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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.

The accuracy of melanoma diagnosis can vary considerably among clinicians, impacting both patient outcomes and the performance of related AI tools. Here, the authors systematically assess interrater variability among expert pathologists reviewing histopathological images and clinical metadata of melanoma-suspicious lesions collected at eight German hospitals.

Schneeberger, Kim, Geesdorf, Rajewsky, Heppner et al. tease IL-12 and IL-23 signaling apart in mouse models and human brain tissue to define a role for oligodendroglial and neuronal IL-12 signaling in neuroimmune crosstalk in Alzheimer’s disease.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Efficiency roll-off in organic light-emitting diodes under elevated current densities not only results in high power consumption but also device degradation. Here, the impact of polaroninduced quenching in efficiency roll-off was investigated and strategies to reduce efficiency roll-off were proposed.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Warming temperatures and interactions between plants are the main drivers of changes in Arctic plant communities in response to climate change, and there is no evidence of overall biotic homogenization.

Data on the effectiveness of a third dose of COVID-19 vaccine in pregnant women are limited. In this observational study, the authors report that a third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy enhances protection against maternal adverse COVID-19-related outcomes.

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.

Cleavage Under Targets & Tagmentation is a rapidly expanding technique, but thorough evaluation and benchmarking against established ChIP-seq datasets are required. This study shows that CUT&Tag recovers ~54% of ENCODE peaks for H3K27ac/H3K27me3 in K562 cells, with CUT&Tag peaks mapping to key cell type-specific regulatory regions.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

JMML is an aggressive hematologic malignancy with myeloproliferative characteristics affecting young children. Here the authors report that C-type lectin-like molecule-1 (CLL-1) is upregulated in JMML and they develop CLL-1 CAR T cells showing in vitro and in vivo anti-JMML activity.

PHDGH heterogeneity in primary tumours could be a sign of tumour aggressiveness.

Artificial intelligence has become popular as a cancer classification tool, but there is distrust of such systems due to their lack of transparency. Here, the authors develop an explainable AI system which produces text- and region-based explanations alongside its classifications which was assessed using clinicians’ diagnostic accuracy, diagnostic confidence, and their trust in the system.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Zhang, Dorn, Gnutti et al. identify pathogenic PPCS variants in people with PPCS deficiency disorder. Cardiac cells exhibit impaired contractility and arrhythmias, which is partially rescued by pantethine treatment.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

HGF/c-MET upregulation is frequent in bladder cancer. Here, the authors show that HGF induces EMT and invasion by stabilising TGFβ receptor through inhibition of the SMURF2 ligase, and the combined blockade of MAPK and TGFβ pathways suppresses HGF-mediated bladder cancer progression.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

Mutations in cancers can generate neoepitopes which can be recognized by different specific T cell receptors (TCR) with varying functional avidity. Here the authors show using xenogenic mouse models that antigen reactive TCR-engineered T cells expressing TCRs from a cancer patient with differing functional avidity have differential persistence and function in vivo.

Reengineering polyketide synthase encoding genes to produce analogues of natural products can be slow and low-yielding. Here the authors use accelerated evolution to recombine the gene cluster for rapid production of rapamycin-related products.

Analysis of changes in plant species richness on mountain summits over the past 145 years suggests that increased climatic warming has led to an acceleration in species richness increase.

Myasthenia gravis (MG) is a rare autoantibody-mediated disease affecting the neuromuscular junction. Here, the authors discover common genetic variation associated with the disease, increasing understanding of the genetic basis.

Maternal anti-SARS-CoV-2 antibodies can provide protection against severe COVID-19 in infants, but the relative protection conferred by maternal infection, vaccination, and hybrid immunity is unknown. Here, the authors use data from Israel and show that infants born to mothers with hybrid immunity had lowest rates of COVID-19 hospitalisation.

Here, the authors use genome-scale in vivo CRISPR screens to look at immune evasion mechanisms across cancer models, showing that IFN-mediated upregulation of classical and non-classical MHC class I inhibitory checkpoints facilitate immune escape.

In a pilot feasibility study involving recipients of allogeneic hematopoietic stem cell transplants, adherence to a dietary intervention and its effects on the gut microbiota were assessed in the run-in to a study testing the effects of modulation of the microbiome on transplant outcomes.

Wolf et al. show that N-Ank proteins combine their curvature-sensing ankyrin repeat array and N-terminal amphipathic helix to shape membranes, and ankycorbin shapes membrane protrusions in developing neurons.

The biogenesis of eukaryotic ribosomes is a multi-step process involving the action of more than 200 different ribosome assembly factors. Here the authors show that Rps20 acts as a conduit to coordinate maturation steps across the head domain of the nascent small ribosomal subunit.

Sensitive radio dishes of the Square Kilometre Array will affect phone reception — and could harm local economies, say farmers.

The epigenomic landscape of renal cell carcinoma (RCC) remains to be explored. Here, integrative epigenomic analysis of primary human RCC samples and RCC GWAS risk SNPs identifies transcription-factor specific subtypes and enrichment of risk variants in allelically-imbalanced peaks.

An apparent redundant role with EZH2 has rendered EZH1 as a secondary player in PRC2-mediated homeostasis regulation. Here, the authors report that gain- and loss-of-function variants in EZH1 cause neurodevelopmental disorders, highlighting its functional relevance.

The lipid kinase PI3KC2α is essential for embryogenesis, yet its role in adult homeostasis is unknown. Here, the authors show that PI3KC2α regulates the structure of the internal membrane reserves of murine megakaryocytes and platelets, affecting the platelets’ adhesiveness and prothrombotic function.

Misfolded Aβ proteins can form proteopathic seeds that drive initiation, progression, and spreading of amyloidosis in the brain. Jucker and colleagues report that Aβ seeds can persist in mouse brain for months in the absence of host-derived Aβ and can then regain propagative and pathogenic activity in the presence of host Aβ.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

A genome-wide association study in large cohorts of patients with different types of cancer treated with immune checkpoint inhibitors identifies genetic variants associated with immune-related adverse events.

Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

Accuracy of free-energy calculations can be improved by constructing an experimental benchmark for solid–solid free-energy differences, quantifying statistical errors for the computed free energies and placing both hydrate and anhydrate crystal structures on the same energy landscape.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

Cardiac progenitor cells (CPCs) form cardiomyocytes, pericytes, smooth muscle and endothelial cells during embryonic development. Here, the authors characterize mouse CPCs marked by Nkx2.5 and Isl1 from E7.5 to E9.5 by single cell RNA-seq and ATAC-seq, showing fate transitions involve distinct open chromatin state.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Benchmarking of scATAC-seq protocols demonstrates the effects of data quality on downstream analyses.