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Iron derived from debris eroded by the West Antarctic Ice Sheet rather than from dust deposition drove variations in carbon export in the South Pacific Antarctic region over the past 500,000 years, according to geochemical proxies from a sediment core.

The authors present a deep learning approach to uncover complex genetic effects on circulating protein levels. They reveal new interactions and dominance patterns using UK Biobank proteomics data.

The temporal regulation of intracellular insulin signaling is not well studied. Here the authors conducted a time-resolved analysis of the global insulin-regulated phosphoproteome in human muscle cells, revealing synchronized signaling pathways for propagating information to insulin effector sites.

This mass spectrometry-based proteomic study profiles the plasma proteome in 2,147 children and adolescents and reveals its association with age, sex, puberty, body mass index and genetics.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

Analysis of human genotypes and 16S microbiome data of 18,473 individuals from 25 cohorts through a genome-wide association study, a phenome-wide association study and Mendelian randomization identifies host genetic and microbial trait associations.

G protein-coupled receptors (GPCRs) are critical drug targets that undergo conformational changes upon ligand binding. Here, authors developed photochemical switches for the adenosine A2A receptor and followed ligand dissociation using time-resolved crystallography.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.

RNA polyadenosine tails are important for the export, translation and stability of mRNAs and play a role in non-coding RNA biogenesis. Here the authors measure yeast poly(A) tail lengths by direct RNA sequencing, revealing its dynamics in yeast exonuclease, deadenylase and poly(A) polymerase mutants.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Sequencing the microbial species present in complex metagenomic samples is made easier with a method that groups genes by co-abundance.

Increased potential for branched-chain amino acid and lipopolysaccharide biosynthesis in the gut microbiome of insulin-resistant individuals suggests that changes in the serum metabolome induced by dysbiosis, and driven by only a handful of species, contribute to the development of diabetes.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.

Analysis of the gut microbial gene composition in obese and non-obese individuals shows marked differences in bacterial richness between the two groups, with individuals with low richness exhibiting increased adiposity, insulin resistance, dyslipidaemia and inflammation; only a few bacterial marker species are needed to distinguish between individuals with high and low bacterial richness, providing potential for future diagnostic tools.

How the carbon stocks of the Arctic–Boreal Zone change with warming is not well understood. Here the authors show that wildfires and large regional differences in net carbon fluxes offset the overall increasing CO₂ uptake.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

Heart failure with preserved ejection fraction (HFpEF), which can be driven by obesity and hypertension, has a high prevalence but limited treatment options. Here, the authors show that nitro-oleic acid restores mitochondrial function and improves heart failure symptoms in a mouse model of HFpEF.

Interogation of mass-spectrometry-based proteomics of liver and plasma from a cohort of patients with alcohol-related liver disease identifies noninvasive biomarkers associated with early stages of disease progression, including significant fibrosis, inflammation and steatosis.

Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

The design of efficient and selective catalysts is a formidable challenge in chemical science. Here the authors design a data-driven workflow to achieve the digitalized knowledge transfer between the synthetically relevant transformations, which was demonstrated in the prediction of chiral carboxylic acid co-catalyst for the cobalt-catalyzed asymmetric C–H alkylation of indoles.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

The levels of 1,251 metabolites are measured in 475 phenotyped individuals, and machine-learning algorithms reveal that diet and the microbiome are the determinants with the strongest predictive power for the levels of these metabolites.

Gene expression profiles can classify breast cancer into five clinically relevant subtypes. Here, the authors perform an in-depth quantitative profiling of the proteome of 45 breast tumors, and show they can recapitulate the transcriptome-based classifications and identify many potentially antigenic tumour-specific peptides.

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.

TMAO is known to be atherothrombotic. Here the authors show that i) kidney function is the main determinant of serum TMAO, ii) TMAO increases kidney scarring with TGF-β1 signalling and iii) anti-diabetic drugs with reno-protective properties such as GLP1R agonists reduce plasma TMAO.

Genome-wide association analyses of two oral glucose tolerance test-derived measures of postprandial insulin resistance discover ten new loci. Functional characterization identifies nine candidate genes implicated in the regulation of GLUT4.

Clinical multi-omics data are integrated and analyzed using a generative deep-learning model.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

Humans integrate sensory cues across multiple modalities to guide behaviour. Here, the authors report long-range phase synchronization between auditory and olfactory cortices prior to odor arrival, in a task where sound cues predict odors.

This study examines Arabica coffee production responses to key seasonal climate drivers, namely, temperature, precipitation, soil moisture and vapour pressure deficit, in 13 of the world’s most important producing countries. Through threshold regression and generalized additive models, threshold responses are identified that could translate into rapid coffee yield declines under climate change.

There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. In this study, authors demonstrate that axonal retrograde transport of BDNF/TrkB in neuronal amphisomes is involved in plasticity-relevant local signaling at presynaptic boutons and that SIPA1L2, a member of the SIPA1L family of neuronal RapGAPs, associates via LC3b to TrkB-containing amphisomes to regulate its motility and signaling at the axon terminals

Brain functions require a constant supply of glucose. However, the brain energy stores are unclear. Here, the authors show that oligodendroglial fatty acid metabolism can be an energy reserve for white matter axons, supporting their function.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Yun Chen, Albin Sandelin, Torben Heick Jensen and colleagues describe general rules governing the expression of reverse-oriented promoter upstream transcripts (PROMPTs) based on the orientation and proximity of promoter pairs. They characterize how the distance between promoters affects the expression of PROMPTs and the usage of alternate mRNA transcription start sites.

Oxaliplatin resistance in colorectal cancers is a major clinical problem, and predictive markers are urgently needed. Here, the authors show that miR-625-3pexpression reduces the sensitivity of colorectal cancer cells to oxaliplatin by targeting the kinase MAP2K6, an activator of the MAPK14 pathway.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

A vaccine to generate durable HIV broadly neutralizing antibodies (bnAb) from engineered B cells holds promise as an HIV functional cure. Here, the authors show that CRISPR/Cas-modified B cells expressing bnAbs as functional antigen receptors can be immunized to generate long-lived, germinal centre matured bnAb memory and plasma cells in mice.

The nuclear cap–binding complex (CBC) stimulates RNA maturation, but the mechanistic basis is not well understood. In vitro reconstitution experiments combined with functional analyses have revealed a new CBC complex containing ARS2, a major effector of CBC. ARS2 links the cap to 3'-end maturation for several RNA families, thus favoring the production of short RNAs.

Deep metagenomic sequencing and characterization of the human gut microbiome from healthy and obese individuals, as well as those suffering from inflammatory bowel disease, provide the first insights into this gene set and how much of it is shared among individuals. The minimal gut metagenome as well as the minimal gut bacterial genome is also described.

A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs.