Search

Integration of multi-omics data is challenging due to high dimensionality and non-linear relationships. Here, authors develop an unsupervised method that leverages UMAP embeddings and density-based clustering to integrate diverse omics data types and identifies biologically meaningful patterns across multiple benchmarks.

Researchers mimic protein interface helices by stapling peptide side chains, or replacing hydrogen bonds with covalent ones, and synthetic helical mimics are heavily biased towards stapling. Here the authors describe bioinformatic discovery of hydrophobic triangles at helix N-termini, and rigid, bicyclic synthetic mimics of them.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

A method to introduce defined mutations into the yeast genome enables saturation mutagenesis of a gene and genome-scale introduction of genetic variants.

Two ‘outrigger’ telescopes were added to CHIME, leading to the localization at detection of FRB 20210603A. The burst originated from deep within the star-forming disk of its host galaxy.

Donors spins in silicon are coherent, high-performance qubits, but scale-up has been challenging. Here the authors present the first experimental demonstration of exchange-based, entangling two qubit gates between electrons bound to ³¹P donors in Si.

A pan-cancer genomic analysis finds an increase of extrachromosomal DNA (ecDNA) in treated and metastatic tumors compared to primary, untreated samples, as well as ecDNA features enriched in advanced disease.

Single-cell genomic and transcriptomic analyses of longitudinal samples of patients with Richter syndrome reveal the presence and dynamics of clones driving transformation from chronic lymphocytic leukemia years before clinical manifestation

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Searching online to evaluate the truthfulness of false news articles increases the probability of believing the false news articles.

Large extrachromosomal DNAs are engineered using a CRISPR- and Cre–loxP-based approach and shown to drive cancer in mouse models, with potential applications in determining the role of oncogene amplifications in human cancers.

Arctic marine ecosystems have experienced significant change through the Holocene. Here, the authors used sedaDNA from Northern Greenland to reconstruct marine mammal occurrence, demonstrating the impact of air temperature and sea ice cover over the past 12000 years.

Here, the authors perform a genome-wide association study of fetal haemoglobin (HbF) levels in Africans with sickle cell disease replicating known loci, identifing 14 candidate loci, and highlighting FLT1’s role in hypoxia-associated HbF induction.

In this work, the authors demonstrate a 2D memristor with high switching speeds of 120 ps and study its dynamic response with 3 ns short voltage pulses using statistical analysis, simulation, and modeling.

The assembly of the durian genome provides insights into the unique flavor profile of this tropical fruit. Transcriptome and metabolome analyses show that methionine γ-lyase is upregulated and that volatile sulfur compounds are produced during ripening.

Using single-nucleus RNA sequencing data from patients with sporadic amyotrophic lateral sclerosis (ALS) cortices, the authors find that higher expression of ALS risk genes is accompanied by upregulation of stress responses in groups of extratelencephalic neurons. Analyses of glial nuclei revealed a downregulation of myelination genes in oligodendrocytes and upregulation of reactive state genes in microglia.

The authors analyze how sequencing depth, choice of control sample, paired-end versus single-end reads and the selection of peak-calling algorithm influence the interpretation of chromatin immunoprecipitation–sequencing (ChIP-seq) experiments.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Many neurotransmitters act on receptors coupled to GTP-binding G proteins. Here authors report the structure and activity of a mutant that locks the nucleotide-free and receptor-bound state of the G protein, leading to a rare neurological disorder.

The off-target effects of CRISPR-Cas9 are thought to be mediated by its cognate guide RNA. Here the authors show that Cas9 independently interacts with the human transcriptome, correlating with elevated RNA editing even under guide RNA co-expression.

Generalizable prediction of RNA secondary structure remains a challenge on unseen families. Here, the authors propose BPfold, which integrates a base pair motif library with thermodynamic energy into a deep learning framework, gaining superior accuracy and robustness over state-of-the-art methods.

Spin–orbit torques in heavy metal/ferromagnetic layers have a complex dependence on the magnetization direction. This dependence can be exploited to increase the efficiency of spin–orbit torques.

Sears and colleagues found that ongoing replication stress pathways and T cell clonal responses differentiate liver and lung recurrence and are associated with different clinical outcomes in the context of pancreatic ductal adenocarcinoma.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

CRISPRai simultaneously activates and represses two genes in single cells.

δ-Opioid receptors (δOR) are promising targets for pain management with reduced side effects. Here, the authors use a structure-based approach to design and characterize C6-Quino, a selective δOR partial agonist, highlighting its potential therapeutic relevance.

Interplay of western diet and gut microbiota has been reported to be involved in the development of nonalcoholic steatohepatitis (NASH). Here the authors report that Blautia producta and 2-oleoylglycerol are bacterial and metabolic mediators that promote liver inflammation and hepatic fibrosis in male mice.

Studying changes in the metabolic properties of kidney cancer in patients reveals an increased need for mitochondrial metabolism as tumors metastasize from the kidney to distant organs.

A multicore analogue in-memory computing chip that is designed and fabricated in 14 nm complementary metal–oxide–semiconductor technology with backend-integrated phase-change memory can be used for deep neural network inference.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Ju et al. show that during three-dimensional cell migration, compression recruits cytoplasmic linker-associated proteins to microtubules; these stabilized microtubules then coordinate nuclear positioning and contractility in confined migration.

Analysis of single-nucleus RNA sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing data derived from synovium of patients with rheumatoid arthritis identifies regions with dynamic accessibility that correlate with cell states. Dynamic peaks are more strongly enriched for autoimmune disease heritability.

Acquiring biomarkers from blood or sweat is limited by invasiveness or biofouling. Skin gas emissions bypass these issues, offering rich biosignals. Authors present passive sensing strategies capturing water vapor (Sweat rate), CO2, and VOCs, enabling real-time tracking of physiological changes.

This study demonstrates that orange carrot was selected during the Renaissance period, probably in western Europe, through the selection of three recessive genes that increased the provitamin A carotenoid (α- and β-carotene) content.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.

Here the authors investigate the interactions between genetic perturbations and segregating loci on a genome scale in yeast using barcoded CRISPRi. Strains’ responses to perturbations are shaped by perturbation-locus interactions that cannot be measured by examining perturbations or natural variation alone.

BRAF or MEK1/2 inhibitors are cytostatic in melanoma and the surviving cells develop drug resistance. This study shows that the pro-survival pool is biased towards MCL1 in melanoma so that BRAF or MEK1/2 inhibitors are synthetic lethal with the MCL1 inhibitor AZD5991, improving tumour growth inhibition.

The enzyme SPO11 has a crucial role in meiosis, the process that forms sperm and egg cells. The activity of purified SPO11 has now been reconstituted in a cell-free system — enabling the enzyme’s role to be studied in detail.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Using a globally distributed standardized aerial sampling of fungal spores, we show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude.

DNA sequence preferences or statistical positioning of histones has not explained genomic patterns of nucleosome organisation in vivo. Here, the authors establish DNA shape/mechanics as key elements that have evolved together with binding sites of DNA sequence-specific barriers so that such information directs nucleosome positioning by chromatin remodelers.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Evolink, a method developed to co-evolve structurally adjacent but sequence-distant sites in molecular machines, was used in concert with computational modeling to evolve an improved tethered ribosome variant.

A universal method enables high-specificity, unbiased pathogen detection from diverse body fluids using metagenomic sequencing and may accelerate clinical decisions.

Analysis of data from multiple instruments reveals a giant exoplanet in orbit around the 0.2-solar-mass star TOI-6894. The existence of this exoplanetary system challenges assumptions about planet formation and it is an excellent target for atmospheric characterization.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.