Search

In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The influence of pregnancy on Long COVID is not well understood. Here, the authors use electronic health record data from the United States to compare the incidence of Long COVID in females after infection in pregnancy with matched non-pregnant females of reproductive age.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

High-resolution imaging and biochemical approaches provide insights into the structural and functional changes in the host cell nucleolus upon canine parvovirus infection.

Kuilman et al. established a functional genetic screening platform for the efficient identification of tumor-specific TCRs. It is compatible with routine diagnostic tumor biopsies and can be applied in fully individualized TCR-T cell therapy.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

In a phase 1b trial in three patients with Fanconi anemia, an irradiation- and busulfan-free conditioning regimen containing an anti-CD117 antibody, combined with T cell- and B cell-depleted haploidentical hematopoietic stem cell transplantation, was safe and led to high levels of donor engraftment.

Questions have arisen as to whether patients with severe COVID-19 disease can generate a T cell response against SARS-CoV-2. Tao Dong and colleagues report that convalescent patients with COVID-19 harbor functional memory CD4⁺ and CD8⁺ T cells that recognize multiple epitopes that span the viral proteome. CD4⁺ T cells predominated the memory response in patients with severe disease, whereas higher proportions of CD8⁺ T cells were found in patients with mild disease.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Linking transcription factors with disease loci implicates EBNA2, encoded by Epstein–Barr virus, in autoimmune diseases. Applying the method more widely identifies associations for hundreds of transcription factors, illuminating disease mechanisms.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

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 success of hematopoietic cell transplants is predicted by profiling minor histocompatibility antigens.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Single-cell RNA sequencing and T cell receptor sequencing are combined to identify transcriptional programs specific to mutation-associated neoantigen-specific T cells in non-small cell lung cancers treated with anti-PD-1, providing insights into resistance to PD-1 blockade.

The human colony-stimulating factor (hCSF-1) cytokine is essential for innate and adaptive immune responses. The Epstein-Barr virus protein BARF1 binds to hCSF-1, preventing interferon-α secretion. Structural and functional data reveal a new mechanism for the antagonism of human but not mouse CSF-1 signaling by BARF1.

The covid pandemic has highlighted the need for rapid antibody development. Here, authors develop an approach called SLISY, which uses NGS with phage display to simultaneously assess millions of clones to rapidly isolate specific antibodies against SARS-CoV-2 and its evolving variants.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Richard Houlston, Matthias Simon and colleagues report that common variation at 10p12.31 influences meningioma susceptibility. The risk variants are located upstream of MLLT10, which encodes an activator of Wnt-dependent transcription.

Lymphocyte function is regulated by phosphatidylinositol-dependent pathways. Uzel and colleagues identify a cohort of immunodeficient patients with hyperactive phosphatidylinositol-3-OH kinase activity due to mutant p110δ subunits, which results in enhanced senescence of cells of the immune system.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Single-cell transcriptomics excel in cell subset classification and can be augmented by suitable genotype information. Here the authors devise a long-read sequencing workflow, termed nanoranger, for detection of molecular barcodes from single-cell cDNA and apply this to clonal tracking of acute myeloid leukemia and identification of complex immune phenotypes.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Smith and colleagues find that a multivariate signature of unresolved inflammation and altered iron homeostasis detected beyond 2 weeks following acute COVID-19 onset was the strongest early differentiator of those who report long COVID symptoms at 3–10 months.

Most human herpesviruses are neurotropic and have the capability to cause serious acute and chronic neurological diseases of the nervous system. In this article, Gilden et al. review current knowledge regarding the clinical features, pathogenesis and treatment of the various neurological complications that can result from herpesvirus infections.

Primary effusion lymphoma (PEL) has a very poor prognosis. Here, the authors perform H3K27ac HiChIP in PEL cells and generate the PEL enhancer connectome, linking enhancers and promoters in PEL, as well as super-enhancers to dependency factors.

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.

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a non-Hodgkin-type B cell lymphoma. Here, the authors identify two risk loci for WM/LPL in a two-stage GWAS involving a family-oversampling approach and provide evidence for a functional role of the non-coding SNP rs116446171.

The authors use single-cell profiling and T cell receptor specificity screening to show how tumour antigen recognition shapes the phenotypes of CD8⁺ T cells and antitumour immune responses.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.