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The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

The latest training techniques emphasize classroom practice and design thinking.

Data from over 2,500 reefs worldwide is used to identify 15 bright spots—sites where reef biomass is significantly higher than expected—and surveys of local experts in these areas suggest that strong sociocultural institutions and high levels of local engagement are among the factors supporting higher fish biomass.

Variants of adeno-associated viruses displaying robust and widespread transduction in murine, porcine and non-human-primate kidneys, and in human kidney organoids, can be obtained via the cross-species cycling of capsid libraries in the different kidney models.

Central nervous system lesions are reduced following focused ultrasound treatment in a mouse model.

Here, the authors use fMRI data to update connectomes with new, asymmetric, and signed weights, leading to an intuitive brain structure that is aligned to functional brain systems, more efficient, subject-specific, state-dependent and varies with age

Base-editing screens of primary T cells reveal genetic variants beneficial to immunotherapies.

An automated perfusable microfluidic bioreactor can generate clinical doses of viable CAR T cells that are functionally comparable to cells produced in standard open-culture systems.

In the final report of a phase 1 trial evaluating intracerebroventricular B7-H3-targeting CAR T cells in children and young adults with diffuse intrinsic pontine glioma, repeated intracranial infusions were feasible and well tolerated with a median overall survival of 19.8 months and 3 patients surviving over 40 months from diagnosis.

‘Manufacturing CAR-T cells is a streamlined and highly regulated procedure involving T-cell-expansion and activation on a standardised platform. Here, the authors show that a personalized approach, taking the phenotypic attributes of individual patients’ T cells into account, leads to more efficient CAR-T cell manufacturing and better CAR-T cell functionality.

Managing herbicide resistance problem needs the identification of new herbicidal modes of action. Here, the authors solve the crystal structures of Arabidopsis HMGR and show HMGR as a potential new herbicide target by identifying plant-specific HMGR inhibitors and engineering tolerant trait in Arabidopsis.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

T cells derived from stem cells can be harnessed for regenerative medicine and cancer immunotherapy, but current technologies limit production and translation. Here, the authors present a serum-free, stromal-cell free DLL4-coated microbead method for the scalable production of T-lineage cells from multiple sources of stem cells.

Exome-wide genetic analysis on >300,000 individuals identifies associations with plasma lipid traits. Loci significantly associated with cholesterol and triglycerides are examined together to determine the effects of alleles on type 2 diabetes and coronary artery disease risk.

By integrating time series analyses of transcripts, lipids and metabolites, the authors show that microorganisms in the open ocean partition scarce resources temporally, with different microbial groups expressing nitrogen uptake and assimilation processes at different points throughout the diel cycle.

Advances in organoid culture have enabled the modelling of many aspects of organs in vitro, transforming experimental biology. This Review provides a comprehensive overview of the current and emerging liver and pancreas organoid technologies and discusses current limitations and future directions.

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.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Bacteria assemble the surface layer (S-layer), a crystalline protein coat surrounding the curved surface, using protein self-assembly. Here authors image native and purified RsaA, the S-layer protein from C. crescentus, and show that protein crystallization alone is sufficient to assemble and maintain the S-layer in vivo.

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.

This paper examines eight individual genomes using a clone-based sequencing approach, for structural variants of 8,000 nucleotides or more. One of the first high-quality inversion maps for the human genome is generated, and it is demonstrated that previous estimates of variation of this sort have been too high.

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.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Published sequencing data sets of cancer samples could be used to identify genetic variants associated with the risk of developing cancer. Here, Luet al. analyse over 4,000 tumour-normal pairs to reveal variable frequencies of inherited susceptibilities across 12 cancer types and find enrichment of functionally validated missense variants of unknown significance.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

The authors present structures of plant polerovirus ^NRTD proteins that protrude from the viral capsid and show that the purified ^NRTD can inhibit insect transmission and act as a bioinsecticide, providing a blueprint for control of related viruses.

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

Circulating proteins are a potential source of cancer biomarkers. Here, the authors assessed 2,074 circulating proteins and used Mendelian randomisation to compare with the risk of 9 common cancer types across multiple GWAS cohorts and identified key considerations with respect to the potential for adverse effects of altering cancer-risk proteins that inform their utility in cancer prevention.

This study shows that a multitrophic community model jointly recapitulates diel rhythms in abundances of Prochlorococcus picocyanobacteria, as well as viral infection, viral abundances and grazer abundances. Model-data integration implies that grazing predominantly controls Prochlorococcus abundances in surface waters of the North Pacific Subtropical Gyre, despite high viral densities.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

Knowledge about the full reaction signature, such as the complete profile of products and side-products is important in accelerating discovery chemistry. Here, the authors report a methodology using high-throughput experimentation and multivariate data analysis to examine Palladium- catalyzed cross-coulpling reactions.

In this work, authors assess airway microbiome dynamics to show bacterial pneumonia in critically ill COVID-19 patients is significantly associated with death, corticosteroid treatment, disruption of the lung microbiome and a distinct pulmonary host response.

The authors develop a supervised and unsupervised learning algorithm Signature. Machine learning and network model analysis of Hi-C datasets across 62 2n genomes suggest that inter-chromosomal contacts demarcate genome topology along a spatial gradient of genome activity.

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.

Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

An ultra-high-throughput multiplex protein–DNA binding assay is used to assess binding of 270 human transcription factors to 95,886 noncoding variants in the human genome, providing data to improve prediction of the effects of noncoding variants on transcription factor binding and thereby increase understanding of molecular pathways involved in diverse human traits and genetic diseases.

An analysis of GPS pedestrian traces shows that (1) people increasingly deviate from the shortest path when the distance between origin and destination increases and that (2) chosen paths are statistically different when origin and destination are swapped. Ultimately, this can explain the observed human attitude in selecting different paths upon return trips.

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.