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Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Salladay-Perez and colleagues explore senescence induction in human and mouse macrophages using multiomic profiling. They characterize a p21⁺TREM2⁺ senescent macrophage population, which they functionally implicate in inflammaging and liver disease.

The mechanisms driving reversible dedifferentiation events towards a drug-tolerant persister (DTP) state remain to be explored. Here, multi-omics, information-theoretic approaches and dynamic systems modelling highlight the role of the oxidative-stress–mediated NF-κB/RelA axis in driving the transition towards DTP across multiple cancer types.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Here, the authors leverage stable isotope and peptide analyses to show that some 18th century Māori individuals ate largely plant-based diets. This work aligns with Māori oral history and archaeological evidence, which points to sweet potato and taro cultivation as important for population growth and cultural change at the time.

LIGO–Virgo–KAGRA’s fourth Gravitational-Wave Transient Catalog shows evidence of a clear pair-instability gap in the distribution of binary black-hole secondary masses but is absent in the larger primary masses.

Adalatherium hui, a newly discovered gondwanatherian mammal from Madagascar dated to near the end of the Cretaceous period, shows features consistent with a long evolutionary trajectory of isolation in an insular environment.

In a phase 1b trial, patients with treatment-naive metastatic pancreatic adenocarcinoma received the CD73 inhibitor quemliclustat plus gemcitabine and nabpaclitaxel with or without the anti-PD1 antibody zimberelimab, showing encouraging clinical response rates and survival in quemliclustat-treated patients.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

A computer Go program based on deep neural networks defeats a human professional player to achieve one of the grand challenges of artificial intelligence.

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

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

The vacuum process is scalable and solvent free, yet all-vacuum-deposited perovskite solar cells still trail solution-processed counterparts. Facet-directed co-evaporation yields (100)-oriented mixed-halide wide-bandgap films for efficient, stable single-junction cells and perovskite–silicon tandem cells.

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.

The herpes simplex virus lytic-latent balance is incompletely understood. In this study, the authors show that it is controlled by the relative abundance of host activating and repressive forkhead box (FOX) transcription factors that recruit epigenetic cofactors to the viral genome to remodel viral chromatin.

This study uses two large fundus cohorts to show that retinal foundation models generalize well across populations but exhibit age-related fairness gaps. It highlights how pre-training data composition shapes model generalisability and fairness.

Many vascular‑disease risk loci lack defined causal genes. Here, the authors integrate functional genomics and CRISPR screens to identify genes influencing smooth muscle cell behaviour, validating roles for FES, BCAR1, CARF and SMARCA4, with Fes loss promoting atherosclerosis and hypertension.

Starting from zero knowledge and without human data, AlphaGo Zero was able to teach itself to play Go and to develop novel strategies that provide new insights into the oldest of games.

Inflammatory bowel disease (IBD) is highly prevalent among the Ashkenazi Jewish population. Here, the authors identify novel IBD-associated variants and genes, validated by transcriptomic and phenome-wide associations.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In correlated materials, new phases emerge when the balance between many-body interactions is perturbed. Here, Ma et al. induce a mosaic charge-density-wave phase out of Mott insulating state in layered 1T-TaS₂by voltage pulses, which reveals a dominating role of interlayer stacking order.

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.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

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.

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.

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.

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.

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.

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.

Vaccine-derived poliovirus type 2 currently spreads similarly to historical poliovirus—unidirectionally across neighbouring countries at a median velocity of 2.3 km per day. International borders are associated with slower velocity when immunity is high.