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This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

As presented at the 2025 ASCO GI Cancers Symposium: in the phase 3 BREAKWATER trial, patients with previously untreated BRAF V600E metastatic colorectal cancer received the BRAF inhibitor encorafenib, the anti-EGFR monoclonal antibody cetuximab and chemotherapy mFOLFOX6 versus investigator’s choice of chemotherapy with or without bevacizumab, leading to an improved objective response rate, with the dual primary endpoint of progression free survival still maturing.

The combination of a bispecific antibody against EGFR and MET with a tyrosine kinase inhibitor (TKI) in patients with TKI-relapsed, chemotherapy-naive, EGFR-mutated advanced NSCLC is safe and shows preliminary efficacy.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

One of two papers demonstrating that there is a common progenitor for cortical and medullary tissue types in the thymus — when epithelial precursor cells are marked and then injected back into a developing thymus, both cortical and medullary tissues are derived from the marked precursor cells.

In mice, prolonged consumption of a high-fat diet decreases interest in calorie-rich foods as a result of reduced neurotensin expression and signalling, which uncouples hedonic feeding behaviour linked to neurons projecting from lateral nucleus accumbens to ventral tegmental area.

The nuclear envelope tethers chromatin to the nuclear periphery to control genome architecture. Here, the authors show that Net39 preserves the integrity and gene expression of muscle nuclei in mice, and it may contribute to the pathogenesis of Emery–Dreifuss muscular dystrophy.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

In this study, the authors use electronic health record data from the US to characterise post-acute sequelae of SARS-CoV-2 infection (PASC). They identify 17 common PASC conditions and find an overall ~12% increase in risk of PASC conditions in the post-acute period among people with a SARS-CoV-2 positive test compared to matched test-negative controls.

Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Using whole-genome sequencing data from 1,739 individuals, the GenomeAsia 100K Project catalogues genetic variation, population structure and disease associations to facilitate genetic studies in Asian populations and increase representation in genetics studies worldwide.

Fasting induces hepatic autophagy to preserve energy homeostasis. Here the authors report that fasting induced fibroblast growth factor 21 signalling induces autophagy by activating lysine-specific demethylase 6B, leading to histone demethylation mediated activation of autophagy genes.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

The FLIGHT-FXR trial, testing farnesoid X receptor agonist tropifexor in nonalcoholic steatohepatitis, demonstrated sustained decreases in alanine aminotransferase levels and hepatic fat fraction, but not aspartate aminotransferase, with dose-dependent pruritus being the most common adverse event.

We present James Webb Space Telescope observations that detect the 3.3 μm polycyclic aromatic hydrocarbon feature in a galaxy observed less than 1.5 billion years after the Big Bang.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Analysis of two-million-year-old ancient environmental DNA from the Kap København Formation in North Greenland shows there was an open boreal forest with diverse plant and animal species, of which several taxa have not previously been detected at the site, representing an ecosystem that has no present-day analogue.

Using proteomic analyses, Eric Rubin, Véronique Dartois and colleagues show that tuberculosis granulomas have spatially segregated protein compositions that compartmentalize pro- and anti-inflammatory responses to distinct regions.

Single-molecule-based sequencing technology is applied to generate genome-wide maps of chromatin modifications in mammalian cells. Histone marks can discriminate genes that are active, poised for activation, or stably repressed and therefore reflect cell state and developmental potential.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

During wound induced hair follicle neogenesis (WIHN), stem cells regenerate hair follicles but how this arises is unclear. Here, the authors show that self-noncoding dsRNA activates the antiviral receptor TLR3 to induce intrinsic retinoic acid, which stimulates WIHN in mice, and in isolated human keratinocyte cells.

GATA-binding protein 4 (GATA4) is reported to control cell proliferation in cancers. Here the authors show that GATA4’s pro-inflammatory secretome promotes the recruitment of immune cells such as CD8 + T cells to suppress tumour initiation and growth in a non-cell autonomous manner.

A large array of ferroelectric field-effect transistors with record memory windows, ON/OFF ratios and ON-current density is presented at ~80 nm channel length.

A non-volatile memory device that is based on an aluminium scandium nitride (Al_0.68Sc_0.32N) ferroelectric diode can operate at temperatures of up to 600 °C.

Based on computations, the authors show that voltage stability of battery electrolytes is determined not by a single component but by formation of charge transfer complexes between salt anions and solvent molecules. A physical model is proposed and validated on several common electrolyte compositions.

A population of neutrophils in the skin produces extracellular matrix, providing a defence strategy by reinforcing the barrier properties of the skin and helping to block the entry of pathogens.

Characteristics of spin waves in recently discovered two-dimensional (2D) Ising ferromagnets are still lacking. Here, Jin and Kim et al. report Raman resonance evidence of two sets of surface spin waves in the 2D honeycomb ferromagnet CrI₃.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Insulin receptor protein is present in pancreatic β-cells, but the consequences of β-cell insulin resistance are incompletely understood. Here the authors use a combination of mouse studies and mathematical modelling to show that loss of beta-cell insulin receptor affects male and female mice differently and can contribute to hyperinsulinemia in the context of glucose stimulation.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Recent barcoding technologies allow the reconstruction of a cell’s lineage tree while capturing paired transcriptomic data. Here, the authors present a statistical method to automatically detect gene expression patterns related to lineage progression.