Search

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Emmanuel Mignot and colleagues report that variants in the T-cell receptor alpha (TRA@) locus are strongly associated with narcolepsy. This is the first documented involvement of the TCR locus in human disease and will shed light on how HLA-TCR interactions contribute to organ-specific autoimmune targeting.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

HIV reservoir decay is less well studied in acute infection. Here, the authors show that reservoir decay rates are biphasic and 5x faster in people initiating antiretroviral therapy during acute HIV than prior estimates for chronic HIV. Higher initial CD4+ counts and lower viral loads predicted faster decay.

Emmanuel Mignot and colleagues report genome-wide association analyses identifying a new susceptibility locus for narcolepsy. They identify associated variants in the 3′ untranslated region of P2RY11, a purinergic receptor that modulates immune cell viability.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

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.

The diagnosis of sleep disorders such as narcolepsy and insomnia currently requires experts to interpret sleep recordings (polysomnography). Here, the authors introduce a neural network analysis method for polysomnography that could reduce time spent in sleep clinics and automate narcolepsy diagnosis.

Resonant magnetic excitations are common in unconventional superconductors, but the mechanism for their formation is elusive. Using inelastic neutron scattering, this study finds similar excitations in the non-superconducting heavy-fermion metal CeB₆, suggesting common behaviour between the two ground states.

Discovering disease genes on the X chromosome can be particularly challenging. Here, the authors use features of known disease genes and machine learning to predict genes that remain to be associated with disorders on this chromosome.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

The complex life cycle ofMyxococcus xanthusincludes predation, swarming, fruiting-body formation and sporulation. The large genome of this bacterium contains eight chemotaxis gene clusters that define eight two-component chemosensory pathways, most of which have dedicated functions in motility or development.

Primary lymphoedema can lead to the swelling of the extremities and facial dysmorphism. Here the authors present evidence that compound heterozygous and homozygous mutations inPIEZO1result in an autosomal recessive form of generalised lymphatic dysplasia.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Robert Rathbun Wilson — artist, architect, humanitarian and physicist.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Whilst emergent phenomena and potential technological applications in materials may rely of the coupling between spin, lattice, and electronic degrees of freedom, little is known about direct coupling mechanism between spins and phonons. Here, the authors evidence such behaviour in noncentrosymmetrc FeSi.

Katsushi Tokunaga and colleagues report the results of a genome-wide association study for narcolepsy. A variant on chromosome 22 between CPT1B and CHKB is associated with increased risk of the disorder. Both gene products have previously been linked to the physiology of sleep, making each a potential susceptibility factor.

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.

The unconventional behaviour of samarium hexaboride has been difficult to explain in part because of differences between samples. Here the authors use gadolinium to exemplify that hard to avoid impurities introduce a low energy density of states that may explain earlier observations.

Phagocytosis is a typically eukaryotic feature that could be behind the origin of eukaryotic cells. Here, the authors describe a bacterium that can engulf other bacteria and small eukaryotic cells through a phagocytosis-like mechanism.

Fgf17 in young CSF boosts oligodendrocyte progenitor cell proliferation and differentiation in the aged hippocampus, improving memory function.

Ewing sarcoma (EWS) is a rare pediatric bone cancer typically involving the EWSR1-FLI1 fusion. Here the authors perform a genome-wide association study and report three new EWS risk loci that reside near GGAA repeat sequences, and identify candidate genes (RREB1 and KIZ) from eQTL analysis.

Although imatinib gives good clinical results in chronic myeloid leukaemia (CML), residual disease attributed to quiescent CML stem cells remains in many patients; here glitazones are shown to reduce the pool of CML stem cells and achieve lasting disease eradication in CML patients in combination with imatinib.

Cell segmentation is crucial in many image analysis pipelines. This analysis compares many tools on a multimodal cell segmentation benchmark. A Transformer-based model performed best in terms of performance and general applicability.

A comparative analysis of methods for scoring human sleep data, in particular sleep spindles, from encephalographic recordings is reported. The authors develop methods for crowdsourcing the identification of sleep spindles and compare the detection performance of experts, non-experts and automated algorithms.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

This article reviews growing evidence suggesting that narcolepsy, a chronic sleep disorder caused by deficiency of hypocretin (also known as orexin), has an immune-mediated basis, explores the potential role of autoreactive lymphocytes in the disease process, and proposes future research directions to elucidate its pathogenesis.