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Basal cell carcinoma is a common skin lesion and the risk loci for this cancer are beginning to be understood. In this study, the authors conduct a two-stage genome-wide association study and confirm known risk loci and identify an additional 14 loci.

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.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

A bedside-to-bench analysis identifies single-chain variable fragment linker length as an important component of chimeric antigen receptor (CAR) structure and suggests that, in contrast to CD28-based CAR T cells, tonic signaling can be beneficial for 4-1BB-based CAR T cell function.

The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia.

A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.

TDP-43 controls an exon splicing event in UNC13A that results in the inclusion of a cryptic exon associated with frontotemporal dementia and amyotrophic lateral sclerosis.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

The Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types; these data were compared with those from human to confirm substantial conservation in the newly annotated potential functional sequences and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

Histologically, PAX3-FOXO1 (P3F) fusion-positive rhabdomyosarcoma (FP-RMS) resembles muscles cells, however, its cell-of-origin is less clear. Here, the authors demonstrate that P3F expression induces endothelial cells reprogramming into functional myogenic stem cells, driving the formation of FP-RMS in mouse models.

A combination of genetic strategies and tools is used to define and fate-map different subtypes of glutamatergic pyramidal neurons according to their developmental and molecular programs, providing insight into the assembly of cortical processing networks.

Interferon (IFN) is an important component of antiviral immunity, but can also be exploited by bacteria for immune evasion. Here the authors show that Listeria monocytogenes (Lm) induces type I IFN to suppress the degradation of Lm virulence proteins, ActA and LLO, and promote Lm infection in an IFITM3-dependent manner, thereby hinting at a potential target for antimicrobial therapy.

Elevated hepatic alanine catabolism is shown to promote hyperglycaemia and reduce skeletal muscle protein synthesis, thereby linking sarcopenia with hyperglycaemia in the context of type 2 diabetes.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Interactions among spinal dorsal horn neurons and microglia contribute to the induction and maintenance of neuropathic pain after peripheral nerve injury. The authors show that depletion of macrophages in the dorsal root ganglia prevents and reverses ongoing nerve injury-induced hypersensitivity.

Malaria on Bioko Island has been reduced substantially but many acquire malaria while traveling. Here, the authors use survey data, geostatistical and mathematical modeling to investigate malaria prevalence and mobility patterns and find that in some parts of the island a significant fraction of prevalence is attributable to malaria acquired while traveling.

Single cell RNA sequencing generates short reads from one end of a template, providing incomplete transcript coverage and limiting identification of diverse sequences such as antigen receptors. Here the authors combine long read nanopore sequencing with short read profiling of barcoded libraries to generate full-length antigen receptor sequences.

Nacarelli et al. show that the nicotinamide-phosphoribosyltransferase-regulated NAD⁺ biogenesis pathway promotes the proinflammatory senescence-associated secretory phenotype by enhancing glycolysis and mitochondrial respiration during senescence.

The transcription factor TOX is a central regulator of the transcriptional and epigenetic development of exhausted T cells.

Adeno-associated viruses (AAVs) can be targeted in a tissue-specific manner, but their tissue accumulation cannot be assessed in a non-invasive manner. Here the authors conjugate a multivalent chelator labelled with Cu-64 to the surface of AAVs and image the brain accumulation of the PHB.eB capsid by PET.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.

The IFITM3 innate immunity protein directly binds presenilin near the active site and upregulates γ-secretase activity and the production of amyloid-β, and IFITM3 is upregulated in patients with late-onset Alzheimer’s disease.

NOD-like receptor family pyrin domain-containing 6 (NLRP6) reduces colitis severity in a gut microbiome-dependent manner; however, in the context of murine intestinal graft-versus-host disease, NLRP6 exacerbates symptoms independently of gut microbiome composition and diversity, with NLRP6-deficient animals displaying protection against disease.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

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.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

The mechanisms of tumor heterogeneity in pediatric hepatoblastoma remain poorly characterized. Here, the authors perform single cell RNA sequencing and identify 5 signatures with distinct responses to chemotherapy using patient-derived hepatoblastoma spheroid cultures.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Behavioural and genetic experiments in mice reveal gut-to-brain circuits driving the development of fat preference, one responding to intestinal sugar and fat using cholecystokinin signalling, and the other responding only to fat.

Matthew Meyerson, Ramaswamy Govindan and colleagues examine the exome sequences and copy number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumors. They identify novel significantly mutated genes and amplification peaks and find that around half of the tumors have at least five predicted neoepitopes.

Gallo and his colleagues report that commensal bacteria on the skin help to dampen inflammation caused by skin injury in mice. They show that, after wounding, necrotic cells release RNA that triggers TLR3 on keratinocytes, causing inflammatory cytokine release. Commensal bacteria in the skin suppress this inflammatory response through triggering TLR2 on the keratinocytes.

Irradiation to condition hosts for bone marrow transplantation leads to alterations in intestinal microbiota. Reddy and colleagues demonstrate that these changes result in reduced butyrate production and breakdown of intestinal barrier function.

Mark McCarthy and colleagues identify twelve new risk loci for type 2 diabetes through a large-scale genome-wide association and replication study in individuals of European ancestry. The identified loci affect both beta-cell function and insulin action and are enriched for genes involved in cell cycle regulation.

The use of anammox microbiomes to treat wastewater is an escalating biotechnology, yet the functional role heterotrophic bacteria play in these systems remains poorly understood. Here, Lawsonet al. use metagenomics and metatranscriptomics to reveal that heterotrophs degrade free peptides, while recycling nitrate to nitrite.

Cutaneous squamous cell carcinoma is the second most common type of skin cancer. In this genome-wide association study, which includes over 7,000 cases, the authors identify 4 new susceptibility loci for this cancer and also provide independent replication of 9 previously reported susceptibility loci.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

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.

Bitler et al. show that HDAC6 activity is essential for the survival of ovarian cancer cells carrying loss-of-function ARID1A mutation, thus representing a promising therapeutic target.