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Soil microbes drive ecosystem functions but are vulnerable to environmental stressors triggered by global change. This study reveals that multiple environmental stressors drive community-level restructuring of soil functional microbiomes globally.

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

The study identifies novel genetic variants linked to core cerebrospinal fluid Alzheimer’s Disease biomarkers using a genome-wide analysis, showing how endophenotypes can identify genes and disease mechanisms not captured by case-control studies.

Genome-wide analysis shows European dogs existed by 14,200 years ago, were already genetically distinct, received less Neolithic Southwest Asian admixture than humans did and contributed substantially to later European dogs.

Analysis of eukaryotic gene sequences using a relaxed molecular clock methodology indicate that eukaryotes emerged 3.0–2.25 billion years ago as a result of mitochondrial endosymbiosis with complex archaea that already possessed an elaborated cytoskeleton, membrane trafficking, endomembrane, phagocytotic machinery and a nucleus.

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.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

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.

Analysis of the eukaryotic gene repertoires mediating central carbon metabolism identifies ancestral contributions from Alphaproteobacteria, Asgardarchaeota and other microbial taxa, followed by gene loss, transfer and subcellular retargeting, which have remodelled central carbon metabolism over time.

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 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.

The permeability of bacterial porins is dynamically regulated by periplasmic proton and potassium concentrations, altering antibiotic resistance.

A potential drug should specifically interact with its intended target in order to limit unwanted side effects. Here, the authors fabricate a biodegradable polymer nanoparticle with a fluorescent hepatic uptake transporter ligand to achieve targeted in vivosiRNA delivery and imaging of delivery.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

The timing of cellular evolution is poorly constrained. Here, the authors used improved molecular dating approaches to study the evolution of the ATP synthase in light of a dated tree of life thereby providing an absolute timescale for cellular evolution including eukaryotic origins.

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

While coffee and tea consumption has been associated with risk of diseases, their mechanisms of action remain elusive. Here the authors present a large EWAS on coffee and tea consumption in cohorts of European and African-American ancestries, finding that coffee consumption is associated with differential DNA methylation levels at multiple CpGs.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

In patients who require revascularization after myocardial infarction, noninvasive imaging tests can be useful to assess whether target areas of the myocardium are viable. Delayed-enhancement MRI allows direct visualization of potentially damaged regions, but it is still a new technique. This review explores its role in the routine evaluation of coronary artery disease patients.

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.

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.

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.

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.

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.

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.

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.

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.

Integration of phylogenetics, comparative genomics and palaeobiological approaches suggests that the last universal common ancestor lived about 4.2 billion years ago and was a complex prokaryote-grade anaerobic acetogen that was part of an ecosystem.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Integrin proteins regulate important cellular processes such as proliferation and differentiation. Here the authors show that siRNA-mediated knockdown of two integrin subunits slows down progression of hepatocellular carcinoma in mice by reducing activation of the METoncogene.

The influence of chromatin structure on the DNA replication programme is reciprocated by replication-coupled mechanisms that re-establish chromatin on newly formed DNA. The tight coupling of these processes is essential for promoting integrity of the genome and epigenome, with possible implications for ageing and cancer.

The TAK1 kinase binds K63-linked ubiquitin specifically via its TAB2 subunit. The structure of the TAB2 NZF domain in complex with K63-linked ubiquitins now indicates that this domain interacts with neighboring ubiquitins through distinct sites, explaining the basis of specific recognition.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

The evolutionary relationships within Archaea remain unresolved. Here, the authors used genomic approaches to study the Undinarchaeota, a previously uncharacterized clade of DPANN, shed light on their position in an updated archaeal phylogeny and illuminate the history of archaeal genome evolution.

Protein abundance is controlled at the transcriptional, translational and posttranslational levels. Here, Öztürk et al. determine proteome changes resulting from individual knockout of 3308 nonessential genes in the yeast S. pombe, infer gene functionality, and show that protein upregulation under stable transcript expression utilizes optimal codons.