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Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Daniel, Yost, Hsiung, et al. generate a single-cell multiomic atlas of T cell exhaustion in chronic viral infection, which reveals molecular programs of exhausted T cell subsets, identifies divergent clonal exhausted T cell differentiation trajectories and nominates TCR signal strength as a driver of clonal fate.

Ernesto Guccione and colleagues report that the transcription factor PRDM15 regulates naive pluripotency in mouse embryos and embryonic stem cells and in derivation of mouse and human iPSCs. They further show that PRDM15 promotes WNT signaling and inhibits MAPK–ERK signaling by directly regulating the expression of R-spondin1 and Sprouty1, respectively.

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.

Tracing the source of malarial infections is an important step towards monitoring and controlling the disease. Here, Preston et al. analyse sequence data from 711 isolates and design a genetic barcode based on combined mitochondrial and apicoplast genomes that is able to distinguish between malaria parasites isolated from different geographical regions.

Lymphotoxin regulates lymphoid organ architecture and adhesion molecules involved in lymphocyte trafficking. Here the authors show that lymphotoxin produced by regulatory T cells promotes their migration to the draining lymph nodes by engaging its cognate receptor on lymphatic endothelial cells.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Martin Farrall and colleagues report the results of a large genome-wide association meta-analysis of coronary artery disease based on 1000 Genomes imputation. They identify ten new risk loci and show that susceptibility to this disease is largely determined by common SNPs with small effect sizes.

A microfluidic assay predicts the metastatic potential of breast cancer specimens by quantifying the abundance and proliferative index of the migratory cells within them.

Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

SDH inactivation is associated with cancer susceptibility. Cardaci et al. report a metabolic vulnerability in SDH-deficient cells, by showing that they depend on pyruvate carboxylation for the production of aspartate, proliferation and tumour growth.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

Analysis of the hydrolysis kinetics of strigolactone receptors using enzyme-activated fluorescent probes revealed that the catalytic triad histidine of the receptor forms a covalent interaction with the strigolactone hydrolysis product, the D ring.

A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

In an effort by several research groups, a genome-wide RNAi-based screen presents a list of validated genes involved in cilia assembly and maintenance, and reveals previously unidentified ciliopathy factors.

The nuclear A-type and B-type lamins, key components of the lamina underlying the nuclear envelope, have been linked to the regulation of several nuclear processes. However, studies in mice have questioned the essentiality of these lamins and have provided new understanding of how lamins function in different cells and tissues.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

Analysis of changes in functional groups of species and potential drivers of environmental change for protected areas across the world’s major tropical regions reveals large variation between reserves that have been effective and those experiencing an erosion of biodiversity, and shows that environmental changes immediately outside reserves are nearly as important as those inside in determining their ecological fate.

Glycosylation refers to the addition of carbohydrate chains to proteins and lipids. In this Review, the authors discuss the broad role of glycans in immunity, cancer, xenotransplantation and glomerular filtration and the potential of ‘glycomedicine’.