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Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Glioblastoma (GBM) is an aggressive tumor characterized by an immunosuppressive microenvironment. Here, the authors present a therapeutic approach based on the implantation of a biodegradable scaffold for the sustained, local release of a TLR7/8 agonist at the time of tumor resection, to achieve anti-tumor immunity and protection from future tumor challenge.

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.

Erlich et al. show that soluble LTα and membrane-bound LTα1β2 lymphotoxins expressed by B cells play distinct roles to attenuate the pathology observed in ileitis.

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.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

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.

People living in rural areas of the United States have poorer outcomes from acute COVID-19. Here, the authors show that higher mortality rates among rural dwellers persist for up to two years after the initial infection, even after accounting for baseline risk factors.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

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.

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.

Vaccination against one viral strain can result in cross-reactive antibodies against another viral strain. In this study, the vaccination of mice against the 2009 H1N1 virus is shown to protect mice from the 1918 Spanish influenza virus, which resulted in millions of deaths worldwide.

The photosynthetic production of oxygen in the ocean is thought to have begun at least 2.7 billion years ago. The geochemistry of marine sediments deposited 2.6 billion years ago suggests that ocean margins were oxygenated at least 100 million years before the first significant increase in atmospheric oxygen concentrations.

BioID detection of Ebola virus–host interactions when computationally integrated with existing host protein-protein networks, revealed functional cell protein complexes supporting infection, including the RNA decapping complex.

The authors discuss the dysregulated host response in sepsis and the use of biomarkers to gauge the immunological status of patients and potentially guide precision medicine. They also highlight potential immunomodulatory therapies for sepsis and discuss the future of sepsis clinical trials.

Studies in humans and mice show that myocardial infarction recruits monocytes to the brain’s thalamus, promoting sleep, which in turn restricts cardiac inflammation and sympathetic signalling and assists healing.

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

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

Radiometric dating and oxygen isotopes of Pilbara Craton zircons reveal early continent formation via seafloor hydrothermal alteration and subsequent shallow depth partial melting of mafic protcrust some 3565 million years ago.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

McGavern and colleagues identified a CD8⁺ T cell population that expresses GZMK in ʽtau-richʼ brains, where it may play a protective role against neurodegeneration.

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.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Anandasabapathy and colleagues show that the inhibitory receptor PD-1 impacts the specification of tissue-resident memory T cells in the skin.

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.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

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.

This study establishes how aperiodic activity, a ubiquitous signal linked to neural noise, develops in localized brain regions and illuminates the development of prefrontal control during adolescence in the development of attention and memory.

Wnt signaling functions in tissue homeostasis and tumorigenesis. Here the authors show that ROR2, a Wnt receptor, plays roles not only in transducing Wnt signaling, but also in regulation of DNA damage response critical for stem cell maintenance.

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.

Single-cell proteomic and transcriptional profiling of atherosclerotic lesions from human carotid arteries reveals specific features of lesional T cells and macrophages associated with symptomatic disease.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

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 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.

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.

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.

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.

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.

The Mid-Cayman Spreading Centre is an ultraslow-spreading mid-ocean ridge in the Caribbean. This study reveals two hydrothermal vent fields on the ridge, including high-temperature vents on an off-axis oceanic core complex where, similar to Mid-Atlantic vents, an alvinocaridid shrimp is common at both vent fields.

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.

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 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.

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.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.