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Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

Urbanization disrupts oak tree microbiomes by reducing beneficial fungi and increasing plant and human pathogens across leaves, roots and soils, with consequences for tree health, urban climate mitigation and potential human exposure to pathogens.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

Analysis of human Robertsonian chromosomes originating from 13, 14 and 21 reveal that they result from breaks at the SST1 macrosatellite DNA array and recombination between homologous sequences surrounding SST1.

Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ₁ modify the same host tRNA. PreQ₁-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Using MPXV genomes specific to New York City, phylogenetic clusters were identified. Most mutations were driven by ABOBEC3. The prevalence of coinfections with distinct strains was ~4.2% and results may improve MPXV genomic epidemiology applications.

The authors in this work identify an in vivo CNS active bifunctional degrader of GSK3. This was discovered via development of orthogonally reactive linker chemistry and a direct-to-biology screen that was able to provide hits of in vivo chemical probe quality.

The authors identify defective viral particles, in people with non-suppressible HIV-1, that can replicate through superinfection and interfere with the wild-type virus. However, they show no evidence of these preventing disease progression in the individuals studied.

Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

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.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

A report from the first 2,000 newborns enrolled in the Early Check program, which offered genome screening covering 198 genes associated with early-onset diseases, shows the feasibility and potential clinical utility of the approach, leading to 28 true positive results.

Genome-wide approaches have uncovered the vast microbial and viral diversity across ecosystems. This Review explores advances in metagenomics, single-cell sequencing and functional profiling to elucidate the evolution, biogeography and ecological dynamics of Earth’s microbiomes.

Many autoimmune and genetic causes of sporadic late-onset cerebellar ataxia (SLOCA) can now be identified, but some individuals remain categorized as having idiopathic SLOCA. Wirth and colleagues discuss advanced genomic techniques that might identify additional ‘missing’ SLOCA causes, potential prognostic biomarkers and progress towards effective treatments.

RNA alternative splicing is involved in determining cell identity, but a comprehensive molecular map is missing. Here, the authors provide a human and mouse brain atlas of transcript isoforms linking them to cellular identity, brain regions and development stages.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Here, the authors use cryo-EM and biochemical analysis to investigate how the CRISPR-associated protein Cas9 interrogates DNA to locate its RNA-matching target sequence.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus.

The broad activity windows of current base editors pose a major challenge to their therapeutic application. Here, the authors established a generalizable re-engineering framework to narrow the activity windows of diverse base editors, streamlining the development of therapeutic base editing.

Li et al. discovered that the cytotoxic synthetic small molecule BRD1732 is directly ubiquitinated in cells. Ubiquitination of BRD1732 is E3 ligase dependent and leads to inhibition of proteasomal degradation.

Analysis of 170 human genomes assembled using long-read sequencing provides a map of structural variation within regions of segmental duplication and identifies novel candidate protein-coding genes supported by full-length Iso-Seq reads.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

RNA-guided CRISPR-associated transposases (CAST) are natural systems with broad potential in biotechnology. Here, the authors report compact type V-K CAST discovered from genome-resolved metagenomics and demonstrate targeted integration of a large transgene to a safe-harbor site in the human genome.

Long non-coding RNAs are increasingly recognised to be important factors in regulating cellular processes and comprise a large faction of the transcriptome, however most are uncharacterised. Here the authors present RACE-Seq, a tool to improve and extend the annotation of low-expression transcripts.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

The study reports the cloning of paired NLR genes CNL and NL from wild emmer wheat and demonstrates their coordinated function in conferring Yr84-mediated wheat stripe rust resistance.

Brain-machine interfaces are hindered by neuroinflammation. Here, the authors found that bacterial sequences invade the brain post-microelectrode implantation. Antibiotic-treated mice showed reduced bacterial presence and altered neuroinflammatory profile, temporarily improving recording performance.

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

CD4⁺ T cells promote immunity to tuberculosis infection via macrophages. Here the authors show upregulation of SLAMF1/CD150 on infected macrophages after interaction with CD4⁺ T cells and that the presence of SLAMF1 promotes ROS production by macrophages and the absence of Slamf1 in macrophages results in higher mycobacterial loads in infected mice.

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.

The Ly49 gene family mainly encodes inhibitory or activating surface receptors on natural killer cells. Here the authors show that in mice, inhibitory and activating Ly49 genes are regulated by two distinct sets of cis-regulatory elements, and that different Ly49 genes can be cross-regulated.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

The assembly of individual genomes from complex microbial communities is improved by sequencing of barcoded fragments.

Electrochemistry can boost processes that trap atoms inside a metal. A reactor uses these trapped atoms, combined with an ion beam, as fuel for nuclear fusion.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

RNA Capture Long Seq (CLS) is a new method for transcript annotation that combines targeted RNA capture with long-read sequencing. CLS reannotates GENCODE lncRNAs and increases the number of validated splice junctions and transcript models for targeted loci.

GROC-SVs enables the accurate detection and reconstruction of large and complex structural variants from read clouds generated by the 10x Genomics platform and subsequent Illumina sequencing.

Sequencing analyses of human prefrontal cortex from donors ranging in age from 0.4 to 104 years show that ageing correlates with an accumulation of somatic mutations in short housekeeping genes and a reduction in the expression of these genes.