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Mutual paracrine regulation of the cytokines GREM1 and SPP1 mediate mesenchymal and epithelial cell fate in pancreatic cancer.

The authors report a computational framework for determining the meiotic/mitotic origin of nondisjunction (NDJ) in trisomies without parental data. Applying this to Down syndrome, they uncover links between NDJ error stage and leukemia genomics.

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.

3D brain atlases enable spatial data integration across studies. Here, the authors present the Developmental Mouse Brain Common Coordinate Framework, a 3D multimodal atlas from embryonic to adult ages for cell type mapping through brain development.

An analysis of research papers and citing patents indicates the extensive ties between computer-vision research and surveillance.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Acute lymphoblastic leukemias (ALL) with an ETV6::RUNX1 fusion comprise the largest subtype of this cancer, and their optimal treatment strategy remains unclear. Here, the authors perform genomic profiling of 194 ETV6::RUNX1-rearranged pediatric ALL cases, finding two molecular subtypes associated with distinct drug sensitivities.

Integration and comparison of multiple single cell sequencing datasets can be used to compare different studies. Here the authors propose MetaTiME which compares the gene expression of single cells from the tumour microenvironment across different tumours and uses transportable labels and metacomponents to annotate cell types and states.

Cell type epigenetic and topographic information of primate brain is lacking. Here, authors identified transcriptional regulatory network, gradient expression pattern and disease vulnerability at cell type level in PFC, M1 and V1 of monkey brain by snRNAseq, snATAC-seq and Stereo-seq.

BARseq interrogates the expression of 104 cell-type marker genes in 10.3 million cells over nine mouse forebrain hemispheres to reveal the role of peripheral inputs on cortical area development.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

This study uses epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for neurons dissected from different regions projecting to different targets across the whole mouse brain.

IL-33 induces tertiary lymphoid structures.

An approach combining machine learning and combinatorial chemistry enables the creation and evaluation of ionizable lipid libraries for lipid nanoparticle formulation to effectively deliver messenger RNA to several cells and tissues.

Integrative analysis of single-cell RNA-sequencing datasets across mouse gastrulation and organogenesis identifies cell states and trajectories at successive developmental stages, along with transcription factors that could potentially mediate lineage choices.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Lee et al. demonstrate that Ginkgolide B treatment extends lifespan and enhances healthspan in female mice, including a reduction in tumor incidence, enhancement in muscle quality and function and suppression of systemic inflammation and senescence.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

The immunological parameters that define severe influenza disease are not clear within human real time infections. Here the authors compare a severe influenza infection cohort with an influenza vaccinated cohort to understand correlates of severe influenza disease.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Drug-target residence time is viewed as a predictor of the clinical efficacy of small-molecule drugs. A pharmacodynamic model, taking into account the target binding kinetics of antibacterial compounds, leads to accurate predictions of cellular and in vivo efficacies of the inhibitors.

Kedzierska et al. report an association between low production of receptor-binding domain antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities, and show that this condition disproportionately affects Australia’s First Nations peoples because of the high burden of comorbidities in this population.

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 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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

This study on the central San Andreas Fault shows how its fine-scale structures and kinematics, resolved using high-quality focal mechanisms of small earthquakes, are influenced by a weak, poorly coupled fault zone.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Analysis of genomic and clinical features of acute erythroid leukemia in comparison to other myeloid disorders supports its distinct classification, defines subgroups and suggests therapeutic vulnerabilities.

Synchronised neuronal activity is essential for cortical function, yet mechanistic insights into this process remain limited. Here, authors use a combination of in vivo imaging and targeted whole-cell recordings to demonstrate that Somatostatin neurons, in the superficial layers of the mouse primary visual cortex, exhibit functional heterogeneity and can be classified into two distinct subtypes characterized as either having type I uncorrelated, or type II highly correlated with network activity.

The auditory striatum, the tail portion of dorsal striatum, is implicated in decision-making. This study uncovers a phasic mechanism within the nigrostriatal system that regulates auditory decisions by modulating ongoing auditory perception.

Fruitflies require Sestrin to regulate mTORC1 signalling in response to dietary leucine, survive a diet low in leucine, and control leucine-sensitive physiological characteristics, which establishes Sestrin as a physiologically relevant leucine sensor.

FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing.

A cross-reactive antibody and T cell response is identified in a large portion of patients with multisystem inflammatory syndrome in children.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

From modern seasonal to the deep time, global data show that continental hydrology has a direct and consistent effect on river and marine Li isotope compositions, highlighting a crucial role of climate on Earth’s weathering and the carbon cycle.