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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.

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.

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.

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.

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

Warming temperatures and interactions between plants are the main drivers of changes in Arctic plant communities in response to climate change, and there is no evidence of overall biotic homogenization.

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.

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.

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.

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.

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.

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

Intracytoplasmic sperm injection, usually reserved for cases of male infertility, was found to be nonsuperior to conventional in vitro fertilization in couples without male infertility concerns.

Integrated data, including 100 human genomes from the Mesolithic, Neolithic and Early Bronze Age periods show that two major population turnovers occurred over just 1,000 years in Neolithic Denmark, resulting in dramatic changes in the genes, diet and physical appearance of the local people, as well as the landscape in which they lived.

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.

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.

Dietary protein restriction in healthy, lean men elicits an increased energy intake to maintain body weight, which is driven, at least in part, by FGF21-mediated alterations to adipose tissue mitochondria.

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.

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.

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.

Sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation. Here we show that among patients with atrial fibrillation, the excess stroke risk for female patients vs male patients has been declining, with risk-score adjusted relative risk estimates suggesting limited difference in most recent years.

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.

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 combination of animal studies, data from a clinical trial and insights from an observational cohort suggest that, in individuals with metabolic dysfunction-associated steatohepatitis, semaglutide improves liver histology by reverting patient proteomes to better mimic the proteome of individuals without the disease.

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.

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.

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 the era of global foodborne pathogens’ genomic surveillance, this study shows that large-scale inter-laboratory comparisons are needed and feasible, opening good perspectives for efficient and cooperative One Health outbreak investigations.

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.

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.

The dopamine transporter, DAT, controls dopamine signaling by facilitating its reuptake using the Na⁺ gradient as driving force. Here, the authors uncover that an antiport of K⁺ ions also contributes to setting the rate of DAT-mediated dopamine clearance.

Effective treatments for myelin repair are currently lacking. Here, the authors show that two FDA-approved drugs, leucovorin and dyclonine, identified through pharmacogenomic screening, promote oligodendrocyte formation and brain repair in myelin injury models.

Electroreduction of CO₂ to CO is a potential valorisation pathway of carbon dioxide for fine chemicals production. Here, the authors show a user-friendly device that couples CO₂ electroreduction with carbonylation chemistry for up to gram scale synthesis of pharmaceuticals even under atmospheric CO₂.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

The authors report findings from the MOBILIZE trial, which found that exercise therapy and self-management support improved patient-reported quality of life in individuals with multiple chronic conditions.

Molecular solar thermal systems are promising for storing solar energy but achieving high energy storage densities and absorption characteristics matching the solar spectrum is challenging. Here the authors present a design strategy for electronically coupled photoswitches which allow for high energy density storage for solar energy storage applications.

The realization of the fractional quantum Hall effect with ultracold atoms in optical lattices is much sought after. Here, the authors propose a new way of obtaining fractional quantum Hall states in lattice systems by transforming a nonlocal abstract model into an implementable scheme.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

A randomized controlled trial found no difference in paranoid ideations between virtual reality-based and gold-standard cognitive behavioral therapy for patients with schizophrenia spectrum disorders, in contrast to previous trials using wait-list or passive controls.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.