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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.

JWST observed helium and water in the atmosphere of the giant planet WASP-107 b, revealing a vast outflow of gas and evidence for recent inward migration. The findings shed light on how giant planets lose mass and evolve over time.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

Net-zero bioplastics are possible when combined with high recycling rates. This study presents a mixed polyester recycling process integrated with monomer separation and purification for both fossil- and bio-based plastics. Techno-economic and life cycle analyses confirm its environmental and commercial advantages, advancing the path toward circular, low-emission polyester plastics.

Transcriptomic and proteomic analyses show that high levels of the extracellular-matrix protein osteopontin are associated with the attenuated foreign-body response elicited by breast silicone implants wrapped with acellular dermal matrix.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

This systematic review and meta-analysis of 53 randomized controlled trials finds that educational interventions can help students reduce cognitive biases, with a small but statistically significant overall effect.

Schwannomas are regularly treated with radiotherapy, but the molecular effects on these tumours and their microenvironment remain unclear. Here, the authors show that radiotherapy can induce epigenetic reprogramming and immune infiltration in schwannomas, and develop the snARC-seq approach to analyse the epigenomic evolution at the single-cell level.

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.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Here, the authors show that signal transducer and activator of transcription 3 (STAT3) has dual functions in small cell lung cancer as its deletion inhibited primary tumor growth but boosted metastatic spread. These seemingly opposing functions are a result of the requirement of STAT3 for stimulator of interferon genes–interferon signaling in metastasis and the authors show how it can be targeted in mice.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

It is unclear whether plant-herbivore interactions systematically favour exotic plant species. Here the authors investigate plant-herbivore and plant-soil biota interactions in experimental mesocosm communities, finding that exotic plants dominate community biomass despite accumulating more invertebrate herbivores.

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).

Transcriptomic and proteomic analyses of cells and matrix along the fibrotic trajectory in mouse lung identified PI16 as an anti-fibrotic factor with potential for therapeutic application in humans.

Rocks and dust from the asteroid Bennu contain some of the molecular building blocks of life on Earth, such as amino acids and nucleobases. They also carry ammonia that formed billions of years ago in cold, distant regions of our Solar System.

Returned samples from the carbonaceous asteroid Ryugu provide pristine information on the original aqueous alteration history of the Solar System. Here, the authors utilize Breunnerite grain and magnesium isotope chemistry to reveal cation partitioning during aqueous alteration of asteroid Ryugu.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

The atmospheres of white dwarfs often contain elements heavier than helium, even though these elements would be expected to settle into the stars’ interiors; observations of the white dwarf WD 1145+017 suggest that disintegrating rocky bodies are orbiting the star, perhaps contributing heavy elements to its atmosphere.

Ding and colleagues use bulk, single-cell and single-nucleus multi-omics together with spatial transcriptomics and multiplex imaging of clinical tumor samples to characterize gene expression and chromatin accessibility of breast cancer lineages.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

In a non-prespecified interim analysis of a phase 1 trial, autologous PRAME-directed TCR T cell therapy was safe and elicited durable responses in patients with recurrent and/or treatment-refractory PRAME⁺ advanced solid tumors, including melanoma and synovial sarcoma.

VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

Park, Davis et al. evaluate candidate biomarkers of cancer-associated cachexia in a diverse cohort of pancreatic ductal adenocarcinoma individuals. GDF-15 is better at classifying cachexia than standard biomarkers for non-Hispanic White and Hispanic/Latinx individuals, but not for non-Hispanic Black individuals.

Analysis of behaviour, physiology, anatomy and connectomics in Drosophila shows how direction-specific visual information is transformed onto downstream premotor networks and converted into appropriate motor responses.

The authors use US Breeding Bird Survey data to quantify the losses and gains in bird species richness that have not yet been realized owing to ecological time lags following past land use changes.

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.

Combinatorial experimental and bioinformatics methods can be used to analyse function and specificity of CD8 T cells. Here the authors propose a multiomic analysis framework Antigen-TCR Pairing and Multiomic Analysis of T cell (APMAT) to relate TCR specificity to transcriptomic phenotype indicating associations with physicochemical features.

Kelly et al. describe two cerebellum–thalamus–mPFC pathways in mice that regulate social and repetitive behavior. PC activation in Rcrus1 and posterior vermis improved social and reduced repetitive behaviors, respectively, in PC-Tsc1 mutant mice.

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

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.

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.

Multi-Omic approaches are a powerful way for obtaining in-depth understanding of a cell’s state. Here the authors present DISCO, combining digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to analyze single-cell genomes, transcriptomes and proteomes in a mixed population.

Linke et al. use unbiased and quantitative techniques to directly link both known and unknown liver and plasma lipid moieties to specific genomic loci, as compiled in a public web resource, LipidGenie. LipidGenie aided in the identification of a new group of sex-specific phosphatidylcholines.

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.

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.

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.

Negative phases of the Interdecadal Pacific Oscillation, which alters hydroclimatic risk across the Pacific, have been shorter and less frequent than inferred from the instrumental record, suggests a 2,000-year ice core reconstruction.

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.

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.

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.