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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.

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.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

A high-throughput chemical–genetic screening approach for the discovery of targets and chemicals to treat Mycobacterium tuberculosis yields tenfold more hit compounds than conventional whole-cell screening methods.

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.

A screen utilizing an environmental DNA library in Escherichia coli is used to identify Brig1, a previously unknown anti-phage defence system with homologues across distinct clades of bacteria.

Aerobic glycolysis is a hallmark of fast-growing cells, but it is unclear whether glycolysis was selected for its speed. Glycolysis produces ATP slower than respiration (per protein mass) and is beneficial for rendering cells robust to hypoxia.

Using a cryogenic 300-mm wafer prober, a new approach for the testing of hundreds of industry-manufactured spin qubit devices at 1.6 K provides high-volume data on performance, allowing optimization of the complementary metal–oxide–semiconductor (CMOS)-compatible fabrication process.

Direct observation of G-quadruplexes (G4s) in live cells is challenging. Here the authors report a method to identify G4s within the nuclei of live and fixed cells using a fluorescent probe combined with fluorescence lifetime imaging microscopy.

How GABAergic interneurons regulate segregation and integration among pyramidal cells to separate brain networks remains unclear. In this study, the authors show that subsets of chandelier cells in prelimbic area mediate directional inhibitory control of both local pyramidal neuron ensembles and global cortical subnetworks.

Spatial working memory is known to involve the prefrontal cortex and the hippocampus, but the specificities of the connection have been unclear; now, a direct path between these two areas is defined that is necessary for the encoding of spatial cues in mice, but is not required for the maintenance or retrieval of these cues.

Dedifferentiated liposarcomas (DDLPS) typically have dedifferentiated (DD) and well-differentiated (WD) components, although their cellular origins remain elusive. Here, the authors characterise primary DDLPS tumours using bulk and single-cell multi-omics and find adipocyte stem cells that could be a common ancestor of WD and DD components.

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.

Bacterial CRISPR–Cas loci acquire short phage sequences called spacers that integrate between DNA repeats and how these viral sequences are chosen was unknown; in these studies of the type II CRISPR–Cas system of Streptococcus pyogenes, the Cas9 nuclease known to inactivate invading viral DNA was found to be required for the selection of functional spacers during CRISPR immunity.

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.

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.

Whole-genome analysis of oestrogen-receptor-positive tumours in patients treated with aromatase inhibitors show that distinct phenotypes are associated with specific patterns of somatic mutations; however, most recurrent mutations are relatively infrequent so prospective clinical trials will require comprehensive sequencing and large study populations.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

A combination of genetic strategies and tools is used to define and fate-map different subtypes of glutamatergic pyramidal neurons according to their developmental and molecular programs, providing insight into the assembly of cortical processing networks.

Humans can infer rules for building words in a new language from a handful of examples, and linguists also can infer language patterns across related languages. Here, the authors provide an algorithm which models these grammatical abilities by synthesizing human-understandable programs for building words.

Hailong, an anti-phage defence system, synthesizes an oligodeoxyadenylate signal that blocks effector activity in the absence of phage infection but is degraded by phage-encoded DNA exonucleases, leading to protective growth arrest of infected cells.

Cyclic peptides are of particular interest due to their pharmacological properties, but their design for binding to a target protein is challenging. Here, the authors present a computational “anchor extension” methodology for de novo design of cyclic peptides that bind to the target protein with high affinity, and validate the approach by developing cyclic peptides that inhibit histone deacetylases 2 and 6.

Observations of TOI-849b reveal a radius smaller than Neptune’s but a large mass of about 40 Earth masses, indicating that the planet is the remnant core of a gas giant.

The enzyme uracil DNA glycosylase does not actively extrude just the uracil base from the DNA helix to facilitate its removal; instead, transient, passive opening of thymine: adenine and uracil: adenine base pairs allows both thymine and uracil to become extrahelical, but only uracil can subsequently fit in the active site.

Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic disease that leads to renal failure. Here Hajarniset al. show that miR-17 modulates cyst progression in ADPKD through metabolic reprogramming of mitochondria and its inhibition slows cyst development and improves renal functions.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.

During early platelet spreading a novel F-actin structure forms, called the actin nodule. Here Poulter et al.demonstrate that actin nodule formation depends on WASp and the Arp2/3 complex, and using super-resolution microscopy they show that nodules bear a structural resemblance to podosomes.

Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.

A multi-ancestry transcriptome-wide association study using an optimal linear combination of association statistics provides insights into tobacco use biology and suggests opportunities for drug repurposing.

A conserved network of bacteria and fungi underpins cadaver decomposition despite selection effects of location, climate and season.

Genomic studies of canine tumours have been done for individual cancer types or dog breeds. Here the authors analyse canine tumour genomics data across multiple breeds and cancer types, finding that mutational burden is associated with TP53 mutations and that Golden Retrievers are enriched for particular signatures.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

Deficiency in Gnas, encoding the Gs protein α subunit, is sufficient to induce medulloblastoma in mice due to derepression of the Sonic hedgehog pathway.

GRB 060505 and GRB 060614 were not accompanied by supernova emission down to limits hundreds of times fainter than the archetypal SN 1998bw that accompanied GRB 980425, and fainter than any type Ic supernova ever observed.

The sequencing of AML genomes of eight patients before and after relapse reveals two major patterns of clonal evolution, with chemotherapy appearing to have a role in both patterns.

The tight confinement of polaritons in 2D materials leads to increased optical losses. Here, the authors demonstrate image phonon polariton modes in hexagonal boron nitride with an antisymmetric charge distribution that feature quality factors of up to 501 and an effective index of 132.

The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) aims to better understand population genetics of the African diaspora. Here, it uses deeply sequenced whole-genomes to describe the impact of admixture and potential disease burden of deleterious variants.

Red and yellow versions of the genetically encoded dopamine sensor dLight1 have been developed and allow multiplexed imaging of dopamine with neurotransmitter or cell-type-specific calcium combined with green sensors or actuators, as demonstrated ex vivo and in behaving rodents.

The response to respiratory virus exposure can currently not be predicted by pre- or early post-exposure molecular signatures. Here, the authors conduct a community-based analysis of blood gene expression from healthy individuals exposed to respiratory viruses and provide predictive models and biological insight into the physiological response.

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

Structural analysis of the uridyl transferases TUT4 and TUT7 reveals the use of two functional modules in the switch from monouridylation of pre-let-7, which promotes let-7 expression, to oligouridylation of pre-let-7, which marks it for degradation.