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Third-generation sequencing can reveal information beyond the simple sequence of bases, but fulfilling this potential requires complex reference sets for training. Here, the authors present an approach to generate these reference sets and present various use cases for such multidimensional sequencing.

In this work, authors show that randomized water, sanitation, hygiene and nutrition interventions reduced child antibiotic use in Bangladesh (in parallel with high intervention uptake and reduced infections) but not Kenya (in parallel with lower uptake and no effect on infections).

Magnetoencephalography in human participants paired with Rapid Invisible Frequency Tagging reveals that excitability in early visual cortex is modulated to boost targets and suppress distractors in guided visual search.

Interactions between electroactive bacteria and metal oxides are used for bioremediation. Here, the authors report on the application of Fe(III)-containing metal organic frameworks as substrates for bacterial growth which allow for remediation of lethal levels of chromium with high efficacy over several cycles.

PRC2 preferentially binds G tracts within nascent pre-mRNAs, causing transfer of PRC2 from chromatin to RNA upon gene activation, thus providing a mechanism to selectively remove PRC2 from specific genes.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

Single-molecule studies allow biological processes to be examined one molecule at a time, as they occur. Here, zero-mode waveguides have been used to concentrate reactions in zeptolitre-sized volumes, making it possible to study real-time translocation by the ribosome. The binding of transfer RNAs (tRNAs) to the ribosome could be followed; the results show that tRNA release from the exit site is uncoupled from tRNA binding to the aminoacyl-tRNA site.

Petsch et al. apply mRNA vaccination for the first time to infectious disease, demonstrating immunogenicity and/or protective effects against influenza virus in mice, ferrets and pigs.

Analysis of bronchoalveolar lavage fluid samples from patients with SARS-CoV-2-induced respiratory failure suggests that SARS-CoV-2 infects alveolar macrophages to cause release of T cell chemoattractants, thereby inducing local inflammatory cytokine release and further T cell activation, ultimately resulting in a positive feedback loop that drives alveolar inflammation.

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.

While the analysis of SARS-CoV-2 RNA in stool samples has led to important insights regarding the disease, quantification is currently challenging. Here the authors use patient samples to benchmark preservation, extraction and quantification methods to optimise detection of viral RNA.

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations.

Interactions with other microbes may inhibit or facilitate the dispersal of bacteria. Here, Zhang et al. use cheese rind microbiomes as a model to show that physical networks created by filamentous fungi can affect the dispersal of motile bacteria and thus shape the diversity of microbial communities.

Quantum-dot spin qubits in Si/SiGe quantum wells require a large and uniform valley splitting for robust operation and scalability. Here the authors introduce and characterize a new heterostructure with periodic oscillations of Ge atoms in the quantum well, which could enhance the valley splitting.

This Review discusses quantum optimization, focusing on the potential of exact, approximate and heuristic methods, core algorithmic building blocks, problem classes and benchmarking metrics. The challenges for quantum optimization are considered, and next steps are suggested for progress towards achieving quantum advantage.

This Perspective discusses how the Somatic Cell Genome Editing Consortium aims to accelerate the implementation of safe and effective genome-editing therapies in the clinic.

Bacterial–fungal interactions are studied using a combination of random barcode transposon-site sequencing, RNA sequencing, bacterial cytological profiling and metabolomics. Fungi cause widespread changes in the fitness of bacterial mutants and have both conserved and species-specific impacts on bacteria.

PoxA is a lysyl-tRNA synthetase paralog that post-translationally modifies elongation factor P (EF-P) with a lysine moiety. Further biochemical analysis reveals that (R)-β-lysine, rather than the more abundant α-amino acid, is the preferred substrate for PoxA.

Over the past decade, Kīlauea and Mauna Loa—adjacent volcanoes in Hawai‘i—have inflated and deflated in tandem, yet their shallow volcanic plumbing systems are separate. Numerical modelling of the volcanoes shows that dynamic stress transfer by asthenospheric pore pressure is a viable mechanism for volcano coupling in Hawai‘i.

Genome-wide analyses identify multiple loci associated with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and left ventricular (LV) traits. Cardiomyopathies exhibit strong genetic correlations with LV traits, with opposing effects in HCM and DCM.

Meningiomas are heterogeneous tumours. Here, the authors analysed genetic, epigenetic, and transcriptomic features across spatially-distinct meningioma samples to identify molecular programs underlying tumorigenesis that can be detected preoperatively using magnetic resonance imaging.

Spirulina is used to manufacture a therapeutic antibody against campylobacter.

High-grade gliomas functionally remodel neural circuits in the human brain, promoting tumour progression and impairing cognition.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

Disease-causing microduplications can be corrected by harnessing an endogenous double-stranded break DNA repair pathway.

Robert Hegele and colleagues report a genome-wide association study for hypertriglyceridemia, followed by resequencing of the coding regions of candidate genes. They identify an excess of rare variants in affected individuals at four genes within the associated loci.

The analysis of T-cell antigens in long-term survivors of pancreatic ductal adenocarcinoma suggests that neoantigen immunogenicity and quality, not purely quantity, correlate with survival.

Optimized conditions for ribonucleoprotein delivery of Cas9–sgRNA complexes enables precise and efficient gene editing to restore fetal hemoglobin expression in sickle cell disease patient-derived HSCs

A manipulative experiment in which a reef is alkalinized in situ shows that calcification rates are likely to be lower already than they were in pre-industrial times because of acidification.

Consuming diets rich in plant versus animal products changes the microbes found in the human gut within days, with important implications for our health and evolution.

A diagnostic tool based on blood RNA-seq is shown to identify causal genes and variants linked to clinical phenotypes in individuals with rare diseases for which whole-exome genetic sequencing was uninformative.