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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.

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.

m⁶A modifications are measured in living cells with a fluorescent reporter.

Kate Meyer reminds us of a study of mRNA N⁶-methyladenosine that predated the epitranscriptomics era by decades.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Blood plasma protein data was combined with machine learning models for a simple method to determine differences in organ-specific aging; the study provides a basis for the prediction of diseases and aging effects using plasma proteomics.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

Getting around the limitations of antibody-based N⁶-methyladenosine (m⁶A) pulldown, such as high input requirements and cross-reactivity, DART-seq profiles transcriptome-wide m⁶A occurrences from RNA amounts equivalent to the RNA obtained from 1,000 cells.

Over half the world’s rivers dry periodically, yet little is known about the biological communities in dry riverbeds. This study examines biodiversity across 84 non-perennial rivers in 19 countries using DNA metabarcoding. It finds that nutrient availability, climate and biotic interactions influence the biodiversity of these dry environments.

Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.

Recent advances in the ability to detect mRNA base modifications have led to a renewed appreciation for the diversity of the epitranscriptome and its ability to influence gene expression. Now, a study in Cell adds acetylated cytidine (ac⁴C) to the list, identifying it as a widespread mark in cellular mRNAs that influences both mRNA stability and translation.

Heterozygous mutateons in the caspase-8 cleavage site of RIPK1 cause a range of autoinflammatory symptoms in humans, and caspase-8 cleavage of RIPK1 in a mouse model limits TNF-induced cell death and inflammation.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

The authors perform the first single-cell profiling of m⁶A in the mouse brain. They uncover relative hypomethylation of microglial mRNA compared to other cell types, and they identify hundreds of RNAs that undergo differential methylation with age.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

Using zooarchaeology, palaeoproteomics, ancient sediment DNA and stable isotope analyses, the authors characterize the ecology of the Homo sapiens individuals associated with the ‘transitional’ Lincombian–Ranisian–Jerzmanowician technocomplex at Ilsenhöhle in Ranis.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

The mTORC1 complex has been implicated in tumorigenesis owing partially to its ability to increase protein translation; now, mTORC1 activity in the mouse intestine is shown not to be required for normal homeostasis but to be necessary for the triggering of tumorigenesis by APC mutations, suggesting that it could be a good target for the prevention of colorectal cancer in high-risk patients.

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.

Genome-wide and multitrait analyses identify novel loci associated with hypertrophic cardiomyopathy and relevant left ventricular traits. Gene-level burden analyses show that rare truncating SVIL variants are associated with high risk of hypertrophic cardiomyopathy.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

N⁶-Methyladenosine (m⁶A) is a post-transcriptional RNA modification that modulates RNA structure through a destabilization of m⁶A base pairing. Here the authors use NMR and UV melting experiments and show that m⁶A can also stabilize m⁶A–U base pairs and global RNA structure when positioned adjacent to a 5ʹ bulge.

Infection with SARS-CoV2 and the development of Coronavirus disease 2019 (COVID-19) has been linked to induction of autoimmunity and autoantibody production. Here the authors characterise the new-onset IgG autoantibody response in hospitalised patients with COVID-19 which they correlate to the magnitude of the SARS-CoV2 response.

Aifantis and colleagues identify the E3 ubiquitin ligase SPOP as a negative regulator of ‘emergency hematopoiesis’ in bone marrow hematopoietic stem progenitor cells.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Previous studies have shown genome-wide associations between polymorphisms in the gene FTO (fat mass and obesity associated) and type 2 diabetes and obesity, and genetic manipulation of Fto in mice causes feeding dysregulation and body weight changes. Here Hess et al. show that FTO affects the activity and function of midbrain dopaminergic neurons and subsequent reward-related behaviors. The study also shows that FTO acts as a demethylating enzyme for specific mRNAs in vivo, including mRNAs in the dopaminergic signaling pathway.

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.

Grailey et al. investigate the impact of different terminologies used to describe AMR, testing terms co-designed with the public. Terminology that is familiar, such as the inclusion of ‘antibiotics’ can significantly increase the understanding of AMR by the public, and impact behavioural intent regarding antibiotic use.

In order for quiescent galaxies to maintain their low-to-non-existent star formation, there must be a mechanism to remove or heat gas that would otherwise cool to form stars; now supermassive black hole winds that are sufficient to suppress star formation in such galaxies are reported.

The results of transcriptome-wideN⁶-methyladenosine (m⁶A) mapping techniques have resolved many of the long-standing concerns regarding the physiological relevance of m⁶A, which suggests that this modification regulates mRNA fate and function. The identification of adenosine methylases and demethylases provides insights into the cellular pathways that involve m⁶A and indicates a role of m⁶A in physiological processes.

Yanick Crow, Sun Hur and colleagues show that gain-of-function mutations in IFIH1 cause a spectrum of neural and immunological phenotypes associated with enhanced interferon signaling. The mutations increase the affinity of IFIH1 for RNA, leading to immune upregulation and inflammatory disease.

Studies of human genetics have been used to identify promising drug targets, and might also inform safety assessment in the drug discovery process. In their Review, Ward and co-authors from industry discuss how genetic studies of rare and complex human diseases can be used to predict potential on- and off-target effects associated with modulating a given target. They also outline suggested best practices for incorporating human genetic data into safety assessments during drug development.