Search

Patient samples are often available in limited amounts, restricting the number of possible omics analyses. Here the authors present MONTE, a workflow that enables serial HLA-I and HLA-II immunopeptidome, ubiquitylome, proteome, phosphoproteome, and acetylome data collection from patient samples.

Life-threatening vascular tumors can be associated with uncontrolled activity of the guanine nucleotide-binding protein subunit alpha (Gαq). Here, the authors develop a murine model for these tumors and show that MEK inhibition prevents formation of vascular lesions and improves survival.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

Changes to actin dynamics during brain aging are not well understood. Here, the authors report that there is an age-related increase in F-actin in Drosophila brain which disables autophagy within the tissue and limits the fly lifespan.

Phage Thoeris anti-defence proteins Tad1 and Tad2 both achieve anti-CBASS activity by simultaneously sequestering CBASS cyclic oligonucleotides.

Functional CRISPR screens in patient-matched pre-treatment and post-treatment glioblastoma models identify the PTP4A–ROBO1 axis as a driver of tumorigenicity and enriched ROBO1 expression in recurrent glioblastoma that can be targeted with CAR T cell therapy.

A systematic review, combined with a stakeholder survey, presents an overview of current practices and recommendations for dataset curation in health, with specific focuses on data diversity and artificial intelligence-based applications.

Here the authors report genome-wide profiling of tRNA modifications using Induro-tRNAseq and uncover coordinated changes across cell types and tissues that underlie the basis of protein homeostasis.

An improved, single-cell lineage-tracing system, based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility, is used to define the clonal architecture of haematopoietic stem cells.

Goldenberg et al. find that people are attracted to social ties who are more politically extreme, rather than moderate. This tendency, called acrophily, is shown to occur when people select ties on the basis of both emotions and attitudes to political issues.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

Ruth Halaban, Michael Krauthammer and colleagues report exome sequencing of 213 melanomas and identify a distinct co-mutation pattern of NF1 with known RASopathy genes. They identify novel melanoma mutations in several RASopathy genes and suggest that mutations in these genes may enhance the pathogenicity of NF1 mutation.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

Progressive supranuclear palsy is a devastating neurological disorder without treatment. Here, the authors leveraged omics data and model organisms to nominate, prioritize, and validate high-confidence candidate genes as therapeutic targets.

Diffraction-before-destruction of ultrashort X-ray pulses can visualize non-equilibrium processes at the nanoscale with sub-femtosecond precision. Here, the authors demonstrate how the brightness and the spatial resolution of such snapshots can be substantially increased despite ionization.

The randomized B-F1RST trial evaluating the clinical utility of blood tumor mutational burden as a predictor of benefit from atezolizumab in patients with advanced lung cancer did not meet its pre-specified primary objective, underscoring the need to further investigate the significance of bTMB as a relevant biomarker for patient selection.

Tan and colleagues conducted a single-cell multiomic analysis of T cell acute lymphoblastic leukemia and identified a treatment-resistant subpopulation of bone marrow progenitor-like blasts associated with poor outcomes.

Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.

Lipid nanoparticle delivery of mRNA vaccines has become of particular importance, however, mRNA stability is a major concern. Here, the authors report on a study of lipid impurity mRNA interactions using reverse phase ion pair HPLC to identify reactions which render the mRNA untranslatable, reducing vaccine efficiency.

In a cohort of 50,556 South Asian individuals, partitioned polygenic scores helped identify genetic susceptibility to insulin deficiency and unfavorable fat distribution as key drivers of young-onset T2D diagnosis and faster progression to diabetes-related complications.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Population differences in immune responses to SARS-CoV-2 can be explained by environmental exposures, but also by local adaptation acting through genetic variants acquired after admixture with archaic hominin forms.

There is an unmet need to improve the response to immune checkpoint blockade in patients with head and neck squamous cell carcinoma (HNSCC). Here the authors show that aberrant HER3 activation sustains the proliferation of PIK3CA wild type HNSCC cells and that HER3 inhibition increases response to PD-1 blockade in HNSCC preclinical models.

It is hoped that quantum computers may be faster than classical ones at solving optimization problems. Here the authors implement a quantum optimization algorithm over 23 qubits but find more limited performance when an optimization problem structure does not match the underlying hardware.

Single-cell transcriptional profiling of primary human synovial sarcoma tumors suggests that combinatorial treatment with HDAC and CDK4/CDK6 inhibitors could enhance tumor immunogenicity.

Peter Campbell and colleagues identify PLCG1 and PTPRB as new driver genes for angiosarcoma through whole-exome sequencing of tumor samples. They find somatic PTPRB mutations in 10 of 39 cases and PLCG1 mutations in 3 of 34 cases, along with mutations in known cancer-related genes.

Empirical analysis of climate change debates in the US Congress shows that policymakers are most likely to seek out experts confirming their existing views. That information then gets disseminated among like-minded individuals in ‘echo chambers’.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Although a number of hypotheses have been put forward to explain the sulphate deposits discovered by the Opportunity rover at Meridiani Planum, Mars, the sedimentary layers remain enigmatic. A re-analysis of the chemistry, sedimentology and geology of the deposits suggests they formed through a reworking of the sublimation residue from a large-scale deposit of ice and dust.

There are distinct hypermethylation patterns in gene promoters in hepatocellular carcinomas (HCCs). Here, the authors show that the enhancer of C/EBPβ is recurrently hypomethylated in human HCCs, recapitulating this in a transgenic murine model and linking aberrant enhancer hypomethylation to hepatocarcinogenesis.

Integrative analysis in patients with diffuse large B-cell lymphoma uncovers that biallelic mutations on TMEM30A are associated with a favorable outcome and enhanced sensitivity to CD47 blockade.

Analysing data from 39 grassland biodiversity experiments, the authors uncover the direct and indirect contributions to ecosystem stability of taxonomic, phylogenetic and functional trait diversity.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

In this work, authors probe the molecular mechanism of re-emerging CHL susceptibility in Malawian Enterobacterales isolates, where they identify a stable truncation of resistance genes by insertion sequences.

Nonalcoholic steatohepatitis (NASH) and dietary cholesterol are risk factors for hepatocellular carcinoma (HCC). Here, the authors utilise mouse models to show that dietary cholesterol induces NASH by deregulating genes involved in metabolism, inflammation and calcium signaling to induce NASH-HCC.

Sea otters recolonizing an estuary in California indirectly reduce erosion by reducing burrowing crab abundance, suggesting that restoring predators could be a key mechanism to improve the stability of coastal wetlands and other ecosystems.

GWAS in difficult-to-recruit populations identifies variants associated with Lassa fever outcome and susceptibility at loci proximal to LIF, GRM7 and LARGE1.

Multi-omic mapping shows that group 3 and group 4 medulloblastomas have a common, human-specific developmental origin in the cerebellar rhombic lip, providing a basis for their ambiguous molecular features and overlapping anatomical ___location, and for the difficulty of modelling these tumours in mice.

Kinases activated by gene fusions represent potentially important targets for the development of cancer drugs. Here, the authors develop a method for detecting gene fusion events in RNA sequencing data from The Cancer Genome Atlas and identify several novel recurrent fusions involving kinases.

Pythium sensu lato (s.l.) is an oomycete that poses a serious threat to agricultural production worldwide. This study, using metabarcoding, provides insights into the diverse soil communities of Pythium s.l. across 127 locations and their disease potential in European corn fields.

EDI048 is a gastrointestinal-targeted Cryptosporidium PI(4)K inhibitor that undergoes a predictable metabolism and limits systemic exposure without compromising its anti-parasitic activity.

Activated B cells and T cells accumulate within joints of patients with rheumatoid arthritis. Here, the authors use single-cell transcriptome and repertoire profiling to identify clonally expanded synovial B cells and T cells and define their phenotypes and predicted cell-cell interactions.