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Analysis of colorectal cancer bulk gene expression data at the pathway level identifies a poor-prognosis subtype associated with cell differentiation. The subtypes are reproducible in single-cell data and offer biological insights beyond existing stratification strategies.

In a phase 2 trial of patients with untreated, recurrent and progressive brain metastases treated with an anti-programmed cell death protein 1 inhibitor, the overall intracranial benefit rate was 42.1%, which met the prespecified primary endpoint.

Of 12 serology assays tested, four detect antibodies in more than 80% of patients with COVID-19.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The mechanisms underlying drought-induced tree mortality are not fully resolved. Here, the authors show that, across multiple tree species, loss of xylem conductivity above 60% is associated with mortality, while carbon starvation is not universal.

A conjugative plasmid isolated from Thermococcus enables interspecies transfer across Archaea, whether naturally competent or not, and at temperatures up to 100 °C.

Sakata et al. performed a prospective personalized mechanistic computational (digital twin) study focused on characterizing the arrhythmogenic properties of the atrial fibrotic substrate in patients with persistent atrial fibrillation, and they introduce here a novel mechanism-oriented strategy for optimal ablation.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Computational search identifies dynobactin A which is a systemically active, natural-product peptide antibiotic that kills Gram-negative bacteria.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Due to the complex, nonlinear and correlated nature of accelerator systems, electron beam property optimisation is a time-consuming process. Here, the authors utilise multi-objective Bayesian active learning for speeding up online beam tuning at MeV ultrafast electron diffraction facility.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

The development of IDH variant inhibitors is a breakthrough as it is the first time metabolism has been successfully targeted by small molecule drugs in cancer. Here the authors report studies on resistance to the pioneer drug ivosidenib leading to identification of inhibitors retaining activity.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Transcriptional activity in plants is controlled with a programmable gene circuit.

It is not clear how agricultural intensification affects spatially coupled ecosystems. Here, the authors use long-term datasets on managed grasslands coupled with unmanaged wetlands showing that grassland intensification affects ecosystem service multifunctionality of spatially coupled wetlands

Radio pulses from a rare, radio-loud magnetar, XTE J1810−197, are seen to have undergone a conversion in their polarization state. This change can be linked to the magnetar’s magnetic field geometry, and has commonalities with an effect also seen in fast radio bursts.

Provora is an ancient supergroup of microbial predators that are genetically, morphologically and behaviourally distinct from other eukaryotes, and comprise two divergent clades of predators—Nebulidia and Nibbleridia—that differ fundamentally in ultrastructure, behaviour and gene content.

An analysis of the Drosophila connectome yields all cell types intrinsic to the optic lobe, and their rules of connectivity.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Plasma from voluntarily running mice reduces baseline expression of neuroinflammatory genes and experimentally induced brain inflammation when infused into sedentary mice.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Optical observations of Dimorphos, a satellite of the asteroid 65803 Didymos, before, during and after the impact of the DART spacecraft, from a network of citizen science telescopes across the world are reported.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Male patients with COVID-19 have higher plasma levels of innate immune cytokines and chemokines such as IL-8, IL-18 and CCL5 and more non-classical monocytes than female patients, whereas female patients mount robust T cell activation maintained even in older age.

Using data from the Tara Pacific expedition, this study shows that a key driver of variation in coral telomere DNA length across the Pacific Ocean is the history of water temperature. The telomere lengths of short-lived, stress-sensitive Pocillopora colonies are more sensitive to seasonal temperature variations than those of long-lived and stress-resistant Porites colonies.

The Movember global Landscape Analysis Committee (LAC) was established to act as an independent group of experts across urology, medical oncology, radiation oncology, radiology, pathology, translational research, health economics and patient advocacy to identify the highest priority research needs across the prostate cancer biomedical research domain. Findings from the landscape analysis illustrate the research priorities in prostate cancer and will enable Movember to focus on specific needs, with particular investment in research to reduce disease progression and improve therapies for advanced prostate cancer.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

Explosive volcanic eruptions of Kīlauea in Hawaii can be explained by sudden subsidence of reservoir roof rock causing gas and lithic debris venting by a mechanism similar to that of a stomp rocket, according to seismic inversions for reservoir pressure changes.

A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.

Forecasts of COVID-19 mortality have been critical inputs into a range of policies, and decision-makers need information about their predictive performance. Here, the authors gather a panel of global epidemiological models and assess their predictive performance across time and space.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.

Studying microorganisms at high temperatures is challenging on conventional optical microscopes. Here, the authors introduce the concept of microscale laser heating over the full field of view by using gold nanoparticles as light absorbers, and study thermophile species up to 80 °C.

Guide RNA folding affects functionality of CRISPR-Cas transcriptional control systems. Here, the authors report computational gRNA design together with creation of synthetic CRISPRa promoters for orthogonal expression control and demonstrate the application in pteridine and human milk oligosaccharide production in E. coli.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

JWST observations reveal more than 17 nested dust shells that formed in the colliding winds of the massive binary WR 140 that enrich the surrounding interstellar medium with organic compounds and carbon-rich dust.

Metabolic dynamics within the small intestine are difficult to study due to the lack of in situ access. Here, the authors report an ingestible, self-powered, and wireless biosensing system, demonstrating proof-of-principle real-time glucose monitoring in the small intestines of pigs.

Single cell genome sequencing approaches have identified somatic copy number variants (CNVs) in human neurons, but small sample sizes (<100 neurons) have limited the power to find recurrent patterns such as CNV hotspots in a single individual. Here, the authors develop an approach to map CNVs in 2097 neurons from a neurotypical individual, finding that >10% neurons contain at least one somatic CNV, and enabling deeper investigation of these events.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

Cancer vaccines have had limited success in eliminating tumors in patients. Here Willem Overwijk and colleagues report that one reason for the failure of peptide-based vaccines may be their formulation. Their research shows that peptides formulated in incomplete Freund's adjuvant sequester CD8+ T cells at the site of injection, leading to T cell dysfunction and eventual apoptosis. A peptide and adjuvant formulation that did not persist long term at the injection site showed superior ability to induce a functional antitumor T cell response.

Erythropoiesis can be regulated by transcriptional, epigenetic, and post-transcriptional mechanisms. Here the authors report that N⁶-methyladenosine mRNA methyltransferase complex stimulates erythropoiesis by promoting translation of specific mRNAs.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

The catalytic subunit of DNA-PK autophosphorylates and contributes to ribosome biogenesis and haematopoiesis by binding to the U3 small nucleolar RNA.