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The first sample of farside lunar soil, collected by Chang’e-6, is strongly cohesive. The high cohesion stems from its fine particle size with intricate shape, probably a result of the high plagioclase abundance and intense meteorite impacts at the sampling site.

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.

Maurizi et al. introduce GraphMetaMat, a graph-based AI framework for designing 3D metamaterials with programmable nonlinear responses, enabling the inverse design of new structural and acoustic behaviours despite fabrication defects and limits.

During poxvirus-induced shutoff, certain cellular and viral mRNAs continue to be translated through distinct modes of non-canonical initiation, in part due to altered ribosome activity, to produce host and viral proteins that support virus spread.

Asteroid interiors are key to understand their formation and evolution. Here, the authors show that numerically simulated low-cohesion and low-friction structures with several high-cohesion internal zones can explain asteroid Bennu’s geophysical characteristics and the absence of the moons.

Liccione et al. report the isolation and characterization of neutralizing antibodies targeting the spike protein of the endemic Alphacoronavirus HCoV-229E.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Crustal permeability evolution predicted from observed MEQs using Bi-LSTM models. MEQ-to-permeability relations confirmed across multiple field data sets using transfer learning with scaling relationships confirmed using physics-based models.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Measuring an individual’s level of exposure to COVID-19 is challenging, and it is therefore unclear whether high exposure may impact immunity. Here, the authors investigate this question using data from a correctional facility in Connecticut, USA, by comparing rates of infection in people who share cells, cellblocks, and with no known exposure.

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.

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.

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.

Earthquake rupture speeds significantly impact seismic hazards. Here, authors report laboratory earthquake experiments reproducing early and stable subEshelby supershear ruptures, and unlocking the correlation between rupture speed and driving load.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Highly potent neutralizing nanobodies (Nbs) are of great interest as potential COVID-19 therapeutics. Here, the authors show that potent neutralizing Nbs targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein are also effective against convergent variants of concern of the virus. They determine eight Nb-bound spike protein cryo-EM structures, classify the binding epitopes of the Nbs and discuss their neutralization mechanisms.

The authors propose Detect, a browser-based anomaly detection framework for diffusion magnetic resonance imaging tractometry data. The tool leverages normative microstructural brain features derived from healthy participants using deep autoencoders to detect anomalies at the individual level.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

Designing efficient, fast and low power consumption phase change memories remains a challenge. Aryana et al. propose a strategy to reduce operating currents by manipulating the interfacial thermal resistance between the phase change unit and the electrodes without incorporating additional insulating layers.

Antibody mediated immunity to SARS-CoV-2 will affect future transmission and disease severity. This systematic review on antibody response to coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and endemic coronaviruses provides insights into kinetics, correlates of protection, and association with disease severity.

Cancer stem cells (CSCs) have important roles in tumour initiation, metastasis and treatment resistance. Here, the authors show that C-terminally phosphorylated p27, together with STAT3, mediates the transcriptional regulation of CSC expansion, increasing cancer formation and metastasis in preclinical breast cancer models.

New antimalarials are urgently needed. Here, the authors identify Open Source Malaria compound, OSMS-106, as a reaction hijacking inhibitor of the malaria parasite protein synthesis machinery, with potential use for treatment and prophylaxis.

Structural analyses of analogues of stable ubiquitin transthiolation intermediates with E1, E2 and E3 enzymes reveal a population of intermediate states that provide insights into the directional transfer of ubiquitin between E1, E2 and E3.

Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.

The synthetic enzyme-armed killer (SEAKER) approach equips chimeric antigen receptor (CAR)-T cells with the capacity to express enzymes that process anticancer prodrugs at tumor sites of action.

Different cells of the tumour microenvironment in HBV-associated human hepatocellular carcinoma (HCC) interact to promote tumour immunity. Here the authors use single cell RNA sequencing to identify TIGIT-NECTIN2 as a pathway by which tumour-associated macrophages reduce intratumour T cell activation.

Aparicio and colleagues identify gene expression changes in breast cancer datasets putatively associated with age-related endocrine effects, suggesting that patient age may influence the prognostic potential of certain biomarkers.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A multiancestry genome-wide association study of chronic alanine aminotransferase elevation identifies candidate risk loci for nonalcoholic fatty liver disease, with replication in external cohorts defined by histology or imaging.

Growing evidence indicates that neutrophils are involved in tumorigenesis, progression and metastasis of hepatocellular carcinoma (HCC). Here, Geh and colleagues summarize neutrophil phenotypes in HCC, describe the pathogenetic mechanisms underlying these contributions of neutrophils to HCC and highlight emerging neutrophil-targeted therapies.