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Translation initiation and elongation factors can be targets for cancer treatment. Here, the authors show that inhibiting translation elongation through eIF5A impairs mitochondrial function, slowing the proliferation of tumour cells.

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.

A global research network monitoring the Amazon for 30 years reports in this study that tree size increased by 3% each decade.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

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.

Bayesian psychophysical modelling of cardiac and respiratory interoception (N=241) showed no cross-domain associations in sensitivity, precision, or metacognition, indicating that interoceptive performance is organ-specific.

The predicted increase in frequency of droughts and rising temperatures in Europe will lead core populations of a temperate plant to an evolutionary dead-end unless they acquire genetic alleles that are present only in extreme edge Mediterranean, Scandinavian, or Siberian populations.

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.

This flagship study from the European Solve-Rare Diseases Consortium presents a diagnostic framework including bioinformatic analysis of clinical, pedigree and genomic data coupled with expert panel review, leading to 500 new diagnoses in a cohort of 6,000 families with suspected rare diseases.

Chemically induced protein degradation is a powerful alternative to classical inhibition, but some proteins have deeply masked binding pockets that make the development of degrader molecules difficult. Here, the authors discover an alternate site on nuclear receptors that can be targeted by degraders.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

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

Globalization has accelerated the spread of mosquito species that transmit human diseases. This global analysis reveals that 45 disease-vector mosquito species have been introduced to non-native regions worldwide, mostly after 1950 with 12 new species recorded outside their native ranges since 2000.

Metabolomic profiling of 581 mother–child pairs revealed patterns associated with neurodevelopmental disorders (NDD). Maternal metabolomic profiles at gestational week 24 showed the strongest predictive value, with quinolinate consistently associated with NDD across time points and linking maternal inflammation to NDD risk.

In this study, the authors develop a flavivirus vaccine strategy by introducing mutations into envelope glycoproteins resulting in structural changes that conceal the ADE-prone fusion loop epitope. They show that the Zika virus-specific construct protects mice against viral challenge and prevents ADE by Dengue virus.

The metastatic potential of patients following breast cancer neoadjuvant therapy is highly variable. Here, the authors demonstrated the predictive and prognostic value of ctDNA in 723 patients with high-risk early-stage breast cancer using serial analysis.

H5N1 avian influenza viruses caused an outbreak in dairy cattle. We show that the potential for avian viruses to replicate in cow cells varies across H5N1 evolution, suggesting that the risk of spillover into mammals differs between variants.

Methods used to date a network of marine sediment cores reveal that rapid retreat of the Ross Ice Shelf was contemporaneous with the lowering of nearby outlet glaciers, implicating warm ocean waters as a driver of Antarctic deglaciation.

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 QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Authors demonstrate that four distinct heterodimeric complexes catalyze chondroitin sulfate chain polymerization in humans. The synthase proteins possess catalytic activity, while the polymerization factors are essential for complex formation.

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.

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.

The authors optimize an in vitro human epiblast model, which they utilize to show that early TGFβ family inhibition prevents epithelial identity, whereas it is dispensable after epithelium formation. These phenomena are conserved in mice.

Repeated stress triggers habituation, an important stress coping response. Here, authors chart the dynamic gene expression changes that underlie stress habituation in the mouse brain and reveal two distinct molecular mechanisms behind this process.

Here they show that PPARα-dependent mitochondrial programming promotes the differentiation of pluripotent stem cell-derived β cells. Targeting mitochondria has the potential to improve β cell replacement efforts for the treatment of type 1 diabetes.

Merlino et al. demonstrate that the cytokine Interleukin-27 contributes to innate antiviral immunity in the placenta and is an important defense against congenital Zika virus infection.

Myocardial infarction disrupts cardiac repair mechanisms, limiting regeneration. Here, the authors show that extracellular matrix therapies activate spatial and cell-specific pro reparative programs, revealed through spatial transcriptomics and snRNA-seq.

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.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Here, the authors generated and analyzed run-on sequencing data to observe transcription in species across the tree of life to uncover the origins of the promoter-proximal pause.

The planum temporale is a key structure in the human language network. Here the authors show that planum temporale asymmetry at birth in baboons predicts the development of communicative right-hand use, which suggests some common features in the wiring of communicative properties between species.

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.

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.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Combined hormonal therapy and CDK4/6 inhibition face resistance challenges in endometrial cancer. Here, the authors present a phase 2, one-arm clinical trial, where metformin is combined with letrozole (hormonal therapy) and abemaciclib (a CDK4/6 inhibitor) reporting safety and efficacy in patients with endometrial cancer.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

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.

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.

Stress resilience is the maintenance of mental health despite adversity. Here, the authors show that how we typically evaluate adverse events is a key resilience factor and that improving it goes along with improved resilience.

Dengue virus transmission by Ae. aegypti mosquitoes poses a significant public health threat, necessitating innovative control strategies. Here, the authors demonstrate that, while successive blood feeding increases earlier dengue virus dissemination, the inhibitory effects of Wolbachia remain strong, highlighting Wolbachia’s potential to disrupt dengue transmission under natural feeding conditions.

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.

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.

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 recombinant antivenom composed of eight nanobodies provides broad protection against venom-induced lethality and dermonecrosis in mice challenged with venoms from cobras, mambas and rinkhals snakes.