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Understanding interfaces at sub-nanometer scales is vital for complex chemical reactions. Here, the authors advance Pattern-enhanced Resonant Soft X-ray Scattering, enabling efficient operando probing of chemical and structural dynamics at solid-liquid interfaces.

Enhancing the carrier mobility of graphene can enable the investigation of its fundamental properties and promote device applications. Here, the authors report the fabrication of double-layer graphene devices with a quantum mobility up to 10⁷ cm²V⁻¹s⁻¹ and integer quantum Hall features at magnetic fields as low as 0.002 T.

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 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

CellSAM uses an object detector, CellFinder, to detect cells and prompt the Segment Anything Model (SAM) to generate segmentations. This universal model achieves human-level performance across a range of bioimaging data encompassing mammalian cells, yeast and bacteria.

Patients with kidney failure undergoing maintenance hemodialysis have poor long-term survival. Here the authors use affinity-based proteomics to identify circulating risk factors for mortality in patients with kidney failure on hemodialysis.

Duan and Kaushik et al. reveal the structural basis of how Escherichia coli and Thermus thermophilus RNA polymerases initiate transcription from Np₄A alarmones producing Np₄-capped transcripts. The caps form various interactions with a polymerase during initial steps, influencing capping efficiency.

Liver neuroendocrine neoplasms (NEN) without clinically known primary tumor are often classified as primary hepatic NEN. Here, the authors build a classifier accurately predicting the origin sites for NEN based on DNA methylation patterns and show that hepatic NEN with unknown primary tumor are predicted to display a non-hepatic origin.

GTPase-activating proteins (GAPs) often contain regulatory PH domains. In this work, Soubias et al, using an integrated structure-function approach, discovered a mechanism where a GAP PH domain binds directly to a GTPase to induce allosteric changes facilitating GTP hydrolysis.

Garnet-type LLZO electrolytes are considered among the most promising solid-state electrolytes for all-solid-state batteries; however, numerous challenges need to be addressed before they are integrated into a cell. By precipitating amorphous zirconium oxide onto grain boundaries, increased ionic conductivity is observed and dendrite growth is suppressed.

This study shows how Escherichia coli ApaH hydrolyzes enigmatic Np₄N alarmones and decaps Np₄-capped RNAs, thereby impacting their lifetimes. Key features enable ApaH to bind RNA substrates in two orientations, depending on the cap and the first RNA nucleotide.

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.

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.

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.

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.

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.

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.

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.

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.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Palladium-based catalysts are highly effective for the complete oxidation of methane. Here, the authors employ operando transmission electron microscopy, near-ambient pressure X-ray photoelectron spectroscopy, and density functional theory calculations to investigate the active state and catalytic function of Pd nanoparticles in methane oxidation.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

By including small molecules with block copolymers in polymer nanocomposites, various types of nanoparticle can be positioned within the composite with unprecedented precision over several length scales. Moreover, the spatial distribution of nanoparticles within the combined material can be varied by exposure to heat or light, creating a new route to stimuli-responsive materials.

Variants of the 3′−5′ exonuclease TREX1 can cause retinal vasculopathy with cerebral leukoencephalopathy (RVCL). Here, the authors show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and render cells more vulnerable to DNA damage inducing agents.

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.

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.

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.

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.

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

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 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.

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.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Fluid shear stress plays a role in medulloblastoma metastasis through a PIEZO2-actomyosin-GLUT1 signalling cascade.

During herpesvirus infection, most individuals intrinsically suppress a primary infection and therewith preclude potential damage or neurodegeneration of the CNS. Here, Ames et al. show that Optineurin (OPTN), a conserved autophagy receptor, restricts HSV-1 spread, degrades viral VP16 through autophagy and is neuroprotective against HSV infection in vivo.

Nanosized chemical heterogeneities modulate andesitic magma viscosity at early stages of nano-crystallization, according to viscosity models that account for variations in transition metal content

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.

Recently, rich condensed matter physics has emerged from the interplay between band topology and magnetic order. Here, the authors characterize the magnetic Weyl semimetal CeAlGe and find evidence for the role of Weyl fermions in stabilizing the magnetic order above the local transition temperature.

There are currently a lack of genetic models to study the biology of Uterine fibroids (UFs) tumours. Here the authors precisely engineer cells with mutant MED12 Gly-44 and generate myometrial smooth muscle cells (SMCs) that recapitulate major UFs-like cellular, transcriptional, and metabolic alterations.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.