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COMET, an artificial intelligence method that improves the analysis of small medical studies using large clinical databases, has been created. COMET can help develop better artificial intelligence tools and identify key biomarkers across many diseases, potentially changing medical research.

Longitudinal shotgun metagenomics reveal changes in the gut microbial ecology upon carbapenemase-producing Enterobacteriaceae colonization and decolonization of adult subjects.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

Soybean is made resistant to Asian soybean rust using a gene cloned from pigeonpea, showing that legumes may contain a reservoir of disease-resistance genes.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

While greater yam provides food and income security for millions of people around the world, there are limited genomic resources available. Here, the authors report a chromosome-scale assembly of the greater yam genome as well as quantitative trait loci associated with anthracnose resistance and tuber traits.

Large sequences are integrated site specifically into the human genome without double-strand DNA cleavage.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

Is there an optimum difficulty level for training? In this paper, the authors show that for the widely-used class of stochastic gradient-descent based learning algorithms, learning is fastest when the accuracy during training is 85%.

Due to the polygenic nature of most diseases, simultaneous correction or introduction of single nucleotide variants is needed. Here, the authors demonstrated the feasibility of multiplex base editing for polygenes disease modeling in cynomolgus monkey embryos with high specificity.

Complement factor H (FH) binds complement 3b and promotes the stepwise degradation of C3b to C3d, protecting self cells from being mistakenly recognized as foreign. A previous structure showed how CCP modules 1–4 of FH bind C3b; this study now shows the interaction of CCP modules 19–20 with C3d and builds a model for the interaction of the complete FH molecule with C3b.

Vilazodone (VLZ) is a drug for the treatment of major depressive disorders that targets the serotonin transporter (SERT). Here, the authors combine pharmacology measurements and cryo-EM structural analysis to characterize VLZ binding to SERT and observe that VLZ exhibits non-competitive inhibition of serotonin transport and binds with nanomolar affinity to an allosteric site in SERT.

Analyses of tumor and bone marrow tissue from patients with glioblastoma demonstrate the presence of extracerebral niches that contained tumor-reactive and memory T cell subsets, including early stem-like phenotypes and stages, indicating antitumor CD8⁺ T cell differentiation in cranial bone marrow.

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.

Huang and colleagues used machine-learning estimators to analyse a broad range of parameters in a prospective cohort consisting ART and spontaneously conceived children. Small differences in stature and growth could not be explained by parental or perinatal environment factors, nor differences in fetal DNA methylation. No strong differences in metabolic parameters were seen.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with repetitive and restrictive behaviours. Here the authors integrate mRNA expression, miRNA expression, DNA methylation, and histone acetylation datasets from a collection of post mortem brain tissues and identify a convergent molecular subtype of ASD.

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.

C9orf72:SMCR8:WDR41 complex has been reported to have GAP activity for both ARF family proteins and the RAB proteins RAB8A and RAB11A. Here the authors provide structural and biochemical evidence for a specific function of the C9orf72 complex as an ARF GAP, and a structural framework for the GAP activity of the longin-containing GAP family.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Geospatial modelling shows an overall decline in morbidity and mortality due to lower respiratory infections in Africa from 2000 to 2017, but also identifies subnational areas with residual high risk.

Cavity polaritons whose matter component is composed of highly excited Rydberg atoms are shown to act as a zero-dimensional quantum dot. Trapping 150 polaritons led to the observation of blockaded photon transport.

Structural, functional and in silico analyses of the chloroquine-resistance transporter PfCRT of Plasmodium falciparum suggest that distinct mechanistic features mediate the resistance to chloroquine and piperaquine in drug-resistant parasites.

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.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Jonathan Carlson and colleagues report that pre-adaptation of HIV to a recipient's major histocompatibility complex class I alleles impairs immune control of the virus.

The molecular mechanisms underlying the Bezold–Jarisch reflex and syncope (fainting) involve vagal sensory neurons that express neuropeptide Y receptor Y2, the deletion of which in animal models abolishes the Bezold–Jarisch reflex.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Self-limited assembly of 'imperfect' chiral nanoparticles enables formation of bowtie-shaped microparticles with size monodispersity and continuously variable chirality to be used for printing photonically active metasurfaces.

A cryo-EM structure of SARS-CoV-2 ORF3a reveals a new fold conserved in coronaviruses, and functional experiments show ion channel activity that may be important for viral infectivity.

Whole-genome sequencing of more than 2,000 colorectal carcinoma samples provides a highly detailed view of the genomic landscape of this cancer and identifies new driver mutations.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Quek et al. survey endoscopists across ten Asian countries, exploring their perspectives on the use of artificial intelligence in gastrointestinal endoscopy. Perceived benefits, adoption barriers, research priorities, and the proposed role of an Asia AI Task Force are detailed.

Jones et al. examine the generalizability of the valence–dominance model of social judgements of faces in 41 countries across 11 world regions. They find evidence of both generalizability and variation, depending on the analytical method.

The black phase of formamidinium lead iodide perovskite is used to make highly efficient solar cells, and a technique to improve its purity and stability by controlling crystal nucleation could make them even better.

This analysis of single-cell RNA sequencing data from peripheral blood mononuclear cells for 474 individuals of diverse Asian ancestries in the Asian Immune Diversity Atlas links cell-type-specific splicing variation with autoimmune and inflammatory disease risk.

Transition metal complexes that display slow magnetic relaxation show promise for information storage, but our mechanistic understanding of the magnetic relaxation of such compounds remains limited. Here, the authors spectroscopically and computationally characterize the strength of spin–phonon couplings, which play an important role in the relaxation process.

Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.

An NMR fragment screen identified a small molecule that binds to an allosteric site on the proapoptotic protein BAX and synergizes with the BIM BH3 domain to conformationally activate BAX and enhance BAX-mediated membrane poration.

vTwINS enables high-speed volumetric calcium imaging via a V-shaped point spread function and a dedicated data-processing algorithm. Song et al. apply this strategy to image population activity in the mouse visual cortex and hippocampus.

Fault-tolerant quantum computing would require very high accuracy in quantum gate characterisation. Here, the authors introduce an optimal low-depth phase estimation method inspired by quantum signal processing, significantly improving gate calibration accuracy.

Interfacing living systems with electronics for biosensing and biocomputing applications is challenging. Here, Gao et al. present hybrid transistors with electroactive bacteria capable of extracellular electron transfer, enabling transduction of biological computations to electrical readouts.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Designing mechanical metamaterials is challenging because of the large number of non-periodic constituent elements. Here, the authors develop an approach to design arbitrarily shaped metamaterials that is more computationally efficient by six orders of magnitude compared to other approaches.