Search

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

MAGPIE is a computational framework for co-registering spatially-resolved transcriptomics, metabolomics and tissue morphology for integrated downstream analysis. Case studies across lung, brain and breast reveal coordinated cross-modality molecular changes.

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.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Understanding the growth dynamics of GBMs can help expand therapeutic options. Here, authors use a cross-species computational approach to compare GBM cells to healthy neural stem cells, identifying predictors and modulators of tumour growth, including the Wnt antagonist, SFRP1, which stalls growth in preclinical xenograft models.

Niche conservatism is a key assumption when planning non-native species management, but it is not always met. This study suggests that regional differences in niche conservatism are primarily transient and thus a matter of time.

The hypothalamic neuropeptide oxytocin exerts analgesic effects, but the underlying pathways remain largely elusive. Here, the authors describe an analgesic pathway formed by oxytocin neurons projecting to the periaqueductal grey, where axonally released oxytocin activates oxytocin-receptor expressing GABA neurons and subsequently reduces pain-like behaviors in both female and male rats.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The predicted increase in frequency of droughts and rising temperatures in Europe will lead core populations of a temperate plant to an evolutionary dead-end unless they acquire genetic alleles that are present only in extreme edge Mediterranean, Scandinavian, or Siberian populations.

Williams et al. report a growth arrest mechanism in residual cancer persister cells through targeted therapy-induced upregulation of type I interferon signalling, which is negatively regulated by apoptotic DNA endonuclease DFFB to allow tumour relapse.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

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.

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.

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.

Administration of 5-MeO-DMT produces a dissociated brain state in mice, characterized by global slow-wave activity alongside behavioral wakefulness and marked pupil dilation.

T cell immunity declines with thymic atrophy, but thymic cell grafts rescue T cell function.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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).

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.

Using experimental and atomistic simulations, the authors show that optical excitation lowers the energy barrier for domain wall motion. Combined with the imprint field, this effect enables subsecond optical control of domain switching in ferroelectric membranes.

This Perspective considers the addition of ACKR1 genetic testing for identifying ACKR1/DARC-associated neutropenia in patients receiving clozapine, recommending eligibility criteria and testing strategies while estimating substantial cost savings for the UK healthcare system and enhancing equitable treatment access.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Florfenicol amine hijacks intrinsic resistance in Mycobacterium abscessus, highlighting that antimicrobial resistance mechanisms can be harnessed for antibiotic activation.

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.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

The cytosolic innate immune sensor NLRP10 interacts with NLRP3 and mediates the cleavage of oxidized mitochondrial DNA

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

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.

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.

By mapping oxidatively damaged bases and abasic sites at single-nucleotide resolution in human cells, Takhaveev et al. observed transcription-related strand biases, patterns mirroring cancer mutational signatures, and captured the action of the anticancer drug irofulven.

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.

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.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

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.

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.

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.

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.

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.

Li-Fraumeni syndrome leads to an increased predisposition to tumour development. Here, the authors develop a support vector machine model to predict early cancer risk in individuals using peripheral blood DNA methylation profiles.

Proton transfer plays a key role in nature, yet its ultrafast dynamics remain elusive. Here the authors use coincidence spectroscopy and theoretical simulations to show that radiolytic doubly-ionized pyrrole triggers proton transfer to water within 60 fs.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.