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Oncolytic viruses, including Zika virus, have been proposed as therapeutic option for glioblastoma (GBM) treatment, however, efficacy in patients remains suboptimal. Here, the authors show that expanding peripheral T cells with long-acting IL7 prior to intratumoral oncolytic treatment improves survival in GBM preclinical models.

Jacquemyn et al. identify key lipid determinants controlling ectosome shedding from neurons. They find that ectosomes are a major route for the intercellular transport of misfolded α-synuclein, with relevance to Parkinson’s disease pathology.

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.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Battery electrode binders are hard to image but strongly affect battery performance. Here, authors use silver and bromine staining to reveal common cellulose- and rubber-based binders in graphite and Si negative electrodes and identify processing that reduces electrode resistance.

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.

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.

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.

Breeding crops with delayed senescence could plausibly increase grain yield. Here the authors show that variation at the rice SGR locus contributes to differences in senescence between indica and japonica subspecies and show that introgression can increase yield in an elite indica rice variety.

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.

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.

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.

The authors developed a microfluidic device, FIND-Chip, designed to automate and enhance oocyte recovery from follicular fluid, a process traditionally done manually. When used in clinical settings, the device recovered additional oocytes missed during manual screening, substantially increasing the number of viable oocytes available for in vitro fertilization.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

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.

Application of multiancestry and ensemble-based approaches yields improved polygenic risk prediction models for breast cancer and its subtypes among women of African ancestry.

This research introduces a method for generating customizable spatiotemporal optical vortex (STOV) combs, enabling precise control of light’s spatial and temporal properties. It also demonstrates their application in high-capacity, efficient information transmission systems.

Multi-trait genome-wide analyses identify variants associated with comorbid lung diseases. Polygenic scores leveraging shared components of heritable risk improve prediction of asthma, chronic obstructive pulmonary disease and lung cancer in a multi-ancestry cohort.

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.

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.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

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.

Guided by density functional theory, a commercially viable refractory alloy is developed, which exhibits excellent room-temperature ductility and strength, and high strength at elevated temperatures.

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.

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.

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.

Multi-omics and genetic models show that CGG repeat toxicity in GABAergic neurons drives FXTAS pathology and identify PRKCG as a critical modifier and potential therapeutic target.

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.

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.

Increasing dietary carbohydrate-to-fat ratio in a randomized controlled feeding study altered circulating small molecules (metabolites), including ones associated with diabetes risk, underscoring important metabolic effects of dietary composition.

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.

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 meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

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.

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

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.

Asthma exacerbations remain hard to predict with routine tests. Here, the authors show that simple blood sphingolipid-to-steroid ratios predict five-year exacerbation risk and can underpin a practical, low-cost assay that outperforms standard clinical measures.

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.

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.

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.

It remains elusive whether the T cell repertoire will cover all point mutations of a major epitope. The authors here show that COVID vaccine–induced CD8⁺ T cells detect most YLQ peptide variants except R5, but naïve T cells fill this gap by responding to R5 despite abundant WT-specific cells, ensuring broad coverage to prevent viral immune-escape.

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.

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.

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.

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.