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Clouds on Titan result from the condensation of methane and ethane and, at present, cloud activity mainly occurs in the southern hemisphere; general circulation models predict that this distribution should change with the seasons on a 15-year timescale. Now, global spatial cloud coverage on Titan is reported to be in general agreement with the models.

Most genetic association studies have been done on single nucleotide polymorphisms and small indels, while other types of variants have been less studied. Here, the authors use whole genome sequencing in a diverse population to identify and provide experimental evidence for associations between structural variants and blood-cell traits.

Two stars born at the same time, from the same natal material, and with the same mass are 'identical twins', and as such might be expected to possess identical physical attributes. But this paper reports that a pair of twin stars have surface temperatures that differ by ∼300 K and luminosities that differ by ∼50 per cent. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling.

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.

Grieger, Takele, Vesco, et al. perform a systematic review and meta-analysis of gestational weight gain interventions. Findings indicate lifestyle interventions that reduce excessive gestational weight gain provide greater benefits for women with a normal BMI and higher HDL cholesterol levels at the initiation of interventions.

High-throughput peptide synthesis and mass spectrometry are used to generate a near-complete reference map of the Saccharomyces cerevisiae proteome; two versions of the map (supporting discovery- and hypothesis-driven proteomics) are then applied to a protein-based quantitative trait locus analysis.

Ewing sarcoma (EWS) is a rare pediatric bone cancer typically involving the EWSR1-FLI1 fusion. Here the authors perform a genome-wide association study and report three new EWS risk loci that reside near GGAA repeat sequences, and identify candidate genes (RREB1 and KIZ) from eQTL analysis.

Matthew Brown, Peter Donnelly and colleagues report results of a genome-wide association meta-analysis and follow-up study of ankylosing spondylitis. They identify three new risk variants and report a genetic interaction between ERAP1 and HLA-B27, implicating aberrant peptide handling in the pathophysiology of this disease.

Integrating inventory data with machine learning models reveals the global composition of tree types—needle-leaved evergreen individuals dominate, followed by broadleaved evergreen and deciduous trees—and climate change risks.

In this Review the authors explore the emerging role of HER2 in urothelial carcinoma, highlighting its biological and clinical significance, the challenges of using HER2 as a biomarker, and the variability and complexity of HER2 assessment. Evidence supporting HER2-targeted therapies and future directions for research and clinical applications are also discussed.

Housheng Hansen He and colleagues perform an integrated analysis and identify 45 candidate long noncoding RNAs (lncRNAs) associated with prostate cancer risk. They further show that a prostate cancer risk allele in the 8q24 region results in upregulation of the lncRNA PCAT1, which promotes prostate cancer cell proliferation and tumor growth.

Frequencies of rare variants fluctuate over populations, hampering gene discovery. Here the authors use a population-specific reference panel, the Genome of the Netherlands, to discover four novel loci involved in lipid metabolism, including an exonic variant in ABCA6.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

C9orf72 expansion mutations are the most common genetic cause of ALS and FTD, which have limited therapies. The authors generate stereopure oligonucleotides that selectively deplete expansion-containing transcripts and protect against expansion-associated pathologies in preclinical models.

Understanding the molecular basis of leukaemia predisposition is essential for intervention. The authors here investigate germline genetic leukaemia predisposition by studying Shwachman-Diamond syndrome and report compensatory inactivating mutations in EIF6 and transforming biallelic TP53 alterations.

Paul de Bakker, Cisca Wijmenga and colleagues report on The Genome of the Netherlands Project, including whole-genome sequencing of 769 individuals of Dutch ancestry from 250 parent-offspring families and construction of a phased haplotype map. Their intermediate-coverage population sequencing data set provides a complementary resource to other publicly available data sets, including the 1000 Genomes Project.

The crystal structure of the CCR9 chemokine receptor in complex with vercirnon at 2.8 Å resolution.

Crystal structures of protease-activated receptor 2 (PAR2) in complex with two different antagonist ligands and with a blocking antibody reveal binding sites that are distinct from those found on PAR1, offering new leads for structure-based drug design.

New low-affinity anti-CD19 CAR T cells exhibit peripheral expansion and persistence without inducing severe cytokine-response syndrome in pediatric patients with relapsed or refractory B cell acute lymphoblastic leukemia.

The crystal structure of the complement receptor C5aR1 bound to a small-molecule antagonist provides insights into this receptor class and how they could be better targeted therapeutically.

Sequencing of the genome of the butterfly Heliconius melpomene shows that closely related Heliconius species exchange protective colour-pattern genes promiscuously.

Tomi Pastinen and colleagues report a genome-wide analysis of allelic expression variation in lymphoblastoid cell lines from HapMap individuals.

The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response.

The APOE4 allele is the leading risk factor for late-onset Alzheimer’s disease, but how it might contribute to the disease is not clear. Here the authors show that a mouse expressing the human APOE4 allele displays hyperactivity in the entorhinal cortex due to a decreased inhibitory tone, which may in part explain accelerated Alzheimer’s pathology in APOE4 carriers.

Measurements of sediments eroded by the Mackenzie River reveal the widespread export of permafrost-derived biospheric carbon that is several thousand years old, and demonstrate its burial in the Arctic Ocean, suggesting that high-latitude rivers can act as important carbon dioxide sinks.

Jacobsen, Sherr et al. evaluate the utility of novel technologies in the treatment of type 1 diabetes. Their systematic review finds technologies such as continuous glucose monitoring, insulin pumps, and decision support tools improve important measures (e.g., HbA1c, time in range, quality of life) allowing precision-directed uptake of technology.

Structural variants (SVs) are prevalent in genomes of the general population. Here, Guryev and The Genome of the Netherlands Consortium describe the reference panel of haplotype-resolved SVs from 769 individuals from 250 Dutch families and show its utility for studying heritable traits.

The genome of the wild grass Brachypodium distachyon (Brachypodium), a member of the Pooideae subfamily, is sequenced. The Pooideae are one of three subfamilies of grasses that provide the bulk of human nutrition and may become major sources of renewable energy. Availability of the genome sequence should help establish Brachypodium as a model for developing new energy and food crops.

Wei Zheng and colleagues report genome-wide analyses in east Asians and identify three new loci associated with colorectal cancer risk.

Genetic variants in the germ line modulate DNA methylation in tumors and contribute to the aggressiveness of prostate cancer.

In this Roadmap arising from an NHLBI workshop, Chew and colleagues explore the use of retinal imaging biomarkers for the prediction, diagnosis and monitoring of systemic cardiovascular diseases. The authors identify knowledge gaps and research opportunities to translate retinal imaging biomarkers into clinical practice.

Richard Lifton, Véronique Frémeaux-Bacchi and colleagues report that recessive mutations in DGKE cause atypical hemolytic-uremic syndrome with an early age of onset progressing to chronic kidney disease. The authors propose that loss of DGKE results in a prothrombotic state that underlies disease pathogenesis.

The measurement of the rotational periods of 30 cool stars in the 2.5-billion-year-old cluster NGC 6819 allows the calibration of gyrochronology — the determination of a star’s age on the basis of its rotation period — over a much broader age range than hitherto, meaning that it might be possible to determine the ages of many cool stars in the Galactic field with a precision of roughly 10 per cent.