Search

Phage–host interactions are computationally predicted using only genomic information, highlighting future research directions and enabling generation of custom phage cocktails.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The authors show that increased Xist RNA levels can induce de novo silencing of genes that normally escape X inactivation. SPEN depletion prevents the silencing of escape genes upon Xist RNA overexpression in neural progenitors.

Structural variations (SV) contribute to inter-individual variability. Here, the authors describe a first-generation multi-ancestry Asian SV catalogue containing 73,035 SVs from 8392 Singaporeans to provide insights into Asian SV diversity.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Carty et al. identify the H3K9 methyltransferases that restrict the size and position of the centromere protein A chromatin domain, maintaining functional centromeres.

A previously unsampled deep lineage in central Argentina was discovered that had distinctive genetic drift by 8,500 bp and persisted as the main Native American ancestry component in the region up to the present day.

A six-letter sequencing workflow can simultaneously detect genetic and epigenetic bases.

Oaks can live hundreds of years. Comparative genomics using a high-quality genome sequence provides new insights that may explain tree longevity. Samples from branches and corresponding acorns also help quantify heritable somatic mutations.

Extrachromosomal DNA makes cancerous tumours resistant to treatment, but this research demonstrates that increasing transcription–replication conflict allows for targeted elimination of cancer cells containing extrachromosomal DNA, and thus sustained tumour regression in mice.

This study analysed genetic data of soil-transmitted helminths from 27 countries, revealing diversity impacting molecular test accuracy and highlighting the need to adapt diagnostics for effective STH surveillance.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Barbera et al. identify and map genetic variants that alter the characteristics of vascular smooth muscle cells and contribute to the risk of coronary artery disease.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours. Here the authors report that BCA and BCAC patients possess distinct genomic profiles despite histopathological similarities, and identify a recurrent FBXW11 missense mutation (p.F517S) which leads to accumulation of β-catenin in BCA and higher expression of Wnt/β-catenin targets.

Many populations suffer from negative fitness effects of inbreeding, but the genetic mechanism is not well known. Here the authors study an arctic fox population and find that expression of strongly harmful mutations lowers reproduction and longevity, whereas moderately harmful ones lower survival.

In the randomized phase 1b/2 Morpheus-Melanoma trial evaluating various neoadjuvant immune checkpoint inhibitor regimens in patients with resectable stage III melanoma, tobemstomig, an anti-PD-1/anti-LAG-3 bispecific antibody, showed the highest pathologic response rate with a better safety profile than the standard treatment approach of ipilimumab plus nivolumab.

Comparison of paired primary and recurrent glioblastomas at the single-cell transcriptomic level describes molecular and cellular trajectories associated with tumor recurrence, highlighting extensive heterogeneity and microenvironmental co-evolution.

Integrated single-cell transcriptomic and genetic characterization of 121 adult glioblastomas identifies heterogeneity at cell type, cell state and baseline expression program levels associated with specific mutations that form three stereotypical ecosystems.

A study of myeloid cells in gliomas, a type of brain tumour, used a factor-based computational framework to reveal four immunomodulatory gene-expression programs that are expressed across myeloid cell types, driven by microenvironmental cues and predictive of therapeutic response.

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.

Asexual vertebrates are extremely rare. Here, the authors sequence the genome of the Amazon molly, an asexual fish, and find few signs of genetic degeneration but clonal polymorphism and high heterozygosity, which might explain the success of this species.

Here the authors reveal that a strong bottleneck and slow growth of ancestral effective population size in Papua New Guinean populations can be mistaken for admixture with an earlier out-of-Africa population.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Blockade of the C5a–C5aR1 axis using anti-C5aR1 monoclonal antibodies prevented inflammation associated with COVID-19.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

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

Single-nucleus ATAC-seq characterization of chromatin accessibility in human coronary artery disease samples identifies cell-type- and state-specific regulatory mechanisms underlying disease risk, highlighting the roles of TBX2 and PRDM16.

Chemical profiling in hyponeddylated cells coupled with multi-omics target deconvolution led to the identification of molecular glue degraders of cyclin K that function by inducing proximity between the CRL adaptor DDB1 and a CDK12–cyclin K complex.

