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CORAL can infer the occurrence of rare species based on common species, using DNA metabarcoding data or other high-dimensional biodiversity data. The approach is illustrated on a large-scale biodiversity survey from Madagascar.

Although the trivalent actinides are similar to the lanthanide series in terms of chemistry and bonding, their structures and properties can diverge significantly. Here, the authors report a series of complexes of the trivalent actinides Np(III) through Cf(III) along with their lanthanide counterparts using a polarizable non-innocent, sulfur-donor ligand.

Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

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.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

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

Next generation precision lysine-specific histone demethylase 1A (LSD1) covalent inhibitors which selectively block LSD1 enzyme activity by forming a compact N-formyl-FAD adduct have been developed, but the mechanism of adduct formation was unclear. Here, the authors show that the covalent inhibitor-FAD adduct undergoes a Grob fragmentation and elucidate the structure-activity relationships that promote this transformation.

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.

Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.

Mutations of the histone H3K36-specific methyltransferase ASH1L have been linked to several human diseases. Here, the authors report the mechanism by which three C-terminal domains in ASH1L regulate its enzymatic activity and interact with chromatin.

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.

Climate warming has a wide range of effects on biodiversity. Here, Zhou et al. show that although variation in environmental temperature is a primary driver of soil microbial biodiversity, microbes show much lower rates of turnover across temperature gradients than other major taxa.

Brian Brown et al. report the results of the Zurquí All Diptera Biodiversity Inventory project, one of the largest efforts to date to directly assess species richness of a megadiverse order of insects. The authors identified 41,001 flies to 4332 species, including 73 of the world's 160 Diptera families.

Logic-based computation operates widely with discrete molecules of up to nanometric sizes, but artificial molecule-based meso-scale systems which intrinsically perform logic operations are rare. Here, the authors show that self-assembled systems consisting of cyclophaneoctacarboxylates and a cationic surfactant can perform such functions.

In a quasi-experimental, pre–post-implementation study involving 51,760 hospitalizations, an electronic health record-based risk prediction model informed clinicians of patients needing consultation on opioid use disorder and decreased readmissions to the hospital, without increasing referral rates and with promising cost-effectiveness results.

The herbicide propyzamide increases inflammation in the small and large intestine, and the AHR–NF-κB–C/EBPβ signalling axis—which operates in T cells and dendritic cells to promote intestinal inflammation—is targeted by propyzamide.

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.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

The mechanisms of pathological astrocyte responses during multiple sclerosis remain unclear. Kadowaki et al. found in MS mouse models that CLEC16A suppresses astrocyte pathogenic activities related to mitochondria by boosting mitophagy.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

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.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

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.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

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.

PLX4032 is a selective inhibitor of the B-RAF protein that has shown promising results in an early clinical trial in melanoma patients with an activating mutation in B-RAF. Now the structure and function of this inhibitor are described. Translational data from a phase I trial show that clinical efficacy requires a substantial degree of inhibition of the ERK pathway downstream of B-RAF. The data also show that BRAF-mutant melanomas are highly dependent on B-RAF activity.

Here, Qi et al. assembled ~3000 archaeal genomes from hot springs, capturing temporal dynamics and environmental diversity, and systematically explored functional niches and metabolic handoffs, shedding light on Archaea’s role in biogeochemical cycling.

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.

In a post hoc multiomics analysis of a trial comparing a plant-based, low-fat diet to an animal-based, ketogenic diet, the diets have differential effects on peripheral immune cell frequencies and immune-related gene expression.

Researchers identified 7 biological group of diffuse large B-cell lymphoma, one with poor prognosis. They developed a gene expression classifier to detect these groups, potentially improving prognosis and future treatments for the high-risk patients.