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A study of myeloid cells in gliomas, a type of brain tumour, used a factor-based computational framework to reveal four immunomodulatory gene-expression programs that are expressed across myeloid cell types, driven by microenvironmental cues and predictive of therapeutic response.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

The authors model subglacial water flow in East Antarctica and show significant drainage reorganization from 34 Mya to the present and forward to 2100 CE. These drainage networks affect ice dynamics, ice shelf melt, and resulting sea level change.

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).

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

In a single-arm phase 2 trial evaluating intravesical delivery of the oncolytic adenovirus cretostimogene grenadenorepvec with systemic anti-PD-1 in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ, the complete response rate at 12 months was 57.1%, meeting the primary endpoint.

The soil microbiome communicates with plant roots using a chemical language. Here, using p-coumaroyl-homoserine lactone as the synthetic communication signal, the authors demonstrate programmable microbe-to-plant communication from the sender in the soil bacteria to a receiver in the plant.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The collective-flow-assisted nuclear shape-imaging method images the nuclear global shape by colliding them at ultrarelativistic speeds and analysing the collective response of outgoing debris.

A new technology for proteome-scale assessment of human exoproteome–microbiome interactions exposes an extensive network of transkingdom connectivity.

Transcriptomic and chromatin accessibility analyses of naive and transplanted colon cancer organoids in a mouse model reveal a key role for the transcription factor SOX17 in establishing a permissive immune environment for tumour cells.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Nicole Soranzo and colleagues report a meta-analysis of genome-wide association datasets identifying 22 associations to 8 clinically relevant hematological traits. They also identify a long-range haplotype at 12q24 that includes variants associated with platelet counts as well as coronary artery disease and shows evidence of a selective sweep in Europeans.

An antimatter hypernucleus formed by an anti-lambda hadron, an antiproton and two antineutrons was observed through its two-body decay after production in ultrarelativistic heavy-ion collisions.

Current methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) that form metastases have several limitations. Here, the authors show an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts.

Lamin mutations responsible for muscular dystrophy are shown to reduce nuclear envelope stability, resulting in mechanically induced nuclear envelope rupture, DNA damage and activation of DNA damage response pathways that lead to muscle cell death. Preventing nuclear envelope damage by reducing cytoskeletal forces on the nucleus improves muscle fibre health and function.

Spatial transcriptomics aims to pair omic data with tissue structure. Here the authors report Spatially PhotoActivatable Colour Encoded Cell Address Tags (SPACECAT) to track and isolate live cells by ___location; this enables spatially informed downstream assays like scRNA-seq and flow cytometry.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

The African Genome Variation Project contains the whole-genome sequences of 320 individuals and dense genotypes on 1,481 individuals from sub-Saharan Africa; it enables the design and interpretation of genomic studies, with implications for finding disease loci and clues to human origins.

UDP-glucuronic acid is a component of the extracellular matrix. Here, the authors report biallelic variants in the gene encoding UDP-Glucose 6-Dehydrogenase (UGDH) in individuals affected by developmental epileptic encephalopathies that impair UGDH stability, oligomerization, or enzymatic activity in vitro.

Serum antibody responses to sequential homologous booster vaccines derive overwhelmingly from primary cohort B cells at the expense of de novo responses; this ‘primary addiction’ can be overcome by boosting with variant antigens.

Deep learning algorithms perform as well as humans in identifying cells in tissue images.

A newly developed genetically engineered mouse model enables the analysis of specific antigen presentation in vivo, providing insights into the tumour immunopeptidome and cancer progression.

Influenza virus neuraminidase (NA) is a drug target and a potential vaccine antigen. Here, the authors provide a detailed analysis of the conformational stability of NA, and show how expression and stability of recombinant NA antigens can be strengthened through structure-based design.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

In a mouse tumour model, immunotherapy-induced rejection of tumour cells requires presentation of both MHC class I and MHC class II antigens, which activate CD4⁺ and CD8⁺ T cells, respectively.

The complex interplay between the multiple pathogenic factors that underlie uremic bleeding syndrome is yet to be fully elucidated. As such, guidelines on management of this complication of chronic renal failure are lacking. Here, data from clinical trials of dialysis, erythropoietin, cryoprecipitate, desmopressin and conjugated estrogens have been used to develop a treatment algorithm. This decision aid is accompanied by answers to questions that commonly arise during management of uremic bleeding.

Tarpey et al. carry out a large-scale systematic sequencing of the majority of X-chromosome coding exons from 208 families with multiple individuals with mental retardation and a pattern of transmission compatible with X linkage in order to identify XLMR-causative mutations. They find several mutations that appear to be causative in loci already known to be involved in XLMR, as well as new data about those loci, and make inferences about the role of the different classes of variants in these diseases.

Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.

PIWI-interacting RNAs (piRNAs) suppress transposon and gene expression during development. Here, the authors identify many piRNAs and piRNA-like small RNAs in 11 human cell lines, and show that one piRNA-like small RNA binds to phosphorylated ERM proteins to regulate cancer cell migration and invasion.

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’.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

Clonal dynamics are inferred from mitochondrial variants in primary human cells.

Immune checkpoint therapy is beneficial for patients with advanced bladder cancer; however, trials generally exclude patients with comorbidities or uncommon histologies. The SAUL trial demonstrates that atezolizumab is safe and efficacious in a patient population that more accurately reflects the real-world scenario, but its benefit might still be limited in historically poorly performing populations.