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Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

By comparing data from real-world grassland communities with data from two of the longest-running grassland biodiversity–ecosystem functioning experiments, the authors show that conclusions derived from experimental systems are robust to the removal of unrealistic experimental communities.

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.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

Levantine Phoenicians made little genetic contribution to Punic settlements in the central and western Mediterranean between the sixth and second centuries bce; instead, the Punic people derived most of their ancestry from a genetic profile similar to that of Sicily and the Aegean, with notable contributions from North Africa as well.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Virus-specific CD8⁺ T cells are crucial during H7N9 influenza infection, but CD8⁺ T cell dysfunction is associated with poor prognosis. Here, the authors use molecular and phenotypic analysis to establish persistence of clonally diverse CD8⁺ T cell populations during fatal infection.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

The barrier function of skin epidermis requires polarized secretion of lamellar bodies towards the body surface. Here, Rudd et al. identify Flower (FWE) as a novel regulator of lamellar body trafficking and a determinant of epidermal barrier function.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

Clonally diverse and activated memory CD4⁺ T cells at baseline are associated with the development of severe immune-related adverse events, irrespective of the affected organ system, in patients with melanoma treated with immune checkpoint inhibitors.

By leveraging paired microbiome and human gene expression data from pediatric patients who underwent hematopoietic cell transplantation, distinct lung–immune system–microorganism interactions were identified as important drivers of fatal lung injury.

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.

A disturbed microbial network characterizes relapsing refractory Crohn’s disease and antedates disease recurrence after surgical removal of the active disease segment.

For T cells, functional antigen receptors are selected in the thymus from a pre-selection repertoire by interaction with self MHCs. Here the authors show that specific, non-germline coded features located in the complementarity determining region 3 of the pre-selection antigen receptors are essential for the selection of MHC-restricted repertoire.

The authors used mathematical modeling of human data to study how HIV persists despite suppressive antiretroviral therapy. They found that when latently infected CD4+ T cells proliferate or differentiate, they can create HIV DNA and passage it into other subsets. More mature CD4 cell subsets then clear HIV DNA faster.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Recovery of damaged ecosystems can vary in time and extent. Here, Moreno-Mateos and colleagues perform a meta-analysis to describe and quantify what they call recovery debt, an interim reduction in biodiversity, populations, and biogeochemical function of ecosystems during the recovery process.

Analysing changes in grasslands and savannahs following agricultural abandonment, the authors show that even after more than 90 years, plant diversity and productivity recovered by only 73% and 53%, respectively.

Mouse models of lung and colorectal cancer with sporadic DNA mismatch repair deficiency clarify that the intratumor heterogeneity and clonal architecture rather than tumor mutational burden are powerful determinants of immunotherapy response.

Kedzierska et al. report an association between low production of receptor-binding domain antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities, and show that this condition disproportionately affects Australia’s First Nations peoples because of the high burden of comorbidities in this population.

Only a subset of triple negative breast cancer patients respond to immunotherapy. Here, the authors analysed spatial immune contextures, which can be captured by a gene classifier, in relation to genomic alterations, mechanisms of T cell evasion and response to anti-PD1 treatment.

Survival during fasting requires release of adipose tissue lipid stores and is thought to be dependent on canonical lipases, including the rate limiting action of adipose triglyceride lipase. Here the authors show that lysosomes and lysosomal acid lipase play a critical role in adipocyte lipolysis with fasting in mice.

Triple negative breast cancers (TNBC) disseminate and metastasise, but the clonal relationship of metastases to primary tumours is poorly understood. Here, the authors use cellular barcoding of TNBC patient-derived xenografts and track the fate of barcoded clones in primary tumours and their metastases, including after resection or chemotherapy.

Isolating the relationships between biodiversity and ecosystem functioning in natural ecosystems is challenging. Here, the authors apply a causal inference approach to observational data from grasslands and find a negative effect of biodiversity on productivity driven by non-native and rare species.

Necrotizing soft tissue infections (NSTIs) are caused by a single pathogen such as Streptococcus pyogenes or by multiple bacterial species. Here, the authors integrate microbial community profiling with host and pathogen transcriptional analysis in patient biopsies, and identify an interferon-related signature specific to S. pyogenes NSTIs.

Improvements in European freshwater biodiversity occurred mainly before 2010 but have since plateaued, and communities downstream of dams, urban areas and cropland were less likely to experience recovery.

A single dose of a broadly neutralizing, HIV-specific antibody transiently reduces viral load in plasma, and in some individuals is associated with durable virus suppression in the absence of antiretroviral therapy.