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Malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division.

Measuring acoustic oscillations in 27 stars within the M67 cluster presents evidence of a rapidly evolving convective zone as stars evolve from subgiants to red giants.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Whole-genome sequencing of tumour and germline DNA samples from 92 patients with high-grade serous ovarian cancer identifies frequent gene breakages that inactivate the tumour suppressors RB1, NF1, RAD51B and PTEN, and contribute to chemotherapy resistance; acquired resistance was associated with diverse mechanisms such as reversions of germline BRCA1/2 mutations and overexpression of the drug efflux pump MDR1.

Cumulus is a cloud-based framework enabling large-scale single-cell and single-nucleus RNA sequencing data analysis.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

The authors discovered cluster of regulatory sequences that controls HOXA over large genomic distances and across topological domains. This cluster is required for normal craniofacial development in both humans and mice.

A general reinforcement-learning algorithm, called Dreamer, outperforms specialized expert algorithms across diverse tasks by learning a model of the environment and improving its behaviour by imagining future scenarios.

Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.

Assessment of metagenomic sequencing of cell-free DNA directly from patient samples as a diagnostic for infections.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Food allergy is a growing clinical and public health burden. Here, the authors carry out a genome-wide association study in samples with well-defined allergies to a variety of foods, and identify the 6p21.32 region that significantly increases risk of developing peanut allergy.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Paul Boutros, Robert Bristow and colleagues report a molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer. They find that multifocal tumors are highly heterogeneous, and they identify a novel recurrent amplification of MYCL1.

Functional diversity and phylogenetic diversity are expected to be positively correlated. Here the authors show that the covariation between these metrics in vascular plant communities around the world is often either inconsistent or negative.

Chronic lymphocytic leukaemia has a hereditary component, much of which remains to be identified. Here, the authors perform a genome-wide association study and find new risk loci for the disease, which are associated with genes involved in immune function.

Using genetically engineered models, Genovese and colleagues study patterns of convergent evolution in renal cancer, and pinpoint dysregulation of interferon signaling as a means of adaptation to chromosomal instability in metastatic progression.

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is important for early detection and treatment. Here, the authors use a multigene next-generation sequencing panel to identify genomic differences in Nigerian CRCs compared to those from TCGA and MSKCC cohorts.

In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.

RNA sequencing (RNA-seq) is increasingly being integrated into molecular tumour profiling but remains underutilized for clinical decision-making. This Perspective presents a framework for assessing the therapeutic, diagnostic and prognostic actionability of RNA-seq findings as well as an ‘actionable transcriptome’ list to help guide the application of RNA-seq findings in oncology practice.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Here the non-linear relationship is revealed between carbon emissions reductions and oil demand reductions, which depends on the magnitude of demand drop and the global oil market structure.

The authors present the largest genome-wide association study to date for a rare Parkinsonian disorder, progressive supranuclear palsy (PSP). They include follow-up investigations of the identified susceptibility loci, functional consequences, and cell-specific pathologies, providing insights into genetic and molecular mechanisms underlying PSP.

There is a need for methods that allow the analysis of single-cell long-read sequencing data without depending on known barcode lists or short-read sequencing. Here, the authors develop scNanoGPS, a tool that can independently deconvolute long reads into single cells and single molecules, and apply it on tumour and cell line data.

Tim Chan and colleagues report the identification of recurrent somatic mutations in FAT1 in glioblastoma, colon cancer and head and neck cancer and show that inactivation of FAT1 promotes Wnt signaling and tumorigenesis.

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.

This array with 623,124 SNP probes and 916,269 probes to query structural variants opens the door to a detailed characterization of genetic diversity in laboratory mouse strains. This will allow genome-wide association studies in mice.

The decades-old limit on how long human embryos can be grown in culture is under debate. A new road map outlines how to extend the length of culture responsibly.

The evolutionary history of pigs in Africa is unclear. Here, the authors examine 67 whole genomes, finding incomplete speciation between bushpigs and red river hogs as well as evidence suggesting that humans brought bushpigs to Madagascar 1000-5000 years ago.

Addressing nutrition and climate resilience together requires transdisciplinary participatory action research with clear impact pathways for systems change that starts from the ground up. The concept of ‘crops that nourish’ is proposed here to offer a new mode of pursuing agricultural development. It involves iterative co-creation between farmers and researchers that prioritizes local needs and agency, human health, resilience and sustainability through a focus on opportunity crops.

It is challenging to analyse chromosomal rearrangements in heterogeneous solid cancers. Here the authors present HiDENSEC, a method to jointly infer absolute copy number, ploidy, tumor purity and large-scale rearrangements from Hi-C data. The increased statistical power afforded by joint inference enables novel insights into cancer genome evolution.

Using lidar over an area of 85,000 km², Inomata et al. identified 478 early ceremonial complexes in southern Mexico. These discoveries offer new information for understanding the origins of Mayan civilization and its relation with the Olmecs.

Genome-wide association analyses of two oral glucose tolerance test-derived measures of postprandial insulin resistance discover ten new loci. Functional characterization identifies nine candidate genes implicated in the regulation of GLUT4.

Humans can infer rules for building words in a new language from a handful of examples, and linguists also can infer language patterns across related languages. Here, the authors provide an algorithm which models these grammatical abilities by synthesizing human-understandable programs for building words.

Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.

The clinical course of chronic lymphocytic leukaemia (CLL) is variable and difficult to predict. Here, the authors conduct a genome wide association study meta-analysis for time to first treatment in CLL patients and report two loci associating with progressive disease.

Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.

Evaluation of the efficiency of land-use changes and their effect on global carbon storage shows that several land-use and consumption choices relevant to climate policy have greater implications than previously thought.

Rinse Weersma, Carl Anderson and colleagues report the results of a trans-ancestry association study of inflammatory bowel disease. They implicate 38 new susceptibility loci, and show that the variance explained by each IBD risk locus is consistent across diverse ancestries, with a few notable exceptions.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Cyclic peptides are of particular interest due to their pharmacological properties, but their design for binding to a target protein is challenging. Here, the authors present a computational “anchor extension” methodology for de novo design of cyclic peptides that bind to the target protein with high affinity, and validate the approach by developing cyclic peptides that inhibit histone deacetylases 2 and 6.

A torque magnetometry study of the pyrochlore iridate Eu₂Ir₂O₇ reveals an unusual symmetry-breaking effect that persists above the Néel temperature of this antiferromagnet.

Genomic profiling of tumours can help tailer treatments to the patient, however, it often fails to accurately predict therapeutic outcomes. Here, the authors combine molecular and functional characterisation via BH3 profiling to identify therapeutically targetable vulnerabilities in glioma.

Federated learning can be used to train medical AI models on sensitive personal data while preserving important privacy properties; however, the sensitive nature of the data makes it difficult to evaluate approaches reproducibly on real data. The MedPerf project presented by Karargyris et al. provides the tools and infrastructure to distribute models to healthcare facilities, such that they can be trained and evaluated in realistic settings.

The Tyrolean Iceman is 5,300 years old and his mitochondrial genome has been previously sequenced. This study reports the full genome sequence of the Iceman and reveals that he probably had brown eyes, was at risk for coronary disease and may have been infected with the pathogen Lyme borreliosis.