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It is unclear if rates of autism and other neurodevelopmental and psychiatric diagnoses are elevated in transgender and gender-diverse individuals compared to cisgender individuals. Here, the authors use data from five different large-scale datasets to identify elevated rates of autism diagnoses, diagnoses of other neurodevelopmental and psychiatric conditions, and elevated traits related to autism in transgender and gender-diverse individuals, compared to cisgender individuals.

Insect vectors of diseases locate their animal hosts through olfaction via largely unknown molecular processes. Here the 'empty neuron' system of genetically engineered Drosophila is used to assign specific odorants to the entire repertoire of olfactory receptors of the malaria vector Anopheles gambiae. The results illuminate ecological and neurobiological differences between mosquitoes and fruitflies and provide new potential molecular targets to boost the struggle against insect–borne diseases.

The pannexin 1 channel on the plasma membrane of apoptotic cells mediates the release of find-me molecular signals to attract phagocytic cells for clearance of the apoptotic cells; here the quinolone antibiotic trovafloxacin is identified as a direct inhibitor of pannexin 1, which results in dysregulated fragmentation of apoptotic cells and may partly explain quinolone toxicity.

Cancer cells have altered lipid metabolism. Here the authors show that DAXX promotes lipogenesis and tumorigenesis through interaction with SREBP1/2.

Resident microbiota contribute to HIV and EBV infection in a germ-free humanized mouse model.

Changes in Psoriasis and other inflammatory skin diseases during severity stages can be investigated using single cell and spatial transcriptomics. Here the authors compare different inflammatory skin diseases to emphasise differences in immune cells and inflammatory markers particularly keratinocytes and fibroblasts.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Cross-neutralization assays of early variants and the 501Y.V2 variant of SARS-CoV-2 show that plasma from individuals infected with 501Y.V2 effectively neutralizes all variants, indicating that a vaccine that targets 501Y.V2 may also be effective against other SARS-CoV-2 variants.

Matrix stiffening is a quintessential feature of aged tissues. Authors show that an aged (stiff) matrix epigenetically represses the gene encoding the longevity factor, α-Klotho, resulting in chondrocyte dysfunction, a leading cause of osteoarthritis.

Accurate forecasting of tropical precipitation is dependent on our understanding of the hydrological cycle. Here, the authors present a speleothem-derived record of Mesoamerican precipitation variability since the 1930s, and show that multi-decadal declines in rainfall coincide with major volcanic eruptions.

Naturally occurring genetic variation between inbred mouse strains is used as a mutagenesis strategy to investigate mechanisms responsible for the selection and function of cis-regulatory elements in macrophages; lineage-determining transcription factors are proposed to select enhancer-like regions in the genome in a collaborative fashion and facilitate the binding of signal-dependent factors.

The lysosomal storage disease mucopolysaccharidosis I is treated with recombinant α-L-iduronidase but production of the enzyme is expensive. In this study, α-L-iduronidase is compartmentalized within the endosperm of maize via a unique mRNA strategy yielding the active, correctly glycosylated protein.

Non-alcoholic fatty liver disease (NAFLD) is characterized by increased hepatic triglyceride content (HTGC) in the absence of high alcohol consumption. Here the authors show that a genetic variant in TM6SF2, which is known to be associated with HTGC, is a clinically relevant modifier of hepatic fibrogenesis and increases the risk of progressive NAFLD.

The generation of a sustainable supply of erythroid progenitors is essential for the reliable production of anin vitroderived red blood cell clinical product. Here the authors immortalize early human erythroblasts to generate the first cell line capable of differentiation into functional adult reticulocytes.

Pore-forming toxins act by forming oligomeric pores in lipid membranes. Here the authors report the crystal structure of the lysenin pore, providing insights into the assembly and function of the pore in addition to suggesting that its properties make lysenin potentially well-suited for nanopore sensing applications.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Dynamic redundancy by horizontal gene transfer stabilizes gene abundances amidst compositional fluctuations in microbial communities, which suggests a means to program gene stability of complex microbiota.

Genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2 identify mucins as key host factors restricting viral infection.

PDB-Dev hosts integrative structural models of biomolecular assemblies solved by hybrid methods.

This paper identified >500 genetic loci associated with behaviors and disorders related to self-regulation, including addiction and child behavior problems. The resulting genetic risk scores predict several behavioral, medical and social outcomes.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease. Here the authors characterize diverse genetic alterations in MIBC that convergently lead to constitutive activation of PPARgamma/RXRalpha and result in immunosurveillance escape by inhibiting CD8+ T-cell recruitment.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Proteome thermal stability is probed using limited proteolysis and mass spectrometry.

Protein structure changes can be charted on a global scale with a method that couples limited proteolysis with mass spectrometry–based proteomics.

Marker-based CRISPR screens in pancreatic cancer cells followed by functional validation highlight a role for MED12 in bridging ΔNp63 and components of the Mediator family. This interaction helps drive basal cell identity in pancreatic ductal adenocarcinoma.

An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

This study reports and characterizes the impact of loss-of-function GDF15 variants in human individuals.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

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.

A new discovery strategy, ‘reverse metabolomics’, facilitates high-throughput matching of mass spectrometry spectra in public untargeted metabolomics datasets, and a proof-of-concept experiment identified an association between microbial bile amidates and inflammatory bowel disease.

Women with germline variants in BRCA genes are predisposed to ovarian cancer. In this study, the authors demonstrate that fimbrial tissue from the ovary, the site of ovarian cancer, in BRCAmutant carriers contains marked DNA methylation changes compared with the proximal region of the ovary.

Iron is essential during pregnancy for embryo and placental development and maternal health. However, in this study using mouse models, the authors demonstrate that excess maternal iron causes adverse embryo outcomes in pregnancies with underlying systemic inflammation.

A clinical study shows that immunotherapy with anti-HIV-1 antibodies maintains prolonged viral suppression after anti-retroviral treatment is discontinued and affects the size and composition of the intact but not the defective proviral reservoir.

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.

The authors report 1.3 mm observations of dust emission from strongly lensed galaxies where star formation is quenched, demonstrating that gas depletion is responsible for the cessation of star formation in some high-redshift galaxies.

DNA supercoiling can result in underwinding with negative supercoiling or overwinding with positive supercoiling of the DNA double helix. Here the authors reveal insights into the dynamic relationship between DNA supercoiling-induced sequence-dependent disruptions to base pairing, DNA looping, and the shape of the DNA molecule.

It is thought that polyphenols inhibit organic matter decomposition in soils devoid of oxygen. Here the authors use metabolomics and genome-resolved metaproteomics to provide experimental evidence of polyphenol biodegradation and maintained soil microbial community metabolism despite anoxia.

Agnihotri and colleagues show that loss of the MAT2A enzyme of the methionine cycle induces a global depletion of H3K36me3 and extends survival in glioma models, representing a potential therapeutic vulnerability.

The ability to measure the metabolome on a global scale lags behind other omics techniques.

The combination of anti-GD2 and CD47 blockade mediates robust anti-tumor activity in mouse models of neuroblastoma, osteosarcoma and small-cell lung cancer by reorienting macrophage activity toward tumor cell phagocytosis.