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This work describes inCITE-seq that jointly measures intranuclear protein levels and the transcriptome in single nuclei, which is applied to mouse brain tissue to relate quantitative protein levels of TFs to gene expression programs.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

This protocol describes a cross-linking mass spectrometry (XL-MS) approach to studying homodimer interfaces, and provides procedures for stable isotope–labeling of one of the two monomers, homodimer refolding, XL-MS, and data analysis.

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.

Pagano and colleagues find that Plk1 and the E3 ubiquitin ligase SCF^βTrCP mediate degradation of the centrosome cohesion protein Cep68 and show this mediates removal of Cep215 from the PCM and subsequent centriole separation in late mitosis.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

Dosage compensation (DC) on the X chromosome has predictable effects on genetic and phenotypic trait variance. Here, the authors use information for 20 quantitative traits in the UK Biobank and across-tissue gene expression to compare X-linked heritability and the effects of trait-associated SNPs between the sexes.

Magnetically intercalated transition metal dichalcogenides provide a platform to study the interplay of magnetism, electronic band structures, and correlations. Here the authors demonstrate a nearly magnetization-free anomalous Hall effect, collinear antiferromagnetism and non-Fermi liquid behavior in V_1/3NbS₂.

SBayesRC integrates genome-wide association summary statistics with functional annotations to improve polygenic prediction of complex traits. Functional partitioning highlights a major contribution of evolutionarily constrained regions to prediction accuracy.

Using a combined before–after control–impact approach shows that existing studies using either before–after or control–intervention methods incorrectly estimate the effectiveness of protected areas in maintaining waterbird populations.

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

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Current first-line treatments of pediatric UC maintain a 6-month remission in only half of the patients. Here, applying multi-omics on intestinal biopsies from treatment-naïve children, the authors show that relapse-prediction using separate omics data is outperformed by a robust machine learning approach combining microbiomes and epigenomes.

Wise management is critical to sustaining fisheries. This study finds that rebuilding plans, ratification of international agreements and harvest control rules yield strong benefits and that these are cumulative.

Climate change strongly impacts regions in high latitudes and altitudes that store high amounts of carbon in yet frozen ground. Here the authors show that the consequence of these changes is global warming of permafrost at depths greater than 10 m in the Northern Hemisphere, in mountains, and in Antarctica.

The ability to infer quantitative kinetic information from single-molecule FRET (smFRET) data can be challenging. Here the authors perform a blind benchmark study assessing different analysis tools used to infer kinetic rate constants from smFRET trajectories, testing on simulated and experimental data.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

A non-canonical tricarboxylic acid cycle is required for changes in cell state.

Jungnickel, Guelle et al. use metabolomics, electrophysiology and cryo-EM approaches to show that MFSD1 is a lysosomal dipeptide uniporter, which provides an additional route to recycle lysosomal proteolysis products to lysosomal amino acid exporters.

In this paper, the authors present findings demonstrating that variations of the MET gene are associated with specific structural differences in key language regions in individuals with schizophrenia.

Julia Zeitlinger, Alexander Stark and colleagues report genome-wide binding profiles for the transcription factor Twist across six Drosophila species. They find that the binding pattern is highly conserved across species, suggesting strong functional constraints at the enhancers that Twist regulates.

ESCRT filaments drive the final abscission between two daughter cells but how they physically interact with the membrane is unclear. Using proteomics, the authors show that syndecan-4/syntenin/ALIX couples the ESCRT machinery to the abscission site and thus promotes efficient abscission.

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.

When studying nematic ordering of cells in a monolayer, it is commonly assumed that the principal stress and cell shape axes are tightly coupled. Here, the authors measure cell shape and cell-generated contractile stresses and show that cells in monolayers form correlated, dynamic domains in which the stresses are systematically misaligned with the cell bodies.

ARPC1B is a component of the actin-related protein 2/3 complex (Arp2/3), which is required for actin filament branching. Kahret al. show that ARPC1B deficiency in humans is associated with severe multisystem disease that includes platelet abnormalities, eosinophilia, eczema and other indicators of immune disease.

Numerous disease-associated variants have been described in GWAS for atrial fibrillation. Here the authors integrate omics data to investigate the consequences of genetic variants for transcript and protein levels in the atrium of the human heart. With this multi-omics approach, authors reveal the regulatory network underlying atrial fibrillation and provide a resource for cardiac gene prioritization.

Medulloblastomas (MBs) are highly heterogeneous paediatric brain tumours that remain challenging to treat. Here, the authors integrate proteomics, epigenomics, transcriptomics and post-translational modification analyses to find molecular subgroups and potential therapeutic targets in MB tumours.

MultiMatch performs geometry-informed colocalization analysis for multi-color microscopy based on multi-marginal optimal unbalanced transport methodology.

The application of partitioned polygenic scores to data from cohorts of patients identifies two distinct subtypes of MASLD with different cardiometabolic risk profiles.

ALS and FTLD are both characterized by insoluble cytoplasmic depositions of TDP43. Here the authors show that the nucleopore protein NUP62 is mislocalized in C9orf72 and sporadic ALS/FTLD and propose that it interacts with TDP-43 to promote its insolubility.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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.

Improving inference in large-scale genetic data linked to electronic medical record data requires the development of novel computationally efficient regression methods. Here, the authors develop a Bayesian approach for association analyses to improve SNP-heritability estimation, discovery, fine-mapping and genomic prediction.

The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. Here, the authors evaluate the relative effectiveness of two major vaccine delivery strategies, namely routine immunization and supplementary immunization activities in five study countries.

Dynamic nanodomains in lead halide perovskites, dictated by A-site cations, crucially affect the optoelectronic properties by modulating electronic disorder and consequently enabling better solar cells and optoelectronic devices.

Peesh et al. show that ischemic stroke reduces microbiota-derived and increases host-derived aryl (AHR) hydrocarbon ligands. Post-stroke treatment with indole-based AHR ligands improved microglia-mediated antigen processing and co-stimulatory immune functions.

The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.

Contact patterns influence the spread of infectious diseases, but mathematical models of epidemics typically only account for age differences in contacts. Here, the authors investigate the importance of other sociodemographic characteristics in shaping contact patterns and vaccine uptake using survey data from Hungary.

Light-oxygen-voltage (LOV) photoreceptors perceive blue light to elicit spatio-temporally defined cellular responses, and their signalling process has been extensively characterized. Here the authors report that the light signal is still transduced in the absence of a conserved Gln residue, thought to be key.

Land management impacts ecosystem functions. Here, the authors conduct field experiments in Germany assessing ecosystem variables in cropland and grasslands showing that sustainable agricultural practices enhance ecological and economic benefits.

Analysis of chromatin accessibility and expression quantitative trait loci in stimulated or naïve macrophages identifies loci that constitutively alter chromatin but affect expression only after stimulation, thus indicating an effect on enhancer priming.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

The authors report that tensile strain applied to CsV₃Sb₅ strongly suppresses the charge-density-wave (CDW) gap, increases the mass of the fermions at the higher-order van Hove singularity (HO-VHS) and drives the energy of the HO-VHS towards the Fermi energy. Further, they suggest an important role of the HO-VHS in superconducting pairing.

Strongly positive phases of the North Atlantic Oscillation increased the persistence of weather events in northwest Europe between 1950-1980 and 1990-2020, amplifying the risk of persistent precipitation and flooding, according to a statistical modeling framework.

Analysis of the imprinted KLF14 locus shows that the type 2 diabetes risk alleles in this region act in adipocytes to reduce KLF14 expression and modulate the expression of almost 400 genes in trans, leading to a shift in body-fat distribution and insulin resistance specifically in females.

Here, Riva et al. employ a multi-modal approach to identify gut microbes stimulated by the popular dietary supplement inulin and reveal that inulin binding and metabolic stimulation are widespread in the microbiome, making the framework a suitable way to study key microbes that perform specific functions in the microbiome.