macaque visual cortex and found that feedforward and feedback interactions vary with stimulus drive and involve different neuronal population activity patterns.

Neural activity residing in a low-dimensional space that reflects specific correlation patterns among neurons can be used to maintain the performance of brain–computer interfaces in the presence of recording instabilities.

Although action and motor imagery share similar population-wide neural responses in motor cortex, a subset of those responses exists in orthogonal action-unique and imagery-unique subspaces.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

The authors measured the variability of neuronal responses across a large number of datasets and cortical areas. They found that variability decreased in response to all stimuli tested, whether the animal was awake, behaving or anesthetized, suggesting that the stabilization of cortex in response to an input is a general cortical property.

Learning is ubiquitous in everyday life, yet it is unclear how neurons change their activity together during learning. Golub and colleagues show that short-term learning relies on a fixed neural repertoire, which limits behavioral improvement.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

Attention affects stimulus response gain, but its impact without sensory drive is less known. Here, the authors show that attention is coded diversely in a population and is distinct between unstimulated and stimulated contexts, providing a contrast to normalized gain models of attention.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

A new type of brain–machine interface device enables recording of neural activity in the monkey cortex and extraction of intended target signals, leaving the monkey able to place a cursor on a location, just by thinking about it.

Breeding has increased crop productivity, but whether it has also changed phenotypic plasticity is unclear. Here, the authors find maize genomic regions selected for high productivity show reduced contribution to genotype by environment variation and provide evidence for regulatory control of phenotypic stability.

The mechanisms of action of proteasome inhibitors (PI) in multiple myeloma (MM) treatment are not fully elucidated. Here, the authors use unbiased phosphoproteomics in PI-treated MM and show increased phosphorylation of splicing-associated proteins, ultimately revealing splicing interference as a mode of PI action as well as demonstrating the spliceosome as a specific therapeutic vulnerability in this disease.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

Brain-computer interfaces (BCIs) and optical imaging have both undergone impressive technological growth in recent years. A study in which mice learn to modulate neural activity merges these technologies to investigate the neural basis of BCI learning with unprecedented spatial detail.

The HPN-DREAM community challenge assessed the ability of computational methods to infer causal molecular networks, focusing specifically on the task of inferring causal protein signaling networks in cancer cell lines.

During learning, the new patterns of neural population activity that develop are constrained by the existing network structure so that certain patterns can be generated more readily than others.

The type III secretion system (T3SS) of pathogenic bacteria is composed of a series of rings in the inner and outer bacterial membranes. Crystallographic studies of EscJ and PrgH, proteins that comprise the two inner membrane rings of the T3SS, suggest that a conserved structural motif serves as a platform for ring assembly. Additional docking and modeling studies reveal details of the T3SS architecture and assembly.

If stored information is erased from neural circuits in one brain hemisphere in mice, the lost data can be recovered from the other. This finding highlights a safeguarding mechanism at work in the brain. See Article p.459

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Cataloging microbial genomes from Earth’s environments expands the known phylogenetic diversity of bacteria and archaea.

The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

Current neural prostheses can translate neural activity into control signals for guiding prosthetic devices, but poor performance limits practical application. Here the authors present a new cursor-control algorithm that approaches native arm control speed and accuracy, permits sustained uninterrupted use for hours, generalizes to more challenging tasks and provides repeatable high performance for years after implantation, thereby increasing the clinical viability of neural prostheses.

A cognitive brain machine interface that continuously tracks momentary changes in electrophysiological steady-state visually evoked potentials (SSVEPs) in real-time provides a reliable readout of attentional state in humans.

A longitudinal study in mice reveals that a booster dose of mRNA vaccine BNT162b2 enhances humoral and cell-mediated responses and provides sterilizing immunity against Omicron-induced lung infection in aged animals.

Many recent studies have adopted dimensionality reduction to analyze neural population activity and to find features that are not apparent at the level of individual neurons. The authors describe the scientific motivation for population analyses and the dimensionality reduction methods commonly applied to population activity. They also offer practical advice about selecting methods and interpreting their outputs.