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Using unique barcodes for tumour cells, the authors explore the dynamics of human glioblastoma subpopulations, and suggest that clonal heterogeneity emerges through stochastic fate decisions of a neutral proliferative hierarchy.

Sampling the viromes of vertebrates, arthropods and plants on an island ecosystem shows that viral transmission between species is strongly affected by phylogeny but less affected by predator–prey relationships and that generalist viruses pose the greatest zoonotic risk.

We gathered genetic data for 1,763 individuals from 147 populations across 14 African countries, and 12 Late Iron Age individuals, to trace the expansion of Bantu-speaking peoples over the past 6,000 years.

A field investigation at a former nuclear waste disposal site shows how environmental stress modulates subsurface microbial community assembly.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

Using pancreatic organoids and genetic mouse models, Antonucci et al. show that cellular stress activates an NRF2–EZH2 epigenetic axis leading to metabolic reprogramming and subsequent malignant transformation of KRAS-mutant benign lesions.

Connecting genomics and proteomics allows the development of more efficient and specific treatments for cancer. Here, the authors develop proteogenomic methods to defining cancer signaling in-vivo starting from core needle biopsies and with application to a HER2 breast cancer focused clinical trial.

Seeber et al. studied brain recordings from implanted electrodes in freely moving humans. Neural dynamics encoded actual and imagined routes similarly, demonstrating parallels between navigational, imaginative and mnemonic abilities in the human brain.

Analyses of 475 ancient horse genomes show modern horses emerged around 2200 bce, coinciding with sudden expansion across Eurasia, refuting the narrative of large horse herds accompanying earlier migrations of steppe peoples across Europe.

Single-molecule FRET imaging provides insights into the allosteric link between the ligand-binding and G-protein nucleotide-binding pockets of the β₂ adrenergic receptor (β₂AR) and improved understanding of the G-protein activation mechanism.

Reducing topoisomerase activity in mouse and human neurons is found to reduce the expression of long genes by impairing transcription elongation: among genes affected are numerous high-confidence candidates for autism spectrum disorder.

A 16-year dataset of abundance patterns of a diverse assemblage of bees in New Mexico, USA predicts declines for many bee species and indicates that drought-tolerant taxa will prevail in a warming and drying climate.

Here the authors uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in leukemia. The work pointed to the potential of targeting the posttranscriptional circuitry via CNOT3 as a therapeutic vulnerability in acute myeloid leukemia.

Bispecific CAR T cells targeting CD19 and CD22 exhibit clinical activity and low toxicity in patients with large B cell lymphoma and B cell acute lymphoblastic leukemia, with relapses associated with loss of CD19 but not CD22.

Neurotransmitter:Na⁺ symporters (NSS) remove neurotransmitters from the synapse in a reuptake process that is driven by the Na⁺ gradient. Here, single-molecule fluorescence imaging assays have been combined with molecular dynamics simulations to probe the conformational changes that are associated with substrate binding and transport by a prokaryotic NSS homologue, LeuT. The findings are interpreted in the context of an allosteric mechanism that couples ion and substrate binding to transport.

A large-scale meta-analysis across eight biobank datasets identifies common genetic variants associated with mosaic loss of the X chromosome in female participants.

Genome-wide association meta-analysis across individuals of diverse ancestries identifies risk loci for nonalcoholic fatty liver disease. The associated variants implicate plausible biological pathways and improve estimates of disease risk.

Sociality explains substantial variation in ageing across species, but less is known about this relationship within species. Here, the authors show that female dominant Seychelles warblers with helpers at the nest have higher late-life survival and lower telomere attrition and the probability of having helpers increases with age.

Navigating through everyday environments requires the ability to keep track of others. Here, the authors show this ability is linked to grid-like codes in the human entorhinal cortex that signal the spatial paths other individuals take.

Cancer RNA-seq data are normalized with respect to library size, tumor purity and batch effects.

The Finnish population is enriched for genetic variants which are rare in other populations. Here, the authors find new genetic loci associated with 1391 circulating metabolites in 6136 Finnish men, demonstrating that metabolite genetic associations can help elucidate disease mechanisms.

Camelina sativa is an oilseed crop with important industrial applications. Here, the authors sequence the C. sativagenome to investigate the genome organization and evolution of this species, and to provide a valuable tool for genetic engineering and potential crop improvement.

Zihni et al. discover a role for Cdc42–MRCK signalling in establishing contractility at the apical pole, which in turn controls epithelial polarity in mammalian cells and Drosophila photoreceptors.

Genetically engineered mouse models representing the spectrum of human cutaneous melanoma provide a platform for studying clinical responses to immunotherapy.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

Single-cell CRISPR screens are readily multiplexed and scaled with an improved version of Perturb-seq.

Although Huntington’s disease (HD) is a well-studied genetic disorder, less is known about the epigenetic changes underlying it. Here, the authors characterize DNA methylation levels in tissues from patients, a mouse huntingtin (Htt) gene knock-in model, and a transgenic HTT sheep model, and provide evidence that HD is accompanied by DNA methylation changes in these three species.

The developing mouse gut endoderm, mapped at single-cell resolution, reveals trajectories of cell differentiation before and during gastrulation and the emergence of regionalized cell identities along the anterior–posterior axis of the gut tube.

Herold et al. present an integrated meta-omics framework to investigate how mixed microbial communities, such as oleaginous bacterial populations in biological wastewater treatment plants, respond with distinct adaptation strategies to disturbances. They show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity.

Symbiotic fungi control network-level structure and flows to meet trade demands.

Christian Gilissen, John Niederhuber and colleagues examine de novo mutations with parent-of-origin information from whole-genome sequencing datasets from 816 parent–offspring trios. They find maternal and paternal specific mutation signatures that are more prominent with increased age of the parent as well as clustered mutation signatures with no parental bias.

APC is a well-known tumour suppressor that is frequently inactivated in colorectal cancer. Here, the authors sequence more than 1000 cancer genes in 468 colorectal cancers and show that mutation signatures can be used to classify the tumours and that multiple mutations in APCare associated with a poor prognosis.

The molecular mechanisms that regulate intestinal Clu+ revival stem cells (revSCs) and their niche to enable regeneration in response to injury are unclear. Here, the authors show that mice without the phospholipid transport protein, TNFAIP8, causes less revSCs to be induced following injury.

In individuals diagnosed with age-related macular degeneration in one eye, a deep learning model can predict progression to the ‘wet’, sight-threatening form of the disease in the second eye within a 6-month time frame.

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.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

The combination of in situ hybridization of fluorescent probes onto chromosomes in solution and flow cytometry allows the quantitative identification of repeat sequences in individual chromosomes.

Selected reaction monitoring (SRM) is a powerful mass spectrometry technology to reliably detect selected protein targets, even those at very low abundance, but requires tedious assay development for each protein of interest. High-throughput SRM assay development is now possible by using crude synthetic peptide libraries without purification to represent each protein target.

Mutations in the transcription factor MEF2B are found in diffuse large B-cell lymphoma. In this study, the authors map the DNA-binding sites of the transcription factor in cells in vitroand find that the mutations decrease the ability of MEF2B to activate transcription.

Microglia mediate the early and selective degeneration of corticostriatal synapses and the development of cognitive deficits in presymptomatic Huntington’s disease via the complement cascade.

The identification of mRNA targets for RNA binding proteins (RBP) in stem cells is difficult due to the limited number of available cells. Here, as a proof-of-principle, the authors adapt the HyperTRIBE method to find that an RBP, MSI2, has increased RNA binding in leukemic compared with normal stem cells for selective regulation of oncogenic genes.

Melanocortin receptor accessory protein 2 (MRAP2) is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling. Here the authors show that MRAP2 also regulates ghrelin receptor signalling in the hypothalamus and starvation sensing in mice.