Search

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.

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.

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.

Autologous transgenic epidermal stem cell cultures are used to reconstitute almost the entire epidermis of a patient with severe junctional epidermolysis bullosa.

This work shows the two independent structures of cardiac amyloids formed by non-native atrial natriuretic peptide (ANP) dimers extracted from atrial fibrillation patients. These data point at dimeric ANP forms as the amyloidogenic species in vivo.

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.

Employing a candidate gene approach, Mancina et al. identify a genetic variant of the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene that reduces susceptibility to fatty liver disease. Functional studies in vitro and in vivo demonstrate that targeting PSD3 protects against fatty liver disease.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

Here the authors show thatMETTL9 enzyme sustains neural development in vertebrates by maintaining the secretory pathway, mainly independently of METTL9 catalytic activity. METTL9 loss in cells leads to Golgi fragmentation.

X-ray polarization measurements of the Crab nebula and pulsar by the IXPE satellite reveal a global toroidal magnetic field with large variations in local polarization, suggesting a more complex turbulence distribution than anticipated.

Scalable platforms for non-invasive action potential recording are needed. Here, the authors present a reliable method to capture APs with patch-clamp-like fidelity from stem cell-derived cardiomyocytes using an Electrolyte-Gated Polymer Field-Effect Transistors.

The application of partitioned polygenic scores to data from cohorts of patients identifies two distinct subtypes of MASLD with different cardiometabolic risk profiles.

IXPE has revealed how the spin of the accreting neutron star Hercules X-1 changes in three dimensions. The spin axis of the star moves both through the star and across the sky, hinting that the crust of the star is asymmetric by almost one part in a million.

Polarization measurements are reported for the blazar Mk501, revealing a degree of X-ray polarization that is more than twice the optical value and supporting the shock-accelerated energy-stratified electron population scenario.

Iron-regulated surface determinant B (IsdB) from Staphylococcus aureus extracts heme from human hemoglobin, which is the first iron transfer step to the bacterial cell. Here, IsdB functional dynamics are explored with X-ray solution scattering techniques including time-resolved WAXS.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

Here the authors show that the dipole-active phonon resonance of semiconducting nanocrystals can be hybridized by a strongly concentrated terahertz vacuum field of a plasmonic nanocavity, thus achieving strong plasmon–phonon coupling even in the absence of direct terahertz illumination.

A study reports the measurement of the polarization degree and angle of X-rays from Sagittarius A^* reflected off a nearby cloud, indicating an X-ray flare about 200 years ago.

In June 2022, the IXPE satellite observed a shock passing through the jet of active galaxy Markarian 421. The rotation of the X-ray-polarized radiation over a 5-day period revealed that the jet contains a helical magnetic field.

Phylogenetic analysis is used to identify transmission chains, but no software is available for the automated partition of large phylogenies. Prosperiet al. apply a new search algorithm to identify transmission clusters within the phylogeny of HIV-1gene sequences linking molecular and epidemiological data.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

The addition of molecules on a magnetic film has been known to alter the magnetic properties of the film. Here, through a combination of density function theory calculations, and magnetic force microscopy measurements, Benini and coauthors show the critical importance of long range correlations in the resulting properties of the molecule-decorated magnetic film.

Polarization can exceed 60% at the leading edge of the inner part of the Vela pulsar wind nebula; in contrast with the case of the supernova remnant, the electrons in the pulsar wind nebula are accelerated with little or no turbulence in a highly uniform magnetic field.

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.

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.

X-ray polarimetry observations with the Imaging X-ray Polarimetry Explorer constrain the accretion geometry in an X-ray pulsar and provide evidence for a misalignment of the spin, magnetic and orbital axes in Her X-1.

Here, the authors present paleogenomics, dental histology, geochemistry, radiocarbon dating, and bioarchaeological analysis of an Upper Palaeolithic infant from Grotta delle Mura (southern Italy). These data depict the health and development of the individual and point to regional population turnover at the time.

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.

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.

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.

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.

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.

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.

This study presents a method to create nanoscale polarization transient gratings in the EUV range. Unlike intensity gratings, it reduces thermal effects, revealing hidden material dynamics. This enables new insights in chiral materials and ultrafast magnetism.

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.

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.

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.

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.

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.

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.

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

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.

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.

This Review summarizes our current knowledge about the genetic underpinnings of metabolic-dysfunction-associated steatotic liver disease and highlights its causal association with type 2 diabetes and insulin resistance.

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.