During meiotic recombination, genetic information is transferred or exchanged between parental chromosome copies. Using a large hybrid mouse pedigree, the authors generated high-resolution maps of these transfer/exchange events and discovered new properties governing their processing and resolution.

The understanding of pathogenicity in quantitative plant pathosystems remains limited. This study reveals the genetic architecture of quantitative pathogenicity traits in a significant fungal plant pathogen, shedding light on potential evolutionary mechanisms involved in host adaptation.

Galectin-3 (Gal-3) has been proposed to have a pathogenic role in systemic sclerosis (SSc). Here, the authors identify a Gal-3-based transcriptomic signature associated with SSc severity in patients and demonstrate that Gal-3 blockade reduces the severity of SSc skin and lung lesions in murine models.

Stepwise evolution of invasive Salmonella Typhimurium in Africa is defined using genotypic and phenotypic analyses of isolates collected over a 50-yr period.

Nicolas Dussex et al. identify a 44,000–49,000 year old bird found in Siberian permafrost as a female horned lark using ancient DNA. This exceptionally well-preserved specimen illustrates the potential contribution to science of permafrost deposits, such as the study of ecology and evolution of ancient ecosystems, calibration of molecular clocks, and furthering our understanding of processes such as biological regulation and gene expression in relation to climate change.

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).

The role of Africa in the global spread of highly pathogenic avian influenza (HPAI) is not well understood. Here, using evolutionary analyses, the authors show that Africa mainly acts as ecological sink for HPAI H5, and reveal varying paths of HPAI incursions either through domestic or wild birds.

In Drosophila, the Calypso–ASX complex catalyzes H2A deubiquitination and aids Polycomb in transcriptional silencing. Here the authors show that the orthologous complex, BAP1.com, promotes gene activation by counteracting PRC1-mediated gene silencing.

The role of histone mutations in leukemogenesis remains largely unexplored. In this study of AML, the authors show that histone mutations are early events that drive a more aggressive phenotype.

Netrin-1, via precise Neo1/Unc5B stoichiometry, promotes naive pluripotency, embryonic stem cell self-renewal in combination with leukaemia inhibitory factor, and the formation of the mouse epiblast in vivo.

Uveal melanoma has a propensity to metastasise. Here, the authors report the whole genome sequence of 103 uveal melanomas and find that the tumour mutational burden is variable and that two subsets of tumours are characterised by MBD4 mutations and a UV exposure signature.

Mutational signatures in melanoma are associated with prognostic features in patients and suggest distinct disease etiologies associated with the influence of different wavelengths of ultraviolet radiation.

Repeated evolution provides valuable insight into adaptation. In this study, the authors found that repeated evolution of cave-adapted phenotypes of a fish (Astyanax mexicanus) was driven by selection on standing genetic variation and novel mutations and genes repeatedly under selection are longer compared to the rest of the genome.

This study reports that nuclear speckle constituents have two expression states in cancer correlating with patient survival and HIF-2α functional programs. HIF-2α mediates nuclear speckle association of key genes activated in renal cancer.

Hereditary tyrosinemia type 1 (HT1) is an inborn error of metabolism caused by a deficiency in fumarylacetoacetate hydrolase (FAH). Here, the authors show in an animal model that HT1 can be treated via in vivo portal vein administration of a lentiviral vector carrying the human FAH transgene.

Netrin-1 is upregulated in cancer models that undergo spontaneous epithelial-to-mesenchymal transition, and its targeting blocks the progression of tumour cells to a late mesenchymal state, suggesting possible therapeutic applications.

Here the authors describe that the human origin recognition complex subunit 1 (ORC1) binds to RNAs transcribed from genes with origins of replication at their TSS impacting origin activation.

The transcriptional adaptation processes of harmful self-reactive CD8+ T cells in the central nervous system are not well understood. Here the authors use a system in which self-reactive and virally generated CD8+ T cells are directly compared in vivo and demonstrate that TOX expression contributes to maintenance of auto-reactive CD8+ T cells through alteration of chromatin accessibility.

The transcription factor ThPOK is critical for homeostasis and differentiation of mature helper T cells. Here, Kappes and colleagues describe a ThPOK-mediated positive autoregulatory loop that is crucial for tissue-specific T_reg cell differentiation, maintenance of intestinal T_reg cell integrity and conversion of these cells into CD4⁺ intraepithelial lymphocytes.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.