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PhenoMol integrates graph theory and biological knowledge to reduce multi-omic dimensionality, predict phenotypes, and reveal causal patterns. It outperforms conventional models that lack biological constraints and is openly available for health, performance, and disease research.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Strings of local excitations are interesting features of a strongly correlated topological quantum matter. Here, the authors show that Boltzmann-distributed strings of local excitations also describe the topological physics of the Santa Fe geometry of artificial spin ice, which is a classical thermal system.

Intense lasers enable scientists to study the behaviour of matter under extreme pressures, but obtaining information about its atomic structure is challenging. In this work, Suggit et al. demonstrate the use of white-light X-ray diffraction to probe the structure of laser-shocked copper on nanosecond timescales.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

The first experimental demonstration of saturable absorption in core-electron transitions in aluminium paves the way for investigating warm dense matter, which potentially has an important role in planetary science and the realization of inertial confinement fusion.

Despite evidence for an ice-rich outer shell, little water ice has been observed on the surface of Ceres. Lobate morphologies observed on Ceres that are increasingly prevalent towards the dwarf planet’s poles are consistent with ice-rich flows.

Insights into the mechanism of methylthio-alkane reductase (MAR)—a nitrogenase-like enzyme essential for growth under sulfate-limited conditions—have remained scarce. Now a cryo-EM structure of MAR from Rhodospirillum rubrum, along with spectroscopic investigations, reveals how it uses complex metallocofactors for catalysis.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

Long-range order is normally related to an entropy decrease. Yet, an increase in entropy in one part of a system can induce long-range order in another. A new form of such entropy-driven order is now demonstrated in an artificial spin-ice system.

Non-fullerene acceptors are crucial for realising efficient charge transport and high power conversion in organic solar cells, yet the relationship of molecular packing and carrier transport is not well-understood. Here, the authors study the effect of side-chain engineering on the backbone assembly and the corresponding charge transport pathway.

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

An analysis of T cell responses in people with amyotrophic lateral sclerosis shows that the C9orf72 antigen is a key target of autoimmune responses in the disease, and identifies C9orf72 epitopes that are recognized.

A clinical trial using continuous glucose monitoring found that a Dietary Approaches to Stop Hypertension (DASH)-style diet tailored for diabetes reduced hyperglycemia and improved glucose control compared to a typical American diet in patients with type 2 diabetes.

mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the microbiome.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Forward-biased bipolar membranes (FB-BPMs), which recover potential from pH gradients through ion–ion recombination, show promise for application in sustainable devices. The authors use physics-based modeling to elucidate how ion-specific phenomena dictate performance, reveal how selective ion management can mitigate energy losses and provide insights into the rational design of next-generation FB-BPMs.

New approaches are required to access metal-organic assemblies with unusual structural properties. Here, the authors use an in situ redox reaction to obtain a mixed-valence, Mn(II)/Mn(III)-containing metal-organic nanocapsule with an odd number of metal ions.

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

Observations from a borehole in the Kamb Ice Stream suggest that discrete subglacial discharge events dominate channel melt and sediment transport.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Systematic base-editing and computational screens identify specific cysteine residues on VPS35 in the retromer complex as key sensors that decrease mitochondrial translation in response to reactive oxygen species signals.

Video microscopy is key in studying cell migration, but accomplishing this in a high-throughput manner is still challenging. Here, the authors present an array microscope that can track the movements of thousands of individual cells simultaneously, and that can be used for drug screening studies.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The physics of Mott insulators is obscured by the interplay between competing orders and fluctuations. Here, the authors track the evolution of the electronic structure of Mott insulator strontium iridate as the iridium atoms are replaced by rhodium, providing insight into this exotic state of matter.

A study describes an approach using designed building blocks that are far more regular in geometry than natural proteins to construct modular multicomponent protein assemblies.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

There are large uncertainties in wind-wave climate projections that need to be resolved to allow adaptation planning. A multi-method ensemble of global wave climate projections shows robust changes in wave height, period and direction that put 50% of the global coast at risk.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.