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Pleiotropic loci and genome-wide genetic correlations have identified shared heritability across some types of cancers. Here, the authors perform genome-wide association studies and characterize pan-cancer heritability and pleiotropy in individuals of European ancestry across 18 cancer types from two large cohorts.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

HIV patients have an increased risk of developing non-AIDS-defining cancers but the molecular mechanisms underlying this predisposition are unclear. Here the authors show that exosomes secreted by HIV-infected T cells or isolated from the blood of HIV-positive patients, stimulate oncogenic properties of cancer cells through the activation of ERK1/2 signaling pathway.

A study of multisystem inflammatory syndrome in children (MIS-C) shows maintenance of elevated levels of monocyte-activating pathogen-specific IgG not seen in children infected with SARS-CoV-2 who do not develop MIS-C.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Michael Stratton and colleagues report a genome-wide association study for testicular germ cell tumor (TGCT) in a UK population, identifying three associated loci.

Heymut Omran, Mary Porter and colleagues identify the nexin link–dynein regulatory complex subunit DRC1 from Chlamydomonas and show that mutations in the human DRC1 homolog CCDC164 cause primary ciliary dyskinesia. Their analyses show that loss of DRC1 results in distinct axonemal defects and altered ciliary beat patterns.

Classical Hodgkin lymphoma is a cancer that originates in lymph nodes. Little is known about its genetic susceptibility. Here, the authors combined existing and new genome-wide association studies to identify risk loci for classical Hodgkin lymphoma at 6q22.33, and nodular sclerosis Hodgkin lymphoma at 3q28, 6q23.3, 10p14, 13q34, 16p13.13.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

From a new species of β-proteobacteria, an antibiotic called teixobactin that does not generate resistance has been characterized; the antibiotic has two different lipid targets in different bacterial cell wall synthesis components, which may explain why resistance was not observed.

The inhibitory receptor programmed death-1 (PD-1) is upregulated on exhausted CD8⁺ T cells in HIV-infected individuals. Quigley et al. analyzed the transcriptional profile induced by PD-1 ligation and report that a transcription factor, BATF, is upregulated by PD-1 signaling and has a key role in PD-1–mediated inhibition of T cell function.

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.

An antibody against the pituitary hormone Fsh reduces adiposity and increases thermogenesis in ovariectomized mice or mice fed a high-fat diet.

Doug Epstein and colleagues present biochemical and transgenic studies implicating Six3 in the regulation of Shh forebrain expression through direct binding to a remote enhancer. The work was driven by the discovery of a rare variant in this enhancer in an individual with holoprosencephaly

Oral-vaccine-induced IgA cross-links growing bacteria into clonal aggregates, inhibiting pathogenesis, adaption and the spread of antimicrobial resistance genes.

Initial results from phase I/II lentiviral gene therapy trials provide early evidence supporting its safety and efficacy in treating patients with X-linked chronic granulomatous disease.

Monoallelic HLA-DRB1 cell line panel with universal BCR unlocks the immunopeptidomic potential of B cells.

Using whole-transcriptome sequencing, this paper identifies recurrent gene translocations in B-cell lymphomas that involve the MHC class II transactivator CIITA. These translocations lead to downregulation of cell surface HLA class II expression and, in the case of some fusion partners, overexpression of CD274/CD273 ligands, which have the potential to reduce the antitumour response against these lymphomas.

Immune-checkpoint inhibitors are associated with a unique spectrum of organ-specific inflammatory toxicities known as immune-related adverse events (irAEs). In the past few years, aggregate clinical data, real-world data and multi-omics data have been used to investigate the underlying mechanisms and clinical presentations of irAEs. The authors of this Perspective summarize the knowledge on irAEs that has been obtained from different sources of ‘big data’.

Immune checkpoint inhibitors (ICIs) are now an established cornerstone of cancer therapeutics; however, ICIs are associated with toxicities in various organs, termed immune-related adverse events. This Review highlights current understanding in ICI-induced endocrinopathies, including epidemiology, aetiology, clinical manifestations and approaches to treatment.

Cao et al. show that human papillomavirus-positive, head and neck squamous cell carcinoma patients are associated with better survival when T-cells are activated. This study suggests that viral infection may recruit immune effector cells and that it may activate PD-1 and CTLA-4 immunosuppressive pathways.

Conspiracy theories have the potential to undermine governments, promote racism, ignite extremism and threaten public health efforts. In this Review, Hornsey et al. synthesize the literature on factors that shape conspiracy beliefs at the individual, intergroup and national level.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

It is an outstanding challenge to develop intelligent machines that can learn continually from interactions with their environment, throughout their lifetime. Kudithipudi et al. review neuronal and non-neuronal processes in organisms that address this challenge and discuss pathways to developing biologically inspired approaches for lifelong learning machines.