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Results from integrative population-based investigations indicate co-occurring types of clonal hematopoiesis are highly enriched and markedly increase blood cancer risk, highlighting new opportunities for early detection and targeted surveillance of high-risk individuals.

Here, the authors provide a framework to map glucuronidated metabolites and show that gut microbes shape their distribution across the body, with findings in mice supported by human data, where colonization and diet influence glucuronidation patterns.

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.

Selecting appropriate treatment for breast cancer is guided by molecular subtypes and clinical characteristics. Here, the authors show that their AI-based approach, which integrates digital pathology images and clinical data, demonstrates robust accuracy in predicting the risk of cancer recurrence across major molecular breast cancer subtypes, including triple negative breast cancer.

This study reveals that the divergent Plasmodium NEK4 kinase acts as a central regulator of early post-zygotic meiosis. It couples crucial cytoskeletal reorganisation, such as MTOC duplication and nuclear migration, with chromosomal dynamics to drive meiotic entry and parasite development.

Curiosity detected over 20 organic molecules in 3.5-billion-year-old Martian rocks using a wet chemistry experiment, showing complex carbon compounds can survive for billions of years and may preserve clues about Mars’ past habitability

Davidovich et al. investigate allele-specific DNA methylation inheritance patterns in mouse liver and muscle. Most patterns are Mendelian, but ~7% are non-Mendelian, including new imprinted genes and a paramutation at the Capn11 locus.

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.

In this phase 2 trial, Perez et al. reported the safety of the vitamin D receptor agonist paricalcitol with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma and the pharmacodynamic effects of paricalcitol in fibroblasts and immune cells.

Cryo-EM analysis of amyloid fibrils from patients with hereditary ApoA-I amyloidosis shows that different disease mutations can produce distinct fibril structures depending on their position relative to the fibril core, which may influence organ damage and clinical outcomes.

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.

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.

This study develops a platform that enables simultaneous, multiplexed tracing of 30 nitrogen isotope-labelled metabolites, uncovering differences in pyrimidine synthesis pathway choice between primitive and differentiated cells.

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.

Using cryo-EM, this study reveals the structures of amyloid fibrils from a patient with ALECT2 amyloidosis, uncovering structural polymorphism of full-length ALECT2 fibrils and identifying features that may inform future diagnostics and treatments.

A range of humoral related adverse events can occur after treatment of haematological malignancy with chimeric antigen receptor cell therapies. Here the authors characterise the persistence of humoral immunity and response to vaccination after patients receive B cell targeted chimeric antigen receptor T cell therapy.

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.

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.

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.

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.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

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.

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.

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.

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).

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.

A vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display generates cross-neutralizing HIV serum antibody responses in non-human primates, mimicking infection-elicited apex-targeting broadly neutralizing antibodies.

Otopetrins form proton channels in animals ranging from nematodes to humans. Here, authors identify small molecule inhibitors and characterize their binding in the intrasubunit interface region, thus highlighting the area for pharmacological targeting for channel modulation.

Rapid methods to identify antigen-specific T cells are essential for developing targeted immunotherapies. Here the authors present a high-throughput MHC class II single-chain trimer platform for the comprehensive profiling of CD4⁺ T cells, enabling the rapid identification and characterization of virus- and tumour-specific T cell receptors (TCR) at single-cell resolution.

Compared to the oxygenation of Earth’s atmosphere, little is known about the build up of dissolved oxygen in the oceans. Vanadium isotopes in shales suggest shallow oceans equilibrated with a newly oxygenated atmosphere in just a few million years.

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 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.

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

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.

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.

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.

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.

Protection against Mycobacterium tuberculosis infection among heavily exposed tuberculosis household contacts in Indonesia correlated with circulating metabolite levels and genotypes, and with ex-vivo mycobacterial growth in healthy Dutch controls.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The rapid evolution of SARS-CoV-2 challenges antibody therapeutics, but glycan-masked antigens enable isolation of class 3 monoclonal antibodies that potently neutralize diverse Omicron variants and reveal cross-reactive epitopes.

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.

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.

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.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

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.