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Two sequence-verified, clonal, publicly available collections of human open reading frames are reported. One collection is in a lentiviral vector for expression in mammalian cells; the other is in the Gateway vector system.

Levels of circulating thyrotropin and free thyroxine reflect thyroid function, however, their genetic underpinnings remain poorly understood. Taylor et al. take advantage of whole-genome sequence data from cohorts within the UK10K project to identify novel variants associated with these traits.

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

Population-based genome sequencing provides an increasingly rich resource for the identification of low-frequency, large effect variants associated with clinically important phenotypes. Timpson et al. use UK10K data to identify a variant of the APOC3gene strongly associated with plasma triglyceride levels.

As the sample size in cancer genome studies increases, the list of genes identified as significantly mutated is likely to include more false positives; here, this problem is identified as stemming largely from mutation heterogeneity, and a new analytical methodology designed to overcome this problem is described.

Size and shape of the brain are, among others, influenced by the dimensions of the skull. Here, the authors report genome-wide association studies for head circumference and intracranial volume in children and adults and the identification of nine common or low-frequency variants associated with these traits.

Vicinity of small bodies might be dangerous to the spacecrafts and to their instrumentation. Here the authors show the operational environment of asteroid Bennu, validate its photometric phase function and demonstrate the accelerating rotational rate due to YORP effect using the data acquired during the approach phase of OSIRIS-REx mission.

Bennu’s surface has experienced continuous changes, mostly induced by its accelerating spin rate, which could have resulted in a collapse of its interior in the past. This scenario is also supported by the heterogeneity of Bennu’s internal mass distribution.

The authors show that the neuron-specific LSD1 variant (LSD1n) promotes transcription initiation and elongation in response to neuronal activity. LSD1n is essential for spatial learning and long-term memory formation. LSD1n exhibits novel substrate specificity for histone H4 K20 methylation.

Genes encoding subunits of the SWI/SNF chromatin-remodeling complex constitute, collectively, one of the most frequently mutated targets in cancer. Although mutations in SWI/SNF genes are uncommon in prostate cancer, a new study shows that SChLAP1, a long noncoding RNA frequently expressed in aggressive prostate tumors, drives cancer by directly disrupting SNF5, a core subunit of the SWI/SNF complex.

Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Treatment with BRAF and/or MEK inhibitors followed by addition of anti-PD-L1 in BRAF-mutant melanoma patients is safe and shows promising anti-tumor activity.

Signatures of phyllosilicate-like hydrated minerals are widespread on Bennu’s surface, indicating significant aqueous alteration. The lack of spatial variations in the spectra down to the scale of ~100 m indicates both a relatively uniform particle size distribution and a lack of compositional segregation, possibly due to surficial redistribution processes.

Human pluripotent stem cells have been shown to be important models for interrogating the molecular basis for heart disease. This review highlights the contributions of these models to our understanding of inherited arrhythmia syndromes, with a focus on integrating mechanistic and genome-wide association study data.

When considering how ecosystems will react to climate change the importance of dead matter has been largely overlooked. Here we discuss why dead material is integral to ecosystem form and function, and why its persistence or degradation must be explicitly included in models considering ecosystem futures in a rapidly changing world.

Global climate models are challenging to integrate in energy system models because their output data resolution is too coarse. Buster et al. generate high-resolution meteorological data with climate change impacts from global climate model datasets using generative machine learning.

Recent data from early clinical trials in melanoma patients carrying mutations in the B-RAF gene have shown promising results with the B-RAF kinase inhibitor PLX4032; however, many patients eventually develop resistance to this treatment. Two papers now uncover possible mechanisms of resistance to PLX4032. One paper shows that upregulation of MAP3K8 (which encodes COT) can confer resistance of melanoma cells to B-RAF inhibitors, whereas another paper found that melanomas can acquire resistance due to mutations of N-RAS or increased expression of PDGFRβ. Each of these resistance mechanisms seems to apply to at least some patients on recent PLX4032 trial, whereas, surprisingly, so far no secondary B-RAF mutations have been observed.

Squeezed states of light have been experimentally demonstrated to improve the performance of the Laser Interferometer Gravitational-wave Observatory (LIGO) in astrophysically relevant frequency regions. This enhanced performance may help to reach the sensitivity required for detecting gravitational waves.

BET inhibitors that target bromodomain chromatin readers such as BRD4 are being explored as potential therapeutics in cancer; here triple-negative breast cancer cell lines are shown to respond to BET inhibitors and resistance seems to be associated with transcriptional changes rather than drug efflux and mutations, opening potential avenues to improve clinical responses to BET inhibitors.

Whole-genome sequencing of 85 families with two affected siblings reveals considerable genetic heterogeneity in autism spectrum disorder.

Yuen et al. developed a cloud-based database with 5,205 whole genomes from families with autism spectrum disorder (ASD). They identified 18 new candidate ASD-risk genes and approximately 100 risk genes and copy-number loci, which account for 11% of the cases. They also found that individuals bearing mutations in ASD-risk genes had lower adaptive ability.

In an inter-laboratory study, the authors compare the accuracy and performance of three optical density calibration protocols (colloidal silica, serial dilution of silica microspheres, and colony-forming unit (CFU) assay). They demonstrate that serial dilution of silica microspheres is the best of these tested protocols, allowing precise and robust calibration that is easily assessed for quality control and can also evaluate the effective linear range of an instrument.

Osteosarcoma is the most common primary malignant tumour of the bone. This Primer by Gorlick and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of this disorder as well as the quality of life of patients and open research questions.

Trevor Cannon and colleagues evaluate the impact of a carbon-free, ammonia-powered propulsion system on contrail formation during flight. The report suggests that there are benefits compared to the use of conventional jet fuel from reduced soot formation. However, the increased critical temperatures caused by burning ammonia result could lead to increased volumes of more enduring contrails at lower altitudes.

Observations of asteroid (101955) Bennu with NASA’s OSIRIS-REx spacecraft reveal an unexpected surficial diversity that poses a challenge to the success of the sample-return mission.