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AlphaStar uses a multi-agent reinforcement learning algorithm and has reached Grandmaster level, ranking among the top 0.2% of human players for the real-time strategy game StarCraft II.

Influenza A virus infection causes a dramatic upregulation of ADP-ribosylation that as part of the cellular antiviral response, a process that is counteracted by the viral NS1 protein.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Genomic analyses of heartworms from multiple continents suggest a deeper evolutionary origin in canids than previously recognised, with evidence of both ancient dispersal events and more recent introductions linked to human movement.

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.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Andrew Robinson reviews five of the week’s best science picks.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

SMARCA4 loss in non-small-cell lung cancer creates a metabolic dependency on oxidative phosphorylation that can be targeted using a new small-molecule inhibitor.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Integrated data, including 100 human genomes from the Mesolithic, Neolithic and Early Bronze Age periods show that two major population turnovers occurred over just 1,000 years in Neolithic Denmark, resulting in dramatic changes in the genes, diet and physical appearance of the local people, as well as the landscape in which they lived.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Individual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration challenging. Here, the authors propose a Bayesian optimization framework to calibrate a complex malaria transmission simulator.

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.

Healthcare emissions negatively affect the environment and health, posing ethical questions between health and environmental impacts. A focus group study in US health systems revealed a willingness to make environmentally informed health decisions and identified barriers to making such decisions.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

Although pathogen whole genome sequencing is becoming more common, for many pathogens far more partial sequences are available. In this study, the authors develop a phylogenetic pipeline to efficiently combine whole and partial viral genome sequences and demonstrate its application using rabies virus sequences.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Researchers trying to work out whether global warming will cause more wars need to stop fighting and work together, urges Andrew R. Solow.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Natsuhiko Kumasaka, Andrew Knights and Daniel Gaffney develop a new statistical approach for association mapping that models genetic effects and accounts for biases in sequencing data in a single probabilistic framework. They apply this method to generate a map of chromatin accessibility QTLs and show how it can be used to fine-map regulatory variants and link distal regulatory elements with genes.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Microtubule-destabilizing drugs and oncolytic viruses are two unrelated approaches to battle cancer. Here the authors show that microtubule-destabilizing drugs potentiate the efficiency of oncolytic rhabdoviruses by altering the cytokine production and response of the tumour cells.

The influence of climate on premodern civil conflict and societal instability is debated. Here, the authors combine archeological, historical, and paleoclimatic datasets to show that drought between 1400-1450 cal. CE escalated civil conflict at Mayapan, the largest Postclassic Maya capital of the Yucatán Peninsula.

Andrew Robinson enjoys a history of a controversial probability tool — Bayes' theorem.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

The authors of some of our most popular Reviews look back on a decade of immunology.

World wars, cold wars, cyberwars — marking a century of state surveillance at GCHQ.

Topoisomerases facilitate the progress of elongating polymerases during transcription. Zomerdijk and colleagues now demonstrate an additional role for this enzyme; their data suggest that Top2 can cleave DNA inducing topological changes at the ribosomal DNA promoter, which assists de novoassembly of the RNA polymerase I pre-initiation complex.

A newly designed thiol catalyst for radical cyclization reactions is the result of a long and storied battle to control the reactivity of carbon-centred radicals.

AMPA receptors are a class of protein complexes crucial for neuronal communication. Two complementary studies converge on structures of AMPA receptors found in a brain region called the hippocampus.

The growth of single-crystal Prussian blue analogues and their analysis using X-ray diffuse scattering reveals diverse, non-random vacancy arrangements and information about the micropore-network characteristics of these materials.

The Red Queen metaphor has species accumulating small changes to keep up with a continually changing environment, with speciation occurring at a constant rate. This constant-rate claim is now tested against four competing models, using 101 phylogenies of animal, plant and fungal taxa. The results provide a new interpretation of the Red Queen; a view linking speciation to rare stochastic events that cause reproductive isolation.

Mary Relling and colleagues explore the effects of ancestry on the pharmacogenomics of relapse in acute lymphoblastic leukemia. They found that Native American ancestry was associated with risk of relapse but that differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy.

Using machine learning techniques applied to multimodal UK Biobank data, Wen et al. characterize the genetic basis of the biological age gaps of individual organs, uncovering interorgan cross-talk and links between chronic diseases, lifestyle factors and biological age gaps.

Following the success of the inaugural games, the Microbial Olympics return with a new series of events and microbial competitors. The games may have moved to a new hosting venue, but the dedication to training, fitness, competition (and yes, education and humour) lives on.

Polly Matzinger and her colleagues have shown that in the absence of B cells, and in the presence of the microbiota, the intestinal epithelium launches its own immune defense mechanisms. However, this comes at the expense of metabolic programs involved in fat absorption by the gut. These results could explain the lipid malabsorption often seen in humans with common variable immunodeficiency or with HIV infection.

Plasmodium vivax generally accounts for a low proportion of malaria cases in Africa, but population-level data on the distribution of infections is limited. Here, the authors use data from the Democratic Republic of the Congo and show that the prevalence is low (~3%) and diffusely spread.