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Here the authors provide convolutional neural networks (CNN) that can predict antibiotic resistance (MICs) in Mycobacterium tuberculosis with high accuracy and biological interpretability, and show that CNN-predicted sub-breakpoint rifampicin MIC is linked to worse treatment outcomes.

This study found COVID-19 vaccination offers added protection against reinfection in children and adolescents with prior infection but variable effectiveness across variants. Findings support vaccination benefits beyond infection-acquired immunity.

Many hospitalised children with acute illness in low- and middle-income countries experience incomplete recovery, readmission, and post-discharge mortality despite guideline-directed care. Here the authors report multiomic profiling to investigate biological drivers of hospital in-patient and post-discharge mortality in 3,101 acutely ill children across nine sites in sub-Saharan Africa and South Asia.

Integration of data representing 35,120 brain scans from diverse global studies enables construction of reference charts that define normative microstructural and macrostructural properties across the human lifespan for research and clinical diagnosis.

Johanns and colleagues report the results (including safety, efficacy and immunogenicity) of a phase 1 clinical trial of a DNA-based personalized therapeutic cancer vaccine administered following surgical resection and radiation in patients with MGMT unmethylated glioblastoma.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Tanycyte-derived extracellular vesicles are shown to regulate feeding diurnality and metabolic balance through insulin precursor-mediated targeting and delivery of mTORC components to hypothalamic neurons.

Sulfation helps shape cartilage, bone and other biological functions. Here, the authors identify MESH1 as the 3′-phosphoadenosine-5′-phosphosulfate-degrading enzyme that controls sulfation in animals and show that blocking MESH1 restores sulfation-linked defects, revealing a potential therapeutic target.

Applying proteomics to longitudinal plasma samples from calorically restricted participants of the CALERIE trial, Mishra, Kim and colleagues link complement protein C3a to inflammaging. In aged mice, visceral fat macrophages produce C3a, and neutralization of C3a blocks inflammaging.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Snyder et al. analyze two population-based birth cohorts to test associations of newborn metabolite concentrations and childhood respiratory outcomes. C4, C10:1, C18:2, and citrulline are associated with early-life wheezing and asthma, with C18:2 specifically associated with increased non-allergic asthma risk.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

Non-linearity leads to remarkably rich physics across a wide variety of length and energy. Here, You and coauthors study the non-linear behaviour of a magnonic system, specifically a synthetic antiferromagnet, where they observe hysteretic mode hopping between the optical and acoustic magnon branches.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

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.

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.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Immune checkpoint inhibitors (ICIs) have shown limited efficacy in recurrent high-grade astrocytoma (rHGA). Here the authors report the results of a Phase 1/randomized Phase 2b trial of laser interstitial thermal therapy followed by anti-PD1 pembrolizumab in patients with rHGA.

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.

Magnon transport is confined to a plane by sandwiching BiFeO₃ between layers of non-polar antiferromagnetic LaFeO₃, resulting in efficient magnon transport and a higher voltage output through spin–charge conversion that can be controlled using electric fields. These results have implications for electric-field-controlled spin-based memory and logic elements.

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 evolution of cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Here, the authors employ multi-omics and multi-scale analyses to explore the genetic evolution of keratinocytes to cSCC, finding key pathogenic mutations that break the resistance to ultraviolet radiation as well as spatial heterogeneity patterns.

Isotopic labeling of organic compounds is crucial for advancements in life sciences and is extensively utilized in drug discovery. Here, the authors report the development of an in situ prepared catalyst for hydrogen isotope exchange reactions with deuterium or tritium gas as the isotope source to selectively label peptides in aqueous solutions.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Oncolytic viruses, including Zika virus, have been proposed as therapeutic option for glioblastoma (GBM) treatment, however, efficacy in patients remains suboptimal. Here, the authors show that expanding peripheral T cells with long-acting IL7 prior to intratumoral oncolytic treatment improves survival in GBM preclinical models.

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.

Generating organized kidney tissues from human pluripotent stem cell is a major challenge. Here, Freedman et al. describe a differentiation system forming spheroids and tubular structures, characteristic of these kidney structures, and using CRISPR/Cas9, delete PKD1/2, to model polycystic kidney disease.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

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.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

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 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.

Intravital imaging reveals macrophage-driven de novo induction of cancer stem cells in vivo, and their dramatic enrichment on dissemination through TMEM doorways. These findings provide a mechanism for the validated ability of TMEM doorway density to be prognostic for distant recurrence of metastatic tumors in breast cancer patients.

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

B7x is a B7-family ligand with suppressive effects on effector T cells. Here the authors show that tumor-expressed B7x promotes the conversion of conventional CD4+ T cells into regulatory T cells within the tumor microenvironment to promote immune evasion and resistance to anti-CTLA-4 therapy.

Sivanandan, Leitmann, and colleagues present the CellPaint-POSH platform, which combines pooled CRISPR screening with Cell Painting. Using self-supervised deep learning on cell images, the method enables discovery of gene function and biological networks.

The role of long non-coding RNAs (lncRNAs) in metastatic colorectal cancer (mCRC) and treatment resistance is unclear. Here, the authors use transcriptome sequencing of matched normal, primary, and metastatic CRC tissues to discover and validate that lncRNA RAMS11 promotes metastasis and resistance to topoisomerase inhibitors in mCRC.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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.

Embedding non-porous MXene film into metal thin films can achieve unprecedented shielding performance, which can be used to protect electronic components and equipment from electromagnetic noise.

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.

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.