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The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

This study uses brain recordings, self-reports, and facial analysis to decode acute pain in epilepsy patients. Machine learning reveals stable neural markers in mesolimbic, striatal, and cortical regions, plus facial cues, enabling reliable pain detection in naturalistic settings.

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.

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.

Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

The deactivation of CO₂ reduction electrocatalyst in microbial media remains a key barrier for hybrid bio-electrochemical systems. Here, the authors present a bioadaptive nickel single atom catalyst that resists organic poisoning to enable high-rate CO-mediated isopropanol production from CO₂.

Pyramidal neuron-driven mechanisms actively promote the survival and terminal differentiation of their associated interneuron subtypes.

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.

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

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.

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.

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

Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.

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 work, researchers show how laser annealing is used to create complex 2D gradients in magnetic properties, which can steer spin waves and domain walls. This fast, maskless method enables the development of next-generation computing devices.

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 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.

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.

A simple transport model infers a material’s electronic dimensionality from standard transport measurements, revealing temperature-, doping- and alloying-driven shifts between low-dimensional and 3D transport in SrTiO₃, Bi₂O₂Se and Pb_1-xSn_xTe.

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.

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.

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.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

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.

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.

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.

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.

This Perspective reviews tools developed over the past five years in the macromolecular modeling, docking and design software Rosetta.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Transparent photodetectors based on graphene stacked vertically along the optical axis have shown promising potential for light field reconstruction. Here, the authors develop transparent photodetector arrays and implement a neural network for real-time 3D optical imaging and object tracking.

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.

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.

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.

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.

In the absence of progranulin, microglia enter a disease-specific state that causes endolysosomal dysfunction and neurodegeneration, and these microglia promote TDP-43 granule formation, nuclear pore defects and cell death specifically in excitatory neurons via the complement activation pathway.

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.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

LEVA is a label-free immobilization method for studying surface-bound extracellular vesicles.

Aromaticity predicts the existence of the benzene tetra-anion, although it has not been unambiguously observed. Here, the authors have synthesized a tetra-anionic substituted benzene as a ligand and characterize the six-carbon, 10 π-electron system by structural, spectroscopic and theoretical techniques.

Correlated errors coming from leakage out of the computational subspace are an obstacle to fault-tolerant superconducting circuits. Here, the authors use a multi-level reset protocol to improve the performances of a bit-flip error correcting code by reducing the magnitude of correlations.

S receiver function data reveal distinctive mantle gradients at 75-km and 180-km depths near the Rocky Mountains, suggesting a dual-lithosphere architecture in which the Cordillera is underthrust by Precambrian craton core.