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The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

In this randomized phase 3 trial, patients with treatment-naive stage III–IV nonsmall cell lung cancer who received sintilimab or pembrolizumab in combination with chemotherapy early in the day (before 15:00 h) experienced longer progression-free survival compared with those receiving late time-of-day infusions.

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

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

Genetic predictors of health outcomes often drop in accuracy when applied to people dissimilar to participants of large genetic studies. Here, the authors investigate the root causes and highlight open questions underlying this problem.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Here they show that the E3 ubiquitin ligase CTLH supports mTORC1. Upon CTLH inactivation, ZMYND19 and MKLN19 accumulate, associate, and block mTORC1/RHEB association. CTLH and PI3K inhibition are synthetic lethal for EBV-associated gastric cancer.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Ecosystems accumulate carbon for several days after moisture pulses, but this benefit fades as soil dries and heat stress intensifies, according to an analysis that uses carbon flux-tower observations, Earth system models, machine learning, and satellite images.

Electron distributions exhibit velocity-space signatures indicative of the rapid energy released by magnetic reconnection explosions occurring in Earth’s magnetosphere and in plasmas throughout the universe. Here, the authors discover a smile-shaped signature in the electron gradient distribution associated with reconnection occurring at Earth’s dayside magnetopause boundary.

Extrachromosomal DNA (ecDNA) drives oncogene amplification, tumour evolution and therapy resistance across cancers. This Review summarizes advances in ecDNA biology, highlights emerging therapeutic vulnerabilities and outlines strategies to improve ecDNA detection and translate ecDNA-targeted approaches from bench to bedside.

Extrachromosomal circular DNAs (ecDNAs) are prevalent in human cancers and are thought to drive tumor evolution and drug resistance by amplifying oncogenes. Here, authors develop ec3D to reconstruct three-dimensional ecDNA structures, revealing how their spatial organization rewires regulatory circuits.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

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.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

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.

Here the authors report an allotrope to the nanocarbon family, Graphene-P-phenyl-Graphene, for potassium-ion batteries.

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.

Particle fusion is a promising process for constructing nanomaterials, but challenging to control in synthetic systems. Here, the authors report a method for kinetically regulated particle fusion controlled by variation in polymer chain length.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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 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 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.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

A combination of genome-wide functional screening, imaging and chromatin profiling identifies a new class of highly prevalent genomic elements that help retain extrachromosomal DNA copies in dividing cells and persist across generations.

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.

Electrochemical CO₂ reduction to formate offers a sustainable route but has been difficult to achieve selectively on transition metals. Here, the authors show that chalcogenide-stabilized Cu⁺, via charge redistribution, enables near-complete formate production with industrially relevant efficiency.

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.

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.

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 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.

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 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 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.