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Using large-scale genetics and Genomic SEM/E-SEM, the study shows broad shared genetic risk between many physical illnesses and internalizing, neurodevelopmental, and substance-use disorders, revealing a transdiagnostic illness factor and cross-cutting disease pathways.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The growing demand for rare earth elements (REEs) underscores the need for sustainable recovery methods and a reliable supply. Here the authors establish a platform using a yeast to produce bio-oxalic acid for REE recovery, achieving 99% REE recovery from low-grade ore.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Biochemical, behavioural, electrophysiological, and spine analyses show that female APP/PS1 mice have reduced PSD-95 palmitoylation as well as memory and synaptic deficits. Palm B treatment rescued these impairments, revealing a potential AD therapy.

A nine-year transit-timing campaign has measured the extremely low masses and densities of four large planets orbiting the young star V1298 Tau, which are now predicted to contract and form a typical compact super-Earth and sub-Neptune 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.

Radical Fe^II/α-ketoglutarate-dependent halogenases are powerful biocatalysts for C–H functionalization. Here, the authors reveal the mechanistic basis for chemoselectivity in a lysine halogenase.

Natural products and their synthesis have always fascinated organic chemists, frequently providing the inspiration and testing ground for new synthetic methods. This Review considers examples of natural products that were prepared first synthetically and predicted to be natural products prior to their isolation from nature.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

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.

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.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

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.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

This study builds a facility-level cost model to assess U.S. cathode material costs, showing that all-domestic supply is 9–34% costlier than global average, increasing by cobalt content, while these shortfalls can be overcome by selective low-cost material imports.

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 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.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

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.

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.

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.

The advances in artificial intelligence are permeating most scientific domains, and heterogeneous catalysis is no exception. This Perspective discusses the current state and future prospects of AI in heterogeneous catalysis, from the development of an AI-ready data ecosystem to multimodal foundation models and autonomous labs.

Andrew M. Sessler, Director of the Lawrence Berkeley Laboratory (LBL) at the University of California, Berkeley, responds here to the assessment of LBL carried by Nature (August 12, page 528)

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

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

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.

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.

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.

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.

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.

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.

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.

Results from the phase ELAD 2 trial reveal that liraglutide is safe and well tolerated in people with mild to moderate Alzheimer’s disease but does not significantly slow brain metabolism decline.

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.

Better understanding the synergy between radiation and corrosion is necessary to deploy advanced nuclear reactors. Here, the authors contradict the misconception that radiation always results in deleterious effects and show that proton irradiation slows the corrosion of Ni-Cr alloys in 650 °C molten salt.

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.