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The antiviral protein SP140 negatively regulates Ifnb1 mRNA stability by directly repressing the expression of the immune regulator RESIST.

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.

Combined high-throughput protein engineering with machine learning to curate libraries of CRISPR genome-editing enzymes with distinct genome targeting properties is described.

Over 11,000 plasma and cerebrospinal fluid proteomic samples reveal that the APOE ε4 genetic variant is associated with a systemic pro-inflammatory signature in a variety of neurodegenerative diseases.

Spectra decomposes gene expression data into interpretable programs using prior knowledge.

While anti-retroviral therapy (ART) helps contain HIV, whether adoptive T cell therapy further improve the prognosis is unclear. Here the authors conduct an open-label, single-arm phase 1 study to assess the safety (primary outcome) and characteristic (secondary outcome) of autologous, HIV-specific T cell therapy to find it safe to warrant further efficacy assessment.

The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.

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.

Burkitt lymphoma (BL) is the most common pediatric B-cell lymphoma. Here, within the International Cancer Genome Consortium, the authors performed whole genome and transcriptome sequencing of 39 sporadic BL, describing the landscape of mutations, structural variants, and mutational processes that underpin this disease how alterations on different cellular levels cooperate in deregulating key pathways and complexes.

The promise of engineered T cells for treating cancer has been mitigated by their poor persistence when transferred to patients. Pule et al. now show that dual-specific T cells that recognize an Epstein-Barr virus (EBV) antigen and a tumor antigen survive longer in individuals with neuroblastoma. Engineering virus-specific T cells to recognize tumor antigens may improve the efficacy of this immunotherapy in latently infected cancer patients (pages 1148–1150).

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.

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

Although Huntington’s disease (HD) is a well-studied genetic disorder, less is known about the epigenetic changes underlying it. Here, the authors characterize DNA methylation levels in tissues from patients, a mouse huntingtin (Htt) gene knock-in model, and a transgenic HTT sheep model, and provide evidence that HD is accompanied by DNA methylation changes in these three species.

A multi-tissue atlas of alternative polyadenylation (APA) quantitative trait loci (3′aQTLs) identifies approximately 0.4 million common genetic variants associated with the APA of target genes. Approximately 16% of trait-associated variants colocalize with 3′aQTLs.

Clinical use of engineered bacteriophages for the treatment of disseminated mycobacterial infection.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Cryo-electron microscopy structures of NMDA receptors in open and apo states reveal the molecular mechanism underlying the dual ligand requirement for its channel gating and opening.

Koelle and colleagues use an activation marker-dependent approach to determine the recruitment of TCR by three doses of mRNA vaccination in individuals previously infected with SARS-CoV-2.

Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP_105–113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP_105–113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.

Gilean McVean and colleagues report the results of a large-scale clinical genome sequencing project spanning a broad spectrum of disorders. They identify factors influencing successful genetic diagnosis and highlight the challenges of interpreting findings for genetically heterogeneous disorders.

Hess and colleagues perform metabolic screens in B cells from patients with primary antibody deficiency and find that germline mutations in the succinate dehydrogenase subunit SDHA drive the expression of the cytokine IL-6 in patients with persistent polyclonal B cell lymphocytosis.

Geometry is crucial in spatial reorientation, but the underlying neural mechanisms of spatial reorientation are unclear. Here, the authors show that in a two-context reorientation task, distinct CA1 cells code heading retrieval and context recognition during reorientation.

The COVID-19 pandemic sparked the need for international collaboration in using clinical data for rapid development of diagnosis and treatment methods. But the sensitive nature of medical data requires special care and ideally potentially sensitive data would not leave the organization which collected it. Xiang Bai and colleagues present a privacy-preserving AI framework for CT-based COVID-19 diagnosis and demonstrate it on data from 23 hospitals in China and the United Kingdom.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Michael Talkowski and colleagues examine karyotypically balanced genomic rearrangement landscapes in the germline at single-nucleotide resolution. They find predominant roles for complex reorganization and non-homologous repair in such 'chromothripsis' processes, suggesting a mechanism of template switching and blunt-end ligation.

Bernhard Radlwimmer and colleagues report whole-genome bisulfite sequencing of 13 Burkitt lymphomas and nine follicular lymphomas. They find that both types of germinal center B cell lymphomas show global hypomethylation compared to normal germinal center B cell precursors and identify regions of differential methylation that correlate with somatic mutations and differential gene expression.

Phage libraries are a promising source of cell-selective peptides, but their use as gene therapy vectors remains highly speculative (pages 299–305).

When people view an object, they can often guess the setting from which it was drawn and the other objects that might be found in that setting. Here the authors identify regions of the human visual system that represent this information about which objects tend to appear together in the world.

Adaptation is thought to improve discrimination by pulling neural representations of similar stimuli farther apart. Here, the authors separately show that adaptation to a 3D shape class leads to better discrimination performance on similar shapes, and activity patterns diverge in object selective cortical areas.

Richard Houlston and colleagues report results of a genome-wide association study of Hodgkin's lymphoma. They identify three new susceptibility loci at 2p16 (REL), 8q24 and 10p14 (GATA3) and confirm a strong role for the HLA region in disease etiology.

Although head direction cells are known to encode information related to an organism's heading, it is unclear how the brain integrates this with information provided by fixed environmental features. In this study, the authors show that the retrosplenial complex is important for encoding heading and facing direction based on local landmarks and that this process generalizes across different environments that have similar geometry.

Genome-wide association studies combined with data from epigenomic maps for immune cells have been used to fine-map causal variants for 21 autoimmune diseases; disease risk tends to be linked to single nucleotide polymorphisms in cell-type-specific enhancers, often in regions adjacent to transcription factor binding motifs.