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An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

In vitro library screening is a powerful approach to identify functional biopolymers, but only covers a fraction of possible sequences. Here, the authors use experimental in vitro selection results to train a conditional variational autoencoder machine learning model that generates biopolymers with no apparent sequence similarity to experimentally derived examples, but that nevertheless bind the target molecule with similar potent binding affinity.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

EvoScan combines EvolvR mutagenesis and phage selection to explore the protein sequence space in different dimensions, identifying anchor points with critical mutations. Next, EvoAI, a deep learning-based method, uses these anchor points to accurately reconstruct the protein sequence space and design new proteins.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Knowledge of the electronic structure of group-IV monochalcogenides is essential for their application in high-performance thermoelectric energy harvesting. Here, using photoemission spectroscopy, the authors reveal the impact of doping, and the anisotropic nature of the band structure of SnSe.

Vortices in light fields are of growing importance in the XUV and X-ray ranges. Here the authors show by simulations that high harmonics and attosecond pulses, generated while irradiating a deformed thin foil with circularly-polarized Gaussian laser pulses, carry a well-defined orbital angular momentum.

Comprehensively understanding the ultrafast dynamics of the insulator-to-metal transition in vanadium dioxide is a long-standing challenge. Here, the authors measure the electronic and structural phase transitions in the first hundred femtoseconds.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Cuprate superconductors are created by adding electrons or holes to a ‘parent’ compound. They have dissimilar phase diagrams and the asymmetry is further highlighted by unexpected collective modes measured using resonant inelastic X-ray scattering.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

It is important yet challenging to elucidate the mechanism of water dissociation in bipolar membrane electrolysers. Here the authors show how water dissociation is accelerated by electric-field-focusing and catalytic effects and uncover design principles to optimize the performance.

Here the authors report a computational approach which integrates deep learning and structural modelling to design target-specific peptides. They apply this to β-catenin and NF-κB essential modulator, resulting in improved binding, highlighting the efficacy of this strategy.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Observation of the entire dispersion relation for spin waves remains a challenge which prevents the full understanding of many intriguing magnetic properties. Here, the authors develop a table-top all-optical approach to map out the dispersion curve of pure-magnetostatic waves in magnetic films.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Ten years after the discovery of the Higgs boson, the ATLAS  experiment at CERN probes its kinematic properties with a significantly larger dataset from 2015–2018 and provides further insights on its interaction with other known particles.

Yin et al. harmonized 1,091 fMRI scans across five imaging cohorts to map developmental trajectories of brain functional connectivity in early childhood, revealing early brain development and its links to cognitive abilities.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

During a photoinduced phase transition, electronic rearrangements are usually faster than lattice ones. Time-resolved measurements now show that the insulator-to-metal transition in a thin-film Mott insulator is preceded by lattice reconfiguration.

The orphan enzyme phosphotriesterase-related (PTER) is identified as a mammalian N-acetyltaurine hydrolase that has roles in regulating body weight and energy balance.

Controlling Li nucleation and growth is crucial to avoid dendrite formation. Here, Li₂S(111)@Cu is used as Li metal electrode substrate, where a substrate-dependent Li nucleation process and a facet-dependent growth mode are identified, enabling dense Li deposition and improved battery performance.

The authors study interface superconductivity in over-doped La_2-xSr_xCuO₄/La₂CuO₄ heterostructures. As x increases, the superconductivity is killed at x = 0.8 but fully recovers at x = 1.0, a “re-entrant” superconductivity.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

A multi-cohort genome-wide association study of tau PET, a brain imaging-based marker of Alzheimer’s disease, identifies a CYP1B1-RMDN2 locus as associated with higher tau and faster cognitive decline. These results suggest a new genetic contribution to cerebral tau and target for Alzheimer’s disease research.

Snyder and colleagues show global loss of promoter–enhancer connectivity during early colorectal carcinogenesis and the dependency of gene dysregulation during this process on the baseline of promoter–enhancer interaction in normal colonic epithelium.

Changes in intracellular GTP levels are not considered as a regulatory event in RAC1 activation in live cells since total GTP levels are substantially higher than the RAC1 GTP dissociation constant determined in vitro. Here, the authors demonstrate that the availability of free GTP in live cells controls the activity of RAC1 and cell invasion.

The oxygenation of deeper continental shelf waters during the Mesoproterozoic coincided with the appearance of multicellular eukaryotes, according to geochemical and sedimentological analyses of the Yanliao Basin, China.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

In situ Hi-C and other genome-wide and imaging analyses in different mouse embryonic cell types reveal that the noncanonical SMC protein Smchd1 regulates long-range chromatin interactions and the developmental silencing of Hox genes.