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AlphaGenome, a deep learning model that inputs 1-Mb DNA sequence to predict functional genomic tracks at single-base resolution across diverse modalities, outperforms existing models in variant effect prediction and enables comprehensive genomic analysis.

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.

Much investment goes into improving police-community interactions, yet trust in police remains low. Here, the authors show that community members report feeling less threat and more trust when officers use transparency statements to start interactions.

PFAS are “forever chemicals” that build up in living things and can move through food webs. This study shows their levels roughly double with each step up the food chain, highlighting widespread chemical magnification in nature.

The spatial pattern of climate change is uncertain. Analyses of a simple model suggest that uncertainty in tropical feedbacks induces a global response, but the impact of uncertainty in polar feedbacks tends to be limited to the region.

The separation of enantiomers by flows holds promise in food and pharmaceutical industries, but the feasibility remains uncertain. Here, Hermans et al.separate macroscopic particles of opposite chirality at a liquid interface using shear flows, which provides insights into the mechanism at nanoscale.

Magnetohydrodynamic instabilities are related to different characteristics and behavior of fluids. Here the authors report an experiment and simulation combined study of a global non-axisymmetric MHD instability that exists at sufficiently large rotation rates and intermediate magnetic field strengths.

cfDNA fragmentomics is a potential clinically applicable method for identifying cancer. Here, the authors assess fragmentomics analysis methods and their application to commercial targeted sequencing panels.

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.

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.

CAR-T cells have been found to be less effective as treatment for solid tumours. Here the authors, utilising B7H3 as an antigen, consider how changes in B7H3 binders lead to functional changes of CAR-T cells and differences in tumour outcomes in humanised mouse tumour models.

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.

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.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

Air pollution has been linked to neurodegenerative disease. Here the authors carried out a population-based cohort study to investigate the association between long-term exposure to PM_2.5, NO₂, and warm-season O₃ on dementia and Alzheimer’s disease incidence in the United States.

APOBEC3B interacts with R-loops and helps mediate their resolution in a deamination-dependent way. This association also renders R-loops susceptible to enhanced APOBEC3B-dependent mutagenesis.

Using intracerebral recordings, the authors find abstract prosodic categories in continuous speech are encoded differently to segmental features by Heschl’s gyrus, suggesting specialized cortical processing early in the auditory processing hierarchy.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

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.

Forecasts of the feedback between adaptive energy use and climate change show energy-based adaptation will lower global mean surface temperature in 2099 by 0.12 °C, reducing required Paris Agreement mitigation for 85 percent of committed countries.

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

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.

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.

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.

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.

Here, the authors describe the global distribution of crAssphage, its presence in Old-World and New-World primates, and its association with gut bacterial communities and dietary factors, providing insights into the origin, evolution and epidemiology of human gut crAssphage.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

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 demonstrate a 3-tier mass spectrometry approach, including bottom-up and top-down proteomics, as well as native mass spectrometry to provide a detailed description of proteoforms, protein processing and post-translational modifications present within ribosomes from bacteria, plant, and human.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

The authors determine the synaptic wiring diagram of a vertebrate circuit and reveal behaviorally associated modules. A model based on this connectome predicts neural coding and dynamics that are verified with calcium imaging data.

Sudan virus (SUDV) outbreaks in Uganda created public health concerns due to a lack of approved vaccines. In this study, the authors develop a repRNA SUDV vaccine and demonstrate full protection of a single dose of this vaccine in a lethal SUDV guinea pig model.

Glioma tumours are known to be heterogenous in mutation and gene expression patterns, but sampling limitations can lead to inaccurate detection of evolutionary events. Here, the authors carry out multi-omics analysis of multi-regional biopsies from 68 patients and show differential mutations in non-enhancing regions.

Abeysundara, Rasnitsyn, Fong et al. report that the presence of leptomeningeal metastatic tumour cells leads to the recruitment and remodelling of fibroblasts, which, in turn, facilitate the colonization and outgrowth of medulloblastoma cells in the leptomeninges.

The relationships that control seed production in trees are key to understand evolutionary pressures that have shaped forests. A global synthesis of fecundity data reveals that while seed production is not constrained by a strict size-number trade-off, it is influenced by taxonomy and nutrient allocation.

The Pharma Proteomics Project generates the largest open-access plasma proteomics dataset to date, offering insights into trans protein quantitative trait loci across multiple biological domains, and highlighting genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks.