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Epstein–Barr virus (EBV) is a widespread herpesvirus linked to cancer and autoimmune disease. The authors in this work design and characterize a stabilized prefusion form of gB, an essential viral fusion protein, advancing EBV vaccine and therapeutic development.

Human host-associated cellular products may act as induction agents for bacteriophages.

In this phase 1 trial, treatment of patients with fibrolamellar hepatocellular carcinoma with a therapeutic peptide vaccine targeting the fusion kinase DNAJB1–PRKACA, which is the driver of the disease, together with nivolumab and ipilimumab, was safe and led to encouraging preliminary clinical responses, and translational analysis showed activation of immune responses.

Jeremy Barr discusses how he began studying bacteriophages, the historic use of the T-series phages and how they have shaped the field.

The Entelli-02 phage product containing five phages has frontline potential to address infections caused by the multidrug-resistant Enterobacter cloacae complex.

Authors profile the antimicrobial activity of an Escherichia coli bacteriophage (in vivo and in vitro), isolated from chicken faeces.

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.

Accurate prediction of immunogenic CD8⁺ T cell epitopes would greatly accelerate T cell vaccine development. A new deep learning model, MUNIS, can rapidly identify HLA-binding, immunogenic and immunodominant peptides in foreign pathogens.

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.

In this phase 1 trial, patients with heavily pretreated and refractory CD30⁺ lymphoma were safely treated with donor-cord-blood-derived NK cells that were precomplexed with the anti-CD30 and anti-CD16A bispecific antibody AFM13, showing encouraging preliminary clinical response rates.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

The genetic basis of gastric cancer, the fourth most common cancer worldwide, remains poorly understood. Here, the authors sequence and analyse the exomes and transcriptomes of primary gastric tumours and cell lines, and identify a ZAK kinase isoform that may have an oncogenic role in gastric cancer.

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.

Perro and colleagues develop a CD3⁺ T cell engager co-targeting BCMA and CD38 to improve immunotherapy for multiple myeloma, demonstrate cytotoxicity in patient-derived samples and murine models and develop a quantitative systems pharmacology model.

This study finds that glaciers have existed in the Transantarctic Mountains for the past 60 million years, and that warm-based mountain glaciers were present in Antarctica long before ice sheets came to dominate the continent.

In patients with advanced melanoma, fecal microbiota transplantation from healthy donors combined with the anti-PD-1 inhibitors nivolumab or pembrolizumab was well tolerated with an encouraging objective response rate of 65% in the first-line treatment setting.

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.

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

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

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.

Here the authors use single cell profiling of T cells across the human lifespan to show that a suboptimal TCR shift in T cells as we enter older age results in a molecular signature that resembles that of T cells from newborns and children.

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.

The authors characterize immune response in Omicron-infected vaccinated individuals and observe an immune enhancement. While increases in neutralizing antibodies and spike T cells are stronger in previously naïve individuals, mucosal antibodies and non-spike responses increase regardless of infection history.

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.

Here the authors provide the biospecimen collection methodology from the SpaceX Inspiration4 mission, including venous blood, capillary blood, saliva, urine, stool, skin biopsy, body swab, and environmental swab samples.

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.

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.

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.

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.

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.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

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.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

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.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Cross-protective responses across all strains of influenza virus (IAV, IBV and ICV) are a key goal of universal vaccines against influenza. Kedzierska and colleagues identify cytotoxic T cells present in blood and lungs of healthy people that are directed against all strains of influenza virus.

Genomics analyses reveal that in vitro culture of CAR T cells can lead to reactivation of a latent herpesvirus, which might be involved in complications in patients receiving associated cell therapies.

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

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.