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Ipecac alkaloids are plant-derived compounds historically used to induce vomiting. Here the authors elucidate how two evolutionary distant plant species have evolved to produce the same ipecac alkaloid.

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.

A model in mouse using a species-adapted virus recapitulates features of SARS-CoV-2 infection and age-related disease pathogenesis in humans, and provides a model system for rapid evaluation of medical countermeasures against coronavirus disease 2019 (COVID-19).

This study identifies a novel immune checkpoint in senescent cells that is linked to the ganglioside GD3 and that contributes to the evasion of immune clearance by these cells and to aging and age-related diseases.

Here, the authors perform a genome-wide association study of the ALPS-index, identifying 17 unique genome-wide significant loci, unraveling mechanisms of brain glymphatic activity and providing insight for its relation to neuropsychiatric phenotypes.

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.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

A large study of impulsivity in 14-year-olds finds that substance use and ADHD symptoms are associated with different brain networks that inhibit motor responses. Genetic analysis implicates the noradrenergic system in activity levels in one of these networks, which is centered on the right frontal cortex.

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.

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.

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.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

The incorporation of nitrogen in steroidal glycoalkaloids is hypothesized to occur through a transamination reaction. Here, the authors show that GLYCOALKALOID METABOLISM12 appears to evolve from the canonical γ-aminobutyric acid transaminases and directs the biosynthesis of nitrogen-containing steroidal metabolites in Solanum plants.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

The impact of tumour heterogeneity on metastatic potential in prostate cancer remains poorly understood. Here, the analysis of single nuclei RNA sequencing and whole-genome sequencing from samples from five patients suggests an interplay between clonal evolution and cellular plasticity driving metastatic seeding.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Iridoids are terpenoid metabolites found in thousands of plants. Using single-cell transcriptomics, the authors discovered an unexpected enzyme that has been neofunctionalized to catalyse the cyclization required to form the iridoid scaffold.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

Late-life cognitive dysfunction is common, but the biological substrates are largely unknown. Here, the authors examined a panel of 90 neurology-related protein biomarkers and show that plasma levels of 22 of these proteins are associated with general fluid cognitive ability in later life.

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.

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.

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.

In this randomized controlled trial, Gennetian et al. evaluated the impacts of cash transfers on family investments. Families with low income were randomized to receive monthly unconditional cash starting at childbirth. Households spent more money and time on child-specific goods and learning activities.

The Muscle Aging Cell Atlas presents approximately 200,000 single-cell and single-nuclei transcriptomes from 17 human donors across different ages, uncovering mechanisms of aging in muscle stem cells, myofibers and microenvironment cells, and demonstrates parallels in mouse muscle aging.

Estimates of infection rates from the UK COVID-19 Infection Survey may have been biased by the characteristics of people who chose to take part. Here, the authors show that the survey population had unusually high vaccination rates and adjust infection estimates taking this into account.

Military personnel face increased exposure to pandemic-related stressors, yet their mental health impacts remain underexplored. Here, the authors analyze data from the STARRS Longitudinal Study, revealing significant increases in mental health issues among soldiers during COVID-19, particularly among vulnerable groups, underscoring the need for targeted support during pandemics.

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.

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

Delivery of human immunodeficiency virus (HIV) testing, treatment and adherence support integrated into sexual and reproductive health services for youth in Zimbabwe did not improve population-level HIV viral suppression over standard care, largely due to a substantial proportion of youth with undiagnosed HIV—highlighting implementation challenges to achieve UNAIDS 90-90-90 targets.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

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.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Knowledge can impact children’s emotion, cognition, and action. The authors show that when seeking information, children consider if information is useful, positive, and lowers uncertainty, with the emphasis on these considerations changing with age.

Harasimov, Gorry, Welp, Penir, Horokhovskyi et al. analyse proteostasis in mammalian oocytes and ovaries: the maintenance of oocytes involves exceptional protein longevity, and many of the extremely long-lived proteins decline as the ovary ages.

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.

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.

A ring galaxy is found at a look-back time of 10.8 Gyr. The diffuse stellar light outside the star-forming ring, the ring’s radial velocity and a nearby intruder galaxy indicate that this is a collisional ring galaxy.

Bhatia et al. evaluate the ability of draining vein liquid biopsy to identify RAS-MEK pathway somatic genetic variants within children and young adults with extracranial arterio-venous malformations (AVMs). They demonstrate the effectiveness of using liquid biopsy to genotype extracranial AVMs in children.

The authors find subtype-specific influenza cross-reactivity patterns, including rapid declines for A(H3N2) within 6 years, sustained responses for A(H1N1)pdm09 and increased cross-reactive responses in humans after repeated A(H3N2) exposure.

This research investigates aperiodic neural activity in depressed individuals versus healthy controls using resting state electroencephalography recordings. Findings reveal significant differences in aperiodic exponent and offset, influenced by lifetime depressive episodes, highlighting the relationship between depression heterogeneity and neural mechanisms.