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A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Biochemical research on methane oxidation in anaerobic methanotrophic archaea is hampered by the lack of cultured isolates. Here, Müller et al. present atomic-resolution snapshots of the methane-oxidising enzymes purified from enrichment cultures, providing molecular insights into the process and revealing unusual post-translational modifications.

Experiments under upper-tropospheric conditions map the chemical formation of isoprene oxygenated organic molecules (important molecules for new particle formation) and reveal that relative radical ratios control their composition

This study reports clusters of ipsilateral eye preferring neurons in layer 4 of mouse visual cortex, extending into layer 2/3 and upper layer 5. This column-like pattern for ocular dominance expands our understanding of the functional organization in neocortex.

The Authors demonstrate imaging of separation and formation of chemical bonds during an elimination reaction by means of intense femtosecond X-rays pulses.

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.

Efficient production of dopamine direct from lignin is a highly desirable target but extremely challenging. Here, we report an innovative strategy for the sustainable production of dopamine hydrochloride from softwood lignin with a mass yield of 6.4 wt.%.

Cobalt–iron–lead oxide electrocatalysts show promise for the low-pH oxygen evolution reaction—an essential reaction in proton-exchange water electrolysis—but can suffer from corrosion. This study uncovers that the mechanism of cobalt site corrosion is decoupled from the oxygen evolution reaction, paving the way for more stable catalyst designs.

Class I and II benzoyl-coenzyme A reductases offer a mild biological alternative to the alkali metal- and ammonia-dependent Birch reduction, a classical synthetic method for achieving dihydro additions to arenes. Here, the authors characterize double-cubane [8Fe-9S] and active site aqua-[4Fe-4S] clusters of a class I benzoyl-CoA reductase and provide evidence for a radical mechanism.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

An efficient computational pipeline starting from validated peptide assemblies has been used to design two families of α-helical barrel proteins with functionalizable channels. This rationally seeded computational protein design approach delivers soluble, monomeric proteins that match the design targets accurately and with high success rates.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The hippocampus is thought to encode the content of stimuli, but how it does so is unknown. The authors show that when hippocampal spiking variability tracks the abstract building blocks of individual stimuli, memories are formed successfully.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

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.

The streptococcal enzymes IdeS and EndoS cleave IgG antibodies with exquisite substrate specificity, which has enabled their development as clinical and biotechnological tools. Here, the authors present crystal structures of both enzymes in complex with their IgG1 Fc substrate.

Ossenkoppele, Coomans and colleagues analyzed the tau PET data of 12,048 individuals from 42 cohorts worldwide. They found that age, amyloid-β status, presence of an APOE ε4 allele and female sex are key contributors to tau PET positivity, which should aid clinical decision-making and trial designs.

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.

MRI data from more than 100 studies have been aggregated to yield new insights about brain development and ageing, and create an interactive open resource for comparison of brain structures throughout the human lifespan, including those associated with neurological and psychiatric disorders.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Ionizing radiation from cosmic rays has been identified as a source of correlated errors in superconducting qubits, but a direct demonstration of this link has been lacking. Here the authors measure the coincidence between correlated errors and incident cosmic rays in a chip with 10 transmon qubits.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

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.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

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.

Biochemical, structural and genetic analysis of the shelterin complex reveal that by recruiting RAP1 to DNA, TRF2 directly inhibits DNA-dependent protein kinase to regulate classical non-homologous end joining at telomