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High-fidelity reads improve variant detection and genome assembly on the PacBio platform.

Genomic deletions in poxviruses are not well understood, the authors found large deletions in >2% of Mpox virus genomes during routine surveillance, highlighting their role in poxvirus evolution and potential impact on diagnostics and therapeutics.

The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

The endoplasmic-reticulum (ER) transmembrane protein IRE1 mitigates ER stress through kinase-ribonuclease and scaffolding activities. However, a significant nonenzymatic IRE1 dependency has been shown in cancer. Here, the authors design a proteolysis-targeting chimera (PROTAC) to fully disrupt cellular IRE1 protein, selectively blocking growth of IRE1-dependent cancer cells.

Adjuvants are an important component of modern vaccines. Here, the authors employ a phenotypic screen of ~200k compounds and identify PVP-057, a TLR3 agonist with a simple scalable 3-step synthesis, as an adjuvant that induces durable humoral and cellular immunity to varicella-zoster virus (VZV) gE in mice.

A microfluidics approach that links short sequence reads enables haplotype construction and complex variation identification from tiny amounts of input DNA.

Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

Albumin selectively inhibits Mucorales growth through the release of bound free fatty acids.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

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.

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.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

cfDNA fragmentomics is a potential clinically applicable method for identifying cancer. Here, the authors assess fragmentomics analysis methods and their application to commercial targeted sequencing panels.

This study uncovers a mechanism for innate immune memory in neurons, demonstrated by a more silent epigenetic structure of the Herpes Simplex Virus genome, resulting in a deep form of latent infection that is restricted for reactivation of the virus.

Current polygenic risk scores for prostate cancer do not leverage biological mechanisms and remain inadequate for patients with African ancestry. Here, the authors employ a deep learning model to identify 2,407 non-coding polymorphisms with greater frequency in African American individuals that may affect enhancer activity in prostate cancer-related pathways, leading to more accurate polygenic risk scores.

The standardization of clinical sequencing data generation and analysis is of critical importance. Here, the authors develop the Genome Comparison and Analytic Testing platform to facilitate the development of performance metrics and comparisons of analysis tools for clinical sequencing studies.

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

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

The reconstitution of complex biological processes in cell-free systems can support the detailed characterisation of biochemical mechanisms which are difficult to probe in vivo. Here authors present an all-cell-free T7 phage cycle, consisting of cell-sized liposomes encapsulating a cell-free gene expression reaction and a phage receptor at the membrane.

Interleukin (IL)-1β has been shown to promote tumour growth in non-small cell lung cancer (NSCLC). Here the authors show using chemo-immunotherapy resistant mouse tumour models that IL-1β improves CD8 T cell recruitment in a CXCL10-dependent manner and IL-1β therapy could be a useful adjunct to chemotherapy and anti-PD-1.

Excised signal circles are circular DNA by-products of V(D)J recombination that form a complex with the V(D)J recombinase, and when increased in abundance, result in increased mutagenesis, causing adverse outcomes in cancer.

Determining the appropriate sample size (N) for bulk RNA sequencing experiments is critical to ensure reliable results. Here the authors perform an unusually large N experiment (N = 30 per group), analyzing changes in gene expression in two genetically modified mice compared to controls. They find that a surprisingly high N is required to keep the false positive rate below 50% and detection sensitivity above 50%.

Brown et al. show that mouse islet progenitors with different transcriptomes produce distinct β-cell subtypes and maternal diet alter the subtype proportions. Similar β-cell subsets exist in humans, with a subset enriched in genes related to β cell function reduced in diabetes.

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.

Metagenomes from prairie soils in Kansas, USA, show how historical exposure to water stress impacts soil microorganisms and subsequently drought responses in plants.

Here the authors use a range of approaches to examine the interplay between genetic variants linked to risk for polygenic skin diseases and transcription factors (TFs) important for skin homeostasis. The findings implicate dysregulated binding of specific TF families in risk for diverse skin diseases.

TIRTL-seq is a high-throughput method for paired T cell receptor sequencing at the cohort scale.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

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.

The authors study a disordered β-Ta film, finding that quasiparticle recombination is governed by the phonon scattering time, which is faster than conventional recombination in ordered superconductors. The authors interpret the results in terms of quasiparticle localization, which helps to understand the quasiparticle relaxation in disordered superconducting circuits.

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).

Advancements in sequencing technologies and assemblers have enabled us to generate a complete, haplotype-resolved X chromosome in cattle. This study discovers the cattle X centromere is a natural neocentromere and characterises its genetic and epigenetic structure.

Dormant liver stages of Plasmodium vivax complicate malaria elimination efforts by causing relapses that obscure the efficacy of antimalarial treatments. Here, the authors develop a high-throughput amplicon sequencing assay to reconstruct P. vivax lineages, demonstrating its capacity for geospatial infection tracking, and distinguishing recurrent malaria caused by new infections versus untreated dormant liver stages.

Chronic Kidney Disease affects 1 in 10 people worldwide with prevalence continuing to rise, thus there is a need to identify novel biomarkers that can add value to existing clinical and biochemical risk predictors. Here the authors identify miR190a-5p as potential indicator of kidney health and disease progression in patients with chronic kidney disease.

Sequence depth and read length determine the quality of genome assembly. Here, the authors leverage a set of PacBio reads to develop guidelines for sequencing and assembly of complex plant genomes in order to allocate finite resources using maize as an example.

Here, the authors demonstrate that intense laser pulses drive electrons across the full Brillouin zone in monolayer WS₂, producing quantum interferences that control high harmonic generation.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

Qu, Razmara et al. show that Gli1+ fetal cells give rise to long-lived cartilage progenitors in the long bones. While normally dormant until postnatally, they expand upon (and compensate for) growth perturbations, arising from external Pdgfra+ cells.

Genetic models for psychiatric disorders often overlook ancestry diversity. Here, the authors use PsychENCODE and GWAS data to build ancestry-specific GReX models, improving TWAS and revealing novel genes and pathways linked to brain development and psychiatric risk.

Single-cell transcriptomic analyses of Plasmodium falciparum and Anopheles gambiae reveal key developmental stages, processes and factors in parasite–mosquito interactions and identify potential targets for blocking malaria transmission.

Hepatocyte organoids derived directly from human tissue enable long-term hepatocyte expansion and can be combined with portal mesenchyme and cholangiocyte organoids to form a donor-specific periportal liver assembloid system.

This study shows that, by age 4, children understand lexical causatives to refer to direct causes and periphrastic causatives to indirect causes in causal chains. Understanding causation by absence develops later in older children.

Mutations in GJB2 cause DFNB1, the most common hereditary deafness. ATAC-seq identification of gene regulatory elements enables targeted GJB2 delivery to cochlear cells, preventing hearing loss in mouse models.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Information on immune receptor repertoire provides important insights on disease progression and therapy development, but can be expensive and time-consuming to obtain. Here the authors report ImReP, a computational method that can extract detailed immune repertoire information from existing tissue-specific RNA sequencing data.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Neuroinflammation is understudied in Parkinson’s disease (PD). Ma et al. found that clonally expanded CD8 + T cells accumulate in the brains of PD patients and interact with specific astrocytic support cells, which may fuel harmful neuroinflammation.