Search

Comprehensive, multinational validation of the PREVENT and SCORE2 cardiovascular risk scores, used in the United States and Europe, respectively, in 44 observational studies and 18 randomized trials, shows similar performance for the two risk scores and generally good performance across geographical regions.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Coastal nitrogen pollution is a critical sustainability challenge with environmental, social and economic consequences. Upstream ‘sweet spots’ where interventions will have maximum mitigation effectiveness and social buy-in are attractive but may prove difficult to implement in urban stream networks.

Endocrine therapies are the main adjuvant therapy for estrogen receptor positive breast cancer, but 30% of patients recur. Here, the authors discover that endocrine therapy upregulates Rac1 signalling component P-Rex1, and inhibition of Rac1 reduces tumour growth in refractory breast cancer models.

Genome-wide analyses identify genetic loci and plasma proteins associated with polycystic ovary syndrome (PCOS). This study highlights the hormonal and metabolic foundations of the disease and explores the impact of polygenic risk for PCOS in both sexes.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

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).

CASP5 expression is restricted to the human intestinal epithelium, and the CASP5C isoform has a key role in promoting Wnt signalling, which is required for epithelial homeostasis, through binding to dishevelled and cleavage of APC to regulate β-catenin turnover.

In a biomarker-driven trial evaluating radiotherapy with erlotinib, everolimus or dasatinib in patients with newly diagnosed diffuse intrinsic pontine glioma, the primary endpoint of overall survival was not met, but features associated with long-term survival were defined, and everolimus emerged as a potential candidate for further testing.

Causal inference should quantify the sensitivity of results to hidden confounders (variables affecting both the location of projects and outcomes). The importance of this is illustrated using analysis of over-crediting in REDD+ projects.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Higher-order interactions are shown to contribute to the decrease in species diversity from low to high latitudes in global forests, potentially explaining why this intricate phenomenon cannot be adequately explained by pairwise interactions alone.

Peritoneal metastasis of ovarian cancer is often accompanied by the accumulation of ascitic fluid. Here, the authors find that ascites protects ovarian cancer cells against ferroptosis, thus enabling their spread in the peritoneum.

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.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

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.

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.

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.

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.

The release of climate-science e-mails last November ripped apart Phil Jones's life. He's now trying to patch it back together.

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

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

It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

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, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

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.

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.

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.

REDD+ projects reduced deforestation, but less than claimed. Synthesising 44 projects, this study finds about 11 times over-crediting due to selection bias in control areas and modelling approaches and concludes that ex post certification is needed.

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.

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.

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.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

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.

Tracking oceanic microbial populations in situ over time is challenging. Here, the authors use autonomous underwater vehicles to show how microbes at the deep chlorophyll maximum respond to diel cycles and isopycnal uplift by a cyclonic eddy.

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.

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.

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.