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Nir Hacohen, Bruce Walker, David Sabatini, Eric Lander and colleagues perform a CRISPR–Cas9-based screen for host factors that are required for HIV infection. They identify two known and three novel factors that are necessary for viral infection but that are not required for cell viability, making them potential targets for antiviral therapy.

Here, Dirk Lefeber and colleagues identify functional mutations in ATP6AP1 encoding Ac45. The authors show that Ac45 is the functional ortholog of yeast V-ATPase assembly factor Voa1 and provide evidence for tissue-specific Ac45 processing, associated with the clinical phenotype of immunodeficiency, hepatopathy, and neurocognitive abnormalities.

Gene editing induces paternal haploid plants in hexaploid wheat.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

Cellular nuisance compounds are a burden in chemical biology and drug screening. Here the authors profile prototypical cytotoxic and nuisance compounds using the cell painting assay to systematically characterise cellular morphologies associated with compound-dependent cellular injury and nuisance activity.

Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.

The approximately 5-Gb tuatara (Sphenodon punctatus) genome assembly provides a resource for analysing amniote evolution, and highlights the imperative for meaningful cultural engagement with Indigenous communities in genome-sequencing endeavours.

A newly developed genetically engineered mouse model enables the analysis of specific antigen presentation in vivo, providing insights into the tumour immunopeptidome and cancer progression.

Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement.

Thlaspi arvense (pennycress) has the potential to provide new sources of food and bioproducts when grown as a winter cover crop. Here, Chopra et al. demonstrate that multiple desirable traits can be stacked to rapidly domesticate pennycress. The resulting crop integrates into current crop rotations and produces seeds with improved nutritional qualities, easier harvesting and suitability for human consumption.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Using transcriptomic data from human brain cells, the authors show that the expression patterns of the genes implicated in human cognition and brain evolution overlap in specific neuron types, and relate to cellular function and structure.

Chemical inducer of dimerization (CID) modules can be used to effectively control biological processes; however, CID modules have been explored primarily in engineering cells for in vitro applications using inducers that have limited clinical utility. Here, the authors identify a CID module with favorable properties to enable rapid translation from in vitro applications to potential use in humans.

An (ultraviolet) dust attenuation feature at 2,175 Å, attributed to carbonaceous dust grains in the Milky Way and nearby galaxies, also exists in galaxies up to a redshift of 7.

Kilonovae observations can be used to out constraints on the Hubble constant (H0). Here, the authors show H0 measurements by combining light curves of four short gamma-ray burts with GW170817 are about a factor of 2-3 more precise than the standard-siren measurements using only gravitational-waves.

The dissociation mechanism of the heme axial ligand in heme proteins is not yet fully understood. The authors investigate the photodissociation dynamics of the bond between heme Fe and methionine S in ferrous cytochrome c using femtosecond time-resolved X-ray solution scattering and X-ray emission spectroscopy, simultaneously tracking electronic and nuclear structure changes.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

Size and shape of the brain are, among others, influenced by the dimensions of the skull. Here, the authors report genome-wide association studies for head circumference and intracranial volume in children and adults and the identification of nine common or low-frequency variants associated with these traits.

AI language modelling and generation approaches have developed fast in the last decade, opening promising new directions in human–AI collaboration. An AI-in-the loop conversational system called HAILEY is developed to empower peer supporters in providing empathic responses to mental health support seekers.

Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Protein methyltransferase PRMT5 symmetrically dimethylates arginine residues in proteins, including histones, and has been associated with tumorigenesis. The identification of EPZ015666 as a potent chemical probe of PRMT5 could promote understanding of the role of PRMT5 in human disease both in cells and in vivo.

Accumulation of interseismic strain may now be constrained by satellite observations. Here, the authors show that strain accumulation rates on the North Anatolian Fault are constant for the interseismic period indicating that lower-crustal viscosities from postseismic studies are not representative.

A transiting planet with a period of about 8.5 days and a radius 0.4 times that of Jupiter is reported within the debris disk around the star AU Microscopii.

Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

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.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Current bone fracture repair options include metallic and resorbable systems, both of which suffer from various issues and limitations. Here, the authors demonstrate resorbable and biocompatible silk bone screws, via in vivotesting.

Rosalind Eeles and colleagues report meta-analysis of genome-wide association studies for prostate cancer and genotyping on the custom iCOGS array in 25,074 cases and 24,272 controls from 32 studies available in the PRACTICAL Consortium. They identify 23 new prostate cancer susceptibility loci, 20 of which are associated with both aggressive and non-aggressive disease.

Two high-quality genomes of petunia wild parents reveal two rounds of hexaploidization in the evolution of Petunia lineage and provide insights into the diversity of floral patterns and pollination systems — enhancing the model value of this genus.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.

A novel variant annotation metric that quantifies the level of expression of genetic variants across tissues is validated in the Genome Aggregation Database (gnomAD) and is shown to improve rare variant interpretation.

The authors show that an out-of-plane antidamping spin–orbit torque can produce a sizeable change in the switching dynamics of a magnetic layer with perpendicular anisotropy.

Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.

Cortical thickness is asymmetric, and cortical thinning occurs with age and in disease. Here the authors investigate if both cortices thin at the same rate or if the thicker hemisphere declines faster in aging and in Alzheimer’s disease.

A machine learning approach is presented to identify dominant patterns in disease progression in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. The nonlinearity of ALS progression has important clinical implications.

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 authors examined the differential roles of GluN2A and GluN2B in modulating synaptic plasticity and behavior. This study provides insight into how gene duplication events during evolution can produce new functional consequences.

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.