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Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

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.

The development of novel two-dimensional antiferromagnets is crucial for enhancing the performance of spintronic devices. Here, authors realize the synthesis of CrOCl monolayer films and nanosheets that exhibit excellent performance.

Very early observations of a type Ia supernova—from within one hour of explosion—show a red colour that develops and rapidly disappears. These data provide information on the initial explosion mechanism: surface nuclear burning on the white dwarf or extreme mixing of the nuclear burning process.

Lampreys are jawless vertebrates that can offer unique insights into vertebrate evolution. Here they generate a comprehensive cell atlas of the lamprey, uncovering 70 distinct cell types across 14 tissues, and identify pancreas-like cells in the lamprey small intestine.

Unprotected β-fluoroamines are important motifs in synthetic chemistry, offering versatility for the development of β-fluorinated nitrogen-containing compounds. Here, the authors disclose an iron-catalyzed three-component aminofluorination of alkenes using a hydroxylamine reagent and Et3N · 3HF, offering a direct entry to unprotected β-fluoroamines.

Electrochemical CO_x reduction to multi-carbon products is hindered by low energy efficiency, in part due to sluggish ion transport across charge-selective membranes used in electrolysers. Here the authors use a porous, non-charge-selective separator that enhances ion transport and improves performance for CO electrolysis.

An analogue memory built from a two-dimensional material with antimony contacts enables very high, energy-efficient in-memory searches and k-nearest-neighbour classification, offering a scalable, low-power hardware platform for real-time edge artificial intelligence applications.

Hydrogen-doping driven metal to ferroelectric phase transition in a complex oxide NdNiO₃ is demonstrated. Transient negative differential capacitance and implementation of polarization decay into neural network for learning are then presented.

RNA velocity offers insight into cell dynamics but faces key limitations across modalities. Here, authors present GraphVelo, a machine learning framework that refines and extends RNA velocity to multimodal data, enabling quantitative, interpretable cell state transitions.

Inflammasomes are multiprotein complexes, including the protein ASC, that assemble in response to inflammatory stimulation. Here the authors characterise the regulation of ASC during inflammasome formation and show the involvement of SUMOylation and zinc-finger and BTB domain-containing protein 16 (ZBTB16).

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

X. Du, W. Li, G. Li, C. Guo et al. report that dietary galactose regulates the cellular crosstalk between hepatocytes and CD8⁺ T cells via IGFBP-1 production and IGF-1 signalling, thereby modulating T cell exhaustion and antitumour immunity.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Accurate tree cover mapping is vital for fighting climate change and land degradation. This high-resolution study reveals that 17% of pan-tropical tree cover was previously undetected, with over half of recent losses linked to human activities.

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.

Solitons may develop when strain forms at line defects separating commensurate domains in misaligned or lattice-mismatched van der Waals heterostructures. Here, the authors use atomic-force microscopy and nano-infrared spectroscopy to image solitons in thin hBN crystals in the form of long-range periodic superstructures, creating sub-surface hexagonal networks with periods of a few hundred nanometers.

Influenza A HA plasticity often leads to resistant strains that compromise mAb potency as bivalent IgGs. Here, the authors show that engineered IgM molecules overcome this resistance by expanded avidity but still provide potent neutralization and in vivo protection while retaining parental IgG specificity.

C4 photosynthesis serves as a prominent example of convergent evolution in complex traits. Here, the authors construct chromosome-scale genome assemblies for five Flaveria species and investigate the genomic evolution of C4 photosynthesis. Their findings emphasize the roles of retrotransposition and transcriptional regulation in shaping C4 traits.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The SMN protein recognizes symmetric dimethylarginine by its Tudor domain, and SMN deficiency leads to spinal muscular atrophy. Here, Liu et al. discover a small molecule that binds to the SMN Tudor domain and disrupts the interaction between SMN and RNA Polymerase II.

Two genetically linked TdNLR genes from wild emmer wheat are both required for YrTD121-mediated stripe rust resistance. The TdNLR1 and TdNLR2 pair lacks an integrated domain, representing an uncommon architecture for paired NLRs in plants.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The neural mechanisms responsible for cold defense regulation are still unclear. Here, authors show parallel thermogenic pathways from the brain stem to the hypothalamus work together to enable resilience to cold temperature exposure and hypothermia.

A potent mAb shows promise in monkeys either alone or in a combination therapy for either prophylaxis or treatment of infection with SARS-CoV-2 Omicron BA.1, BA.1.1 and BA.2.

In glioma, malignant synapses hijack mechanisms of synaptic plasticity to increase glutamate-dependent currents in tumour cells and the formation of neuron–glioma synapses, thereby promoting tumour proliferation and progression.

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.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Zhou et al. reveal a novel role for brassinosteroids in regulation of vegetative phase change in Arabidopsis. Brassinosteroids regulate this process by simultaneously stabilizing SPL9 and TOE1 through the BIN2-mediated phosphorylation process.

Methane metabolism by some lineages of Archaea contributes to the cycling of carbon on Earth. Here, the authors show high diversity of methyl-coenzyme M reductase (Mcr), a key enzyme associated with archaeal methane/alkane metabolism, in hot spring Archaea, and investigate their ecological roles and evolution.