Search

The latest in a series of genome sequences has been published - that of the fruitfly,Drosophila. The ‘substantially complete’ sequence reveals new information about the geneticist’s favourite organism. For example, the fruitfly appears to have only half as many genes as the plant Arabidopsis thaliana, despite being anatomically more complex.

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.

An analysis of rare disease cohorts from the UK, the USA, Italy and the Netherlands identifies a neurodevelopmental disorder caused by biallelic variants in RNU2-2. Individuals with this disorder have substantially reduced levels of U2-2 small nuclear RNA in blood.

A cavity-array microscope is realized using intra-cavity lenses to create a two-dimensional array of over 40 modes, each coupled to a single atom in free-space.

Islands and mountaintops are often considered evolutionary dead ends. Using whole genomic data of 18 bird species and demographic models, the authors show that populations become isolated at high elevations, but disjunct montane populations maintain gene flow and thus the capacity for further colonisation.

The authors estimate genomic vulnerability for closely related species of rainbowfish. They find that narrow endemic species that have hybridized with a warm-adapted generalist show reduced vulnerability to climate change and that hybridization may facilitate evolutionary rescue for such species.

Catabolism of extracellular glutathione by γ-glutamyltransferases supports tumour growth and survival, and pharmacological targeting of these enzymes slows tumour growth.

The mammalian gut undergoes a dramatic transformation during mid-gestation to create intestinal villi. Zhu and colleagues show that the transcription factor Foxl1 impacts key events during the epithelial transition of the fetal mammalian gut.

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.

New York City is one of the areas most affected by the SARS-CoV-2 pandemic in the United States, and there has been large variation in rates of hospitalisation and death by city borough. Here, the authors show that boroughs with the largest reduction in daily commutes also had the lowest SARS-CoV-2 prevalence.

Berg et al. identify that primary cilia regulate early valve development in mouse embryos by participating in cushion development, where they function as mechanosensors regulating endothelial-to-mesenchymal transition through the modulation of Klf4.

Stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads using a two-vector system of enveloped delivery vehicles and adeno-associated viruses.

Lupu, Grainger, Kirschnick et al. show that, contrary to prevailing belief, the initial specification of mammalian lymphatic endothelial cells primarily occurs from previously unidentified mesenchymal angioblasts rather than from venous endothelium.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Using two-photon intravital imaging, the authors show that mechanical stress in skin triggers fluid-filled “stress vesicles” in epidermal cells, altering Piezo1-dependent calcium signals to drive stem cell differentiation and protect tissue integrity.

Erlich et al. show that soluble LTα and membrane-bound LTα1β2 lymphotoxins expressed by B cells play distinct roles to attenuate the pathology observed in ileitis.

In one-shot perceptual learning, what we see can be dramatically altered by a single past experience. Using psychophysics, fMRI, iEEG, and DNNs, the authors identify neural and computational mechanisms underlying this remarkable ability in humans.

Crystalline materials for optical applications are synthesized in living dinoflagellates.

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 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.

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.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

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.

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.

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.

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.

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.

How cellular metabolism influences tissue-resident macrophage survival is currently unknown. The authors here demonstrate that SerpinB2 regulates mitochondrial function to promote tissue-resident macrophage survival.

The central nervous system undergoes constant immune surveillance, but the route that immune cells take to exit the brain has been unclear as it had been thought to lack a classical lymphatic drainage system; here functional lymphatic vessels able to carry both fluid and immune cells from the cerebrospinal fluid are shown to be located in the brain meninges.

Pampols-Perez et al. identify the mechanosensitive ion channel PIEZO2 as a novel marker for embryonic coronary artery endothelial cells and as a critical regulator of coronary vascular remodeling. They show that in a distinct subset of coronary endothelial cells, PIEZO2 translates mechanically activated ionic currents into biological signals guiding coronary artery morphogenesis.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline. Here the authors describe an epigenome-wide association study (EWAS) of human post-mortem brain samples across multiple independent AD cohorts. They find consistent hypermethylation of the ANK1 gene associated with neuropathology.

Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.

Galsky and colleagues report the results of a phase 1 clinical trial of anti-programmed cell death protein 1 ligand 1 atezolizumab in combination with PGV001, a personalized neoantigen vaccine, in participants with urothelial cancer.

The Mid-Cayman Spreading Centre is an ultraslow-spreading mid-ocean ridge in the Caribbean. This study reveals two hydrothermal vent fields on the ridge, including high-temperature vents on an off-axis oceanic core complex where, similar to Mid-Atlantic vents, an alvinocaridid shrimp is common at both vent fields.

The authors identify key enzymes, including four cytochrome P450s, a dehydrogenase and a sulfotransferase, that together build the core chemical scaffold of withanolides, medicinal compounds from ashwagandha with neurological and anti-cancer activities.

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.

Here the authors perform longitudinal sampling of lymphoid organs along with fate mapping and matched single-cell RNA sequencing and TCR sequencing to define the developmental dynamics of follicular regulatory T (T_FR) cells. They find that T_FR cells undergo clonal expansion and progressive differentiation in a process that requires follicular helper T cells.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.