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Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

Candida albicans must adapt to hypoxia. Here, the authors discover the sterol C4-methyl oxidase (SMO) Erg251 is essential for extreme hypoxic growth, as well as virulence and colonization, and that SMO inhibitors have therapeutic potential.

The intestinal microbiome is shaped by genetics and environment. Here, the authors show in rats that host genetic effects, including indirect social effects, influence microbiome composition, identify replicated loci, and reveal mechanisms contributing to microbiome heritability.

Known to augment host innate immunity, Zhou and Ahearn et al. shows that a SARS-CoV2 NSP15 mutant also increases viral recombination and reduces sub-genomic message. Results articulate a novel role for NSP15 in viral transcription and recombination.

In colorectal cancer, therapeutic resistance is driven by MAPK-dependent epithelial cell plasticity.

McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

Here, using metagenomics, the authors comparatively characterize the development of the gastric residuals and stool microbial communities in premature infants, with the microbiota in gastric residuals exhibiting less stability over the hospitalization period.

Building an academic career increasingly calls for greater public engagement, particularly in subjects with more societal relevance such as climate change. Leah Stokes discusses some of the difficulties she has faced in striking a balance between her academic responsibilities and her public work.

In this work, authors utilise a prefractionation natural product extract screening platform, which uncovers coniotins, lipopeptaibiotics with broad antifungal activity and a mechanism of action that targets fungal cell wall β-glucan.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

In vivo gene editing hinges on identifying an ideal delivery vehicle from numerous candidates. Here, authors establish the GFP-on mouse model capable of translating successful adenine base editing to a fluorescent readout thus enabling the rapid evaluation of genome editing delivery vehicles.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Thousands of genetic variants have been associated with lupus, but causal variants and mechanisms are unknown. Here, the authors combine a massively parallel reporter assay with genome-wide ChIP experiments to identify risk variants with allelic enhancer activity mediated through transcription factor binding.

The enteric nervous system integrates microbial cues to regulate gut function. Using an optogenetic gut culture model, authors show lineage- and frequency-specific neuronal control of immune responses and barrier integrity, shaped by gut microbes.

DNA sequencing methods for characterizing microbial communities are well developed for bacteria, archaea and fungi, but less so for eukaryotic parasites and commensals. Here, the authors present an optimized and validated metabarcoding protocol for host-associated eukaryotic communities.

Single-cell sequencing approaches need to balance sensitivity, throughput and experimental complexity. Here the authors combine droplet-based microfluidics and combinatorial indexing to develop OAK, a versatile method for ultra-high throughput single-cell multiomic profiling.

In this genomic analysis of peripheral blood samples of the phase 3 CheckMate-067 trial of ipilimumab (IPI) versus nivolumab (NIVO) versus ipilimumab and nivolumab (IPI-NIVO) in melanoma, the status of certain mitochondrial haplogroups in patients was associated therapeutic resistance to NIVO or IPI-NIVO, a finding validated in an independent cohort.

A growth-coupled biosynthetic pathway enables xathommatin synthesis in the soil bacterium Pseudomonas putida.

The antibacterial agent colistin displays synergistic activity with azoles and echinocandins against various pathogenic fungi. Here, the authors show that the mechanisms involve disruption of cell membrane permeability and calcium homeostasis.

Cellular lysine residues can be both methylated and acetylated on the same sidechain to form N^ε-acetyl-N^ε-methyllysine (Kacme), which is found on histone H4 across a range of species and across mammalian tissues and is associated with active chromatin.

Single cell RNA-sequencing can be a powerful approach to characterizing cell composition in a population of cells but is thought to be too expensive for population-scale analyses. Here, the authors show how lower coverage of more samples can increase the power to detect cell-type-specific eQTL.

A massively parallel assay developed to map the essential photosynthetic enzyme rubisco showed that non-trivial biochemical changes and improvements in CO₂ affinity are possible, signposting further enzyme engineering efforts to increase crop yields.

Time-resolved RNA–protein cross-linking with a pulsed femtosecond ultraviolet laser, followed by immunoprecipitation and high-throughput sequencing, enables the determination of binding and dissociation kinetics of the RNA-binding protein DAZL within cells.

The transcription factor double homeobox protein (DUX) induces a totipotency-specific regulatory program, including the upregulation of DUXBL. DUXBL subsequently accesses DUX-bound regions and interacts with TRIM24 and TRIM33, thus contributing to totipotency exit.

An optically addressable fluorescent-protein spin qubit is realized using enhanced yellow fluorescent protein; the qubit can be coherently controlled at liquid-nitrogen temperatures and the spin detected at room temperature in cells.

Antibiotic-resistant bacteria are an urgent threat to human health. Here, Roberts et al. characterise and monitor an ongoing hospital outbreak of carbapenemase-producing Enterobacter hormaechei by integrating several technologies for whole-genome sequencing and shotgun metagenomics.

Recurrent urinary tract infections occur in ~ 25% of women. Here, Beatson and colleagues use whole genome sequencing to track the dynamics of an E. coli ST131 clone in a single patient over a 5-year period. This study provides unique insights into pathogen evolution during recurrent urinary infection.

In the phase 2 study LCCC1520 (NCT02690558), clinical activity of pembrolizumab in combination with gemcitabine and cisplatin as neoadjuvant therapy in patients with muscle-invasive bladder cancer has been reported. Here the authors present molecular and immune cellular features associated with response to neoadjuvant chemo-immunotherapy.

During spermatogenic meiosis, chromatin changes due to transcription, homologous recombination, and chromosome synapsis must be coordinated. Here they show that A-MYC and BRDT regulate release of paused RNA PolII to induce a transcriptional burst during pachytene of prophase I.

Chan et al. report that 3′ UTR splicing is widespread and enhanced across different cancer types and is associated with more advanced tumour progression.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Using long reads to probe RNA structure reveals differences between transcript isoforms.

Using 1,854 routinely collected clinical samples from early in pregnancy, with validation in an external cohort, low-coverage cfDNA sequence data identified distinctive features among those who developed preeclampsia.

Previously, authors have identified GW461484A (GW) as an inhibitor of the kinase Yck2 in the fungal pathogen Candida albicans. Here, they report the synthesis of GW analogs with improved pharmacological properties and activity in mouse models of systemic candidiasis.

There is an urgent need for novel strategies to combat life-threatening fungal infections. Here, Revie et al. identify a compound that induces alterations in fungal membranes, synergizes with azole antifungals against the pathogen Candida albicans, and inhibits virulence traits and biofilm formation in animal models of infection.

Several pathogenic fungi such as Candida albicans undergo transitions between single-celled forms and multicellular filaments. Here the authors perform a genome-scale analysis of C. albicansand show that, contrary to common belief, filamentation is not required for escape from host immune cells.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Jonathan Pritchard, Christopher Garcia and colleagues examine associations between different T cell receptor V genes and MHC alleles by eQTL mapping. They find that there are strong associations between MHC variation and T cell receptor gene usage and map these signals to specific MHC amino acids, many of which physically interact with germline-encoded amino acids on the T cell receptor.

In this Viewpoint article, we asked five Black cancer researchers and clinicians to present their ideas on how we can attract and retain more diverse researchers to the cancer community and how we begin to close the gap in cancer disparities.