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One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

High-resolution geospatial mapping found that the annual incidence of cholera shifted from western to central and eastern Africa between 2011 and 2020, with the latter regions more likely to report cholera in 2022–2023, reflecting instability in cholera burden patterns that can impact progress in disease control.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

The study proposes a diversity-aware population modeling framework that can guide targeted strategies in public health, using Bayesian multilevel regression and post-stratification to quantify sociodemographic disparities in cognitive development.

Chronic stress is a risk factor for depression, yet the mechanisms are unclear. Here, the authors show in mice that stress drives interferon-mediated neutrophil recruitment from the skull to the brain’s outer membranes, contributing to depressive behaviors.

Magnesium hydride is a potential hydrogen-storage material, but its use is hampered by its high stability and slow hydrogen sorption processes. Dimeric magnesium compounds can act as models for these materials, and it is now shown that they can be easily and reversibly hydrogenated across the magnesium–magnesium bond.

Analysing the distributions of >99% of the world’s seed plant flora, the authors find evidence supporting the evolutionary imbalance hypothesis, with species originating from large, biodiverse regions being more successful at naturalizing beyond their native ranges.

Combining neuroimaging, physiological and behavioural methods, Meissner et al. show that humans can self-regulate the brain’s arousal levels via a biofeedback approach that is based on measurements of the eye’s pupil.

Kalium channelrhodopsins (KCRs) are promising tools for optogenetic silencing. Here, the authors show that KCRs inhibit cellular excitability in flies, worms, and fish, establishing them as first-line tools for inhibiting diverse types of excitable cells.

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.

Mohanty et al. examine the link between county-level Minority Health Social Vulnerability Index and rates of all-cause pneumonia, pneumococcal pneumonia, and invasive pneumococcal disease from 2016 to 2019 among publicly insured U.S. adults. Findings show that pneumococcal disease rates are higher in the most socially vulnerable counties.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

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 coding variant of the PAX4 transcription factor (p.Arg192His) is uniquely associated with Type 2 Diabetes in East Asian populations. Here, the authors show that two different coding gene variants of PAX4, p.Arg192His and the newly identified p.Tyr186X, can influence pancreatic beta cell development, identity, and function.

Pooled and sex-specific genome-wide association analyses identify new risk loci for restless legs syndrome and candidates for drug repurposing. Machine learning models combining genetic and other information show improved risk prediction performance.

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.

Here, the authors conduct a paired genome analysis of humans and Mycobacterium tuberculosis in a cohort from Lima, Peru. Their research reveals that genetic variations in both the host and pathogen significantly influence the progression to tuberculosis.

Ruth Loos and colleagues use genome-wide association to identify common variants influencing body fat percentage. Unexpectedly, they show that a body-fat–decreasing allele near IRS1 is associated with an impaired metabolic profile, including increased risk of type 2 diabetes and coronary artery disease.

Multi-ancestry genome-wide association analyses and systematic variant-to-gene mapping strategies implicate new genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.

The analysis of essential genes in pathogens can be used to discover potential antimicrobial targets. Here, the authors use a machine learning model and chemogenomic analyses to generate genome-wide gene essentiality predictions for the fungal pathogen Candida albicans, define the function of three uncharacterized essential genes, and identify the target of a new antifungal compound.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Disentangling the impacts of non-pharmaceutical interventions on COVID-19 transmission is challenging as they have been used in different combinations across time and space. This study shows that, early in the epidemic, school/daycare closures and stopping nursing home visits were associated with the biggest reduction in transmission in the United States.

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.

An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.

A genome-wide association study in more than 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, transancestral cohorts.

Activity patterns in the hippocampus resemble temporal relations of learned event sequences. Here, the authors show that these relational memories arise through mnemonic construction and are generalized to reflect the temporal event structure.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

APOE4 is produced by neurons under stress, but the role of neuronal APOE4 in Alzheimer’s disease pathogenesis is still unclear. Here the authors report that selective removal of neuronal APOE4 in tauopathy mice mitigates many prominent Alzheimer’s disease-related pathologies.

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.

This study shows that assignment to a time-of-use rate disproportionately increases electricity bills for elderly and disabled households, and is associated with worse health outcomes for disabled and ethnic minority households, exacerbating existing injustices for vulnerable groups.

Interpreting untargeted mass spectrometry (MS) data is challenging due to incomplete reference libraries. Here, the authors created the nearest neighbor suspect spectral library from largescale public MS data, significantly enhancing the ability to hypothesize structures for unknown mass spectra.

Abnormal functions of RNA-binding proteins TAF15, FUS and TDP43 are associated with amyotrophic lateral sclerosis. Here, Kapeli et al. characterize the RNA targets of TAF15 and identify points of convergence and divergence between the targets of TAF15, FUS and TDP43 in several neuronal systems.

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.

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

Engineered kill-switch-encoding Mycobacterium tuberculosis infects, elicits immune responses and is cleared from immunocompetent and immunocompromised mice, providing a model of controlled tuberculosis infection.

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.

Enhancer of zeste homolog 2 (EZH2) has been implicated as a driver of disease progression and resistance to hormonal therapies. Here, the authors focus on EZH2 in two subtypes of advanced prostate cancer and report how it modulates the bivalent genes thereby leading to forward differentiation after being targeted in neuroendocrine prostate 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.

Selective neurodegeneration is a critical causal factor in Alzheimer’s disease. Zalocusky et al. demonstrate a causal chain linking neuronal ApoE expression to MHC-I expression and, subsequently, to tau pathology and selective neurodegeneration.

The ability to delay gratification in childhood correlates with the ability to exert self-control in adulthood. Berman and colleagues re-examine individuals that were studied 40 years ago and find that the individuals who are able to exert a high level of self-control have more efficient neural networks.

A framework combining combinatorial CRISPR knockout in breast, lung and oropharyngeal cancer in vitro models with public data identifies synthetic lethal interactions, such as perturbed KDM5C sensitizing cells to PARP7 inhibition.

Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.

The costimulatory T-cell receptor 4-1BB is an immuno-oncology target. Here the authors present the ligand bound 4-1BB receptor crystal structure in addition to the structures of 4-1BB bound with two therapeutic antibodies and verify the antibody binding sites by mutational analysis, which is of interest for further 4-1BB therapeutics development.

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.

Responses to SARS-CoV-2 vaccines in different populations are important to define efficacy. Here the authors show using a cohort in Singapore that two doses of mRNA vaccine is less effective in recipients over 60 years of age and that a further dose of vaccine can improve these antibody levels.