Search

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 authors investigated metabolic remodeling in response to stem cell activation and the effect of aging on this response. Aging muscle stem cells lose a key glutamine-fueled metabolic pathway that powers de novo lipogenesis needed for activation. This study shows that reductive TCA cycling helps preserve stem cell function and may offer a new target against sarcopenia.

The epigenetic control of lung development remains insufficiently understood. Here, the authors report a critical role for the chromatin remodeling canonical BAF complex in directing embryonic respiratory development.

CD4⁺ T cells play critical roles in the immune response to intracellular bacterial infection. Here the authors suggest that CD4⁺ T cells can protect in a murine model of Salmonella infection but that the protection occurs in females and is oestrogen dependent.

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).

Natural silk, mechanically strong and biodegradable, offers great potential for sustainable functional materials. Here the authors present a simple thermomechanical method for fabricating high-performance structural and optically active materials directly from silk fibres.

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.

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.

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.

Ribosomal Protein S15 (RPS15) is recurrently mutated in B-cell leukemia but its leukemogenic role remains unclear. Here, the authors establish mutant RPS15 as a cancer driver and reveal mechanisms by which these mutations induce translational defects, DNA damage and genomic instability that together promote leukemogenesis.

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.

Many long noncoding RNA–DNA binding peaks detected using common assays arise from technical artifacts.

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.

Naphthalene rings are common in drug candidates but suffer from metabolic liabilities and limited three-dimensionality. Aryl-fused bicyclo[3.1.1]heptanes (BCHeps) have been presented as derivatizable bioisosteres of β-naphthalene. Now it has been shown that aryl-fused BCHeps can be synthesized and validated as viable naphthyl replacements with promising structural and drug-like properties.

The genomewide meta-analysis of lumbar spinal stenosis LSS identifies 73 previously unreported loci in addition to 15 known loci and highlights spinal degeneration as a key pathogenic mechanism. Overall, the findings expand knowledge of the genetic background of LSS.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

TDP-43 pathology is a key event in ALS/FTD and selectively affects specific neurons in the motor cortex. Here, the authors report which neuron types are affected and demonstrate that transcriptomic changes are cell-type specific.

Snyder et al. analyze two population-based birth cohorts to test associations of newborn metabolite concentrations and childhood respiratory outcomes. C4, C10:1, C18:2, and citrulline are associated with early-life wheezing and asthma, with C18:2 specifically associated with increased non-allergic asthma risk.

As presented at the 2026 AACR Annual Meeting, in a phase 2 trial, treatment of patients with high-risk smoldering multiple myeloma with BCMA-targeting CAR T cell therapy ciltacabtagene autoleucel was safe and led to encouraging rates of clinical responses.

Kancharla, Kelly et al. identify an acridone antimalarial potent across all major parasite life stages. Lead candidate T111 shows oral efficacy, low toxicity, and synergy with tafenoquine, providing a unique mechanism to overcome resistance.

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.

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.

Analyses of epidemiological, clinical and molecular data from a prospective cohort of 3,100 patients with esophageal carcinoma suggest intestinal metaplasia as a single precancer pathway preceding the disease.

Multi-ancestry GWAS meta-analysis identifies risk loci for severe nausea and vomiting of pregnancy. Downstream analyses explore maternal and fetal contributions of these loci and their temporal effects.

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

Alterations of therapeutic pressures have been shown to affect clonal evolution of resistance. Here, the authors conducted a single arm, phase 2 trial consisting of alternating osimertinib and gefitinib in non-small cell lung cancer, and found ctDNA dynamics were predictive of response.

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 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.

Genome-wide analysis coupled with long-read sequencing identifies a repeat expansion in GOLGA8A associated with high risk for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.