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MSK-IMPACT is a clinical sequencing platform able to detect genomic mutations, copy number alterations and structural variants in a panel of cancer-related genes. This assay is implemented prospectively to inform patient enrollment in genomically matched clinical trials at Memorial Sloan Kettering Cancer Center (MSKCC). Sequencing results of tumor and matched normal tissue from a cohort of >10,000 patients with detailed clinical annotation provide an overview of the genomic landscape of advanced solid cancers and bring new insights into molecularly guided cancer therapy.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

A spatial transcriptomic analysis of healthy kidneys and those from individuals with chronic kidney disease characterizes the fibrotic microenvironment and highlights features that could be used to predict prognosis.

Using genome-wide meta-analyses of clinical measures of depression and biobank data, the authors investigate symptom-specific genetic associations between depression and subsequent risk for Alzheimer’s disease, finding an absence of a putative genetic overlap between disorders.

The intracellular domain (ICD) of Cys-loop receptors mediates many of their functions, but no complete structure of a Cys-loop receptor ICD is available to date. Here, the authors combine NMR and ESR spectroscopy to determine the full-length ICD structures of the human α7 nicotinic acetylcholine receptor (α7nAChR).

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

The authors employ a semi-empirical method to fit published battery capacity-rate data to extract the characteristic time associated with charge/discharge. These characteristic times are consistent with a physical model that can be used to link rate performance to the physical properties of electrodes.

Brain-machine interfaces are hindered by neuroinflammation. Here, the authors found that bacterial sequences invade the brain post-microelectrode implantation. Antibiotic-treated mice showed reduced bacterial presence and altered neuroinflammatory profile, temporarily improving recording performance.

The synaptic vesicle protein 2 family are essential membrane proteins found in the brain that bind synaptotagmin and are targeted by anti-seizure medications. Structures reveal common features found in transport proteins, and the basis of ligand binding and selectivity.

The genetic basis of tinnitus and how it relates to hearing loss genetics is unknown. In a large GWAS for tinnitus, the authors discover tinnitus’ distinct genetic architecture from hearing loss and its correlation with a spectrum of psychiatric disorders.

Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9).

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

In a cohort of 281 children with diagnosed or suspected cancer presenting to the NHS, implementing routine whole-genome sequencing provided clinical benefit in 29% of cases and led to change in management in 7% of patients.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Betaglycan is a co-receptor for selective TGF-β family ligands. Here, the authors solve its structure in complex with TGF-β and the signaling receptors, which explains its ligand selectivity and reveals its mechanism in potentiating TGF-β signaling.

Panuski et al. demonstrate a programmable photonic crystal cavity array, enabling the spatiotemporal control of a 64 resonator, two-dimensional spatial light modulator with nanosecond- and femtojoule-order switching.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

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.

A defect-engineering strategy exploiting dithiolated molecules enables the formation of covalently interconnected networks based on solution-processed transition metal disulfides, leading to devices with enhanced electrical performance and improved characteristics.

Although epigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, previous studies have been limited in sample size and brain region used. Here, the authors combine data from six DNA methylomic studies of Alzheimer’s disease (N = 1453 unique individuals) to identify differentially methylated loci across cortex.

Methods to achieve large-scale production of defect-free graphene are needed to enable the commercial development of graphene-based devices. It is now shown that high-shear mixing is an effective way to exfoliate graphene and other two-dimensional materials in liquid volumes up to hundreds of litres.

Uterine muscle contracts rhythmically during labour but the underlying electrophysiological mechanisms are not fully understood. The authors of this study show that hERG1 potassium channels reduce human uterine contractions in pregnancy and are suppressed during labour in lean but not in obese women.

Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.

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.

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.

Virus-specific antibody levels after a single dose of the BNT162b2 vaccine in individuals previously infected with SARS-CoV-2 are similar to levels after two doses of the vaccine in infection-naive individuals.

Printing functional inks is attractive for applications in electrochemical energy storage and smart electronics, among others. Here the authors report highly concentrated, additive-free, aqueous and organic MXene-based inks that can be used for high-resolution extrusion and inkjet printing.

While thicker battery electrodes are in high demand to maximize energy density, mechanical instability is a major hurdle in their fabrication. Here the authors report that segregated carbon nanotube networks enable thick, high-capacity electrodes for a range of materials including Si and NMC.

Liquid phase exfoliation is frequently used to produce 2D nanosheets from layered materials, but determining sheet thickness in situhas not been possible. Here, the authors report a spectroscopic technique capable of determining sheet thickness, sheet lengths and concentrations directly from dispersions.

While phosphorene is an exciting new 2D material, techniques to produce it in large quantities in a stable, processable form are lacking. Here, the authors achieve this using liquid phase exfoliation and demonstrate the resultant nanosheets to be useful in a number of applications.

Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

The X-ray structures of engineered variants of the human serotonin transporter show that the antidepressants sertraline, fluvoxamine and paroxetine occupy the central substrate-binding site and stabilize the transporter in an outward-open conformation.

Integrated species distribution modeling across monitoring types, spatial scales, and seasons resolves asynchrony in population trends for an imperiled bat species (Perimyotis subflavus) and strengthens evidence of declines linked to wildlife disease.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

The UK Biobank provides data for three depression-related phenotypes. Here, Howard et al. perform a genome-association study for broad depression, probable major depressive disorder (MDD) and hospital record-coded MDD in up to 322,580 UK Biobank participants which highlights excitatory synaptic pathways.

Cell lines are central to cancer research, but knowing which cell lines are the best representative of actual tumours is a major challenge. Here the authors provide a resource assessment of 65 renal cell lines to assist researchers in selecting suitable lines for studying specific renal carcinoma subtypes.

Developments in medical imaging have driven advances in minimally invasive surgery, and image-guidance is now an integral part of many urological procedures. This Review discusses developments in imaging technologies such as fluoroscopic imaging, molecular imaging, image fusion and four-dimensional ultrasonography, and their applications in urological practice.

A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

A computational approach to generate reference-free protein families from the sequence space in metagenomes reveals an enormously diverse functional space.

Cryo-electron microscopy reveals three conformations of the serotonin transporter in complex with ibogaine, detailing the structural rearrangements that occur between the different stages of its transport cycle.