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Trans-ancestry genome-wide analyses identify multiple loci associated with ascending aortic diameter. A polygenic score constructed from these loci predicted prevalent risk of thoracic aortic aneurysm in independent populations.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

MYC is an iconic oncogene that has been at the forefront of cancer research since its discovery. Looking back over the history of MYC research provides us with a framework with which to progress in the next 25 years, as outlined in this Timeline.

Hundreds of RNAs and proteins are imaged in fixed tissue at subcellular resolution.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.

The size of non-fluorescent nanodiamonds can be tracked in cells through coherent anti-Stokes Raman scattering, which could be used for following cellular pathways quantitatively.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

The innate sensors of SARS-CoV-2 are still being determined. Kanneganti and colleagues find that SARS-CoV-2 envelope protein is sensed by TLR2 and this drives pathogenic inflammatory cytokine production.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to ~6% of both male and female cases and therefore does not solely explain male bias in DDs.

Ultrasound neuromodulation overcomes limitations of electrode-based stimulation through improved

targeting and long-term stability for treating neurological disorders. Here, authors present a hair-thin, implantable piezoelectric stimulator that selectively modulates neurons in the deep brain.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Ion-selective membranes are widely used for water purification and electrochemical energy devices but designing their pore architectures is challenging. Membranes with narrow channels and hydrophilic functionality are shown to exhibit salt ions transport and selectivity towards small organic molecules.

Pathogenic autoreactive antibodies associated with severe COVID-19 can be identified via self-assembled genome-scale libraries of full-length proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca²⁺ transport and AMPAR currents.”

Genome sequencing and phylogenomic analysis show that the lungfish, not the coelacanth, is the closest living relative of tetrapods, that coelacanth protein-coding genes are more slowly evolving than those of tetrapods and lungfish, and that the genes and regulatory elements that underwent changes during the vertebrate transition to land reflect adaptation to a new environment.

Long-term cultures of human brain organoids display a high degree of cellular diversity, mature spontaneous neuronal networks and are sensitive to light.

Circulating liver enzymes, like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are highly heritable and predictive of disease. Here, the authors perform a genome-wide association study on ALT and AST, revealing a rare variant in SLC30A10 associated with elevated ALT and AST.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

Trisomy 21 (T21) is a major cause of Down syndrome but little is known about its impact on the cellular proteome. Here, the authors define the proteome of T21 fibroblasts and its turnover and also map proteomic differences in monozygotic T21-discordant twins, revealing extensive, organelle-specific changes caused by T21.

The anthrax lethal toxin protein transporter consists of protective antigen (PA) and lethal factor (LF), with LF unfolding for translocation into the host cell. Structural and functional analyses now indicate how each of four LFs unfolds and binds into amphipathic clefts on the surface of the PA octomer.

The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.

Fuchs and colleagues report a role for the F-actin binding protein Wdr1 in the establishment of planar polarity in the mouse embryonic epidermis by mediating tension.

The naturally occurring compound urolithin A has been found to promote mitophagy, thereby increasing lifespan in worms and improving skeletal muscle activity in rodents.

Here, the first genome-wide in vivo RNA interference screens in a mammalian animal model are reported: genes involved in normal and abnormal epithelial cell growth are studied in developing skin tissue in mouse embryos, and among the findings, β-catenin is shown to act as an antagonist to normal epithelial cell growth as well as promoting oncogene-driven growth.

The authors use modelling to show that the network of trading routes known as the Silk Road emerged from hundreds of years of interactions between pastoralists as they moved their herds and flocks between higher and lower elevations in generally mountainous regions.

Kim Worley and colleagues report the whole-genome sequence of the common marmoset, Callithrix jacchus, the first New World monkey to be sequenced.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Planar cell polarity (PCP) directs the orientation of mammalian epithelial cells in the skin but it is unclear how polarity is preserved during division. A dileucine motif in the atypical cadherin Celsr1 is shown to trigger the endocytosis of PCP components in mitosis to ensure that they are distributed equally to daughter cells and recycled back to the plasma membrane after division.

Systems-wide analysis of HeLa cell lines from 13 labs identifies substantial molecular and phenotypic variability.

Despite large numbers of patients being affected by stones, a surprising lack of knowledge exists on the relevance of stone compositions and pathological features to the outcomes of patients with stones. Here authors describe the potential of new technologies such as high-resolution endoscopes, and micro-CT imaging to address this lack of knowledge.

Rapid assessment of xenobiotic molecules is crucial due to their potential health risks. Here, the authors employ drift tube ion mobility spectrometry-mass spectrometry (IMS-MS) to analyse 2144 xenobiotic standards, creating a comprehensive database that enhances screening capabilities and accelerates exposure response.

Ruthenium oxide has attracted recent interest as a non-superconducting material where superconductivity can be induced by epitaxial strain. Here, the authors explore strained (100)-oriented RuO₂ films on TiO₂(100) substrate and reveal strain-induced superconductivity similarly to strained RuO₂(110) films, providing insights into the thickness-dependence and electronic structure mechanisms of superconductivity.

Analytes can be ionized and brought into the gas phase using electrospray ionization (ESI). Coupling ESI with mass spectrometry enables a wide range of molecules to be studied, including proteins and polymers. This Primer introduces the ESI method, describing the underlying mechanism, common variants and instrument setups.

The Paris Agreement highlights the need for local climate leadership. The University Of California’s approach to deep decarbonization offers lessons in efficiency, alternative fuels and electrification. Bending the emissions curve globally requires efforts that blend academic insights with practical solutions.