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Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.

Toxicities limit combination of PARP inhibitors (PARPi) and chemotherapy in patients with germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) breast cancer. Here, the authors report a preclinical study followed by a randomised phase II/III clinical trial investigating the addition of a gap between chemotherapy (carboplatin and paclitaxel) and PARPi (olaparib), in patients with early gBRCAm breast cancer.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

Few aerobic hyperthermophilic microorganisms are known to degrade polysaccharides. Here, Nou et al. use genomic information to enrich and optical tweezers to isolate an aerobic hyperthermophilic bacterium that can grow at 65–87.5 °C using polysaccharides as sole carbon sources.

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.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Integration of genome-wide association analysis of 406,504 individuals in the UK Biobank and scATAC–seq data reveals that variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.

Trace metals have been an important ingredient for life throughout Earth’s history. Here, the authors show that a member of an elusive archaeal lineage (Caldarchaeales or Aigarchaeota) requires tungsten for growth, and provide evidence that tungsten-dependent metabolism played a role in the origin and evolution of this lineage.

A stable crystal phase and two metastable liquid phases of the ST2 model of water exist at the same deeply supercooled condition, and the two liquids undergo a first-order liquid–liquid transition that meets stringent thermodynamic criteria.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

A study details the results of the PARTNER trial, a prospective, randomized controlled trial of the use of neoadjuvant olaparib with carboplatin–paclitaxel chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type.

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.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

To overcome mass transport limitations in zeolite-catalysed reactions, scientists must often resort to hierarchical or nanosized zeolites; however, the synthesis of such materials remains challenging. Here the authors disclose a one-pot method for the preparation of Si-zoned MFI-type catalysts with improved diffusion properties for the methanol-to hydrocarbon reaction.

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.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Forest inventory data from the 1980s and 2000s show the response of eastern USA forests to climate variability; direct effects of climate on forest biomass are amplified by changes in tree species composition.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

An analysis based on data from the Global Dietary Database shows mean animal-sourced food intakes among children and adolescents increased modestly from 1990 to two portions per day in 2018, but remain low in sub-Saharan Africa, India and Bangladesh.

Dietary quality is reported at the global, regional and national level across 185 countries. Though diet quality increased modestly since 1990 at the global level, in South Asia and Sub-Saharan Africa it did not improve. In some regions, children’s dietary quality is lower than that of adults.

The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Crystal symmetry is notoriously uncorrelated to the symmetry of the constituent molecules that make up a crystal. Symmetry breaking is typically thought to occur during nucleation and growth, but a symmetry element of olanzapine crystals—an inversion centre—has now been shown to emerge in centrosymmetric dimers extant in solution prior to crystallization.

Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.

Pharmacotyping analyses of large cohorts of pediatric acute lymphoblastic leukemia identify correlations between drug sensitivities and clinical outcomes across different genomic subtypes.

Folkersen et al. report the first results from the SCALLOP consortium, a collaborative framework for pQTL mapping and biomarker analysis of proteins on the Olink platform. A total of 315 primary and 136 secondary pQTLs for 85 circulating cardiovascular proteins from over 30,000 individuals were identified and replicated to yield new insights for translational studies and drug development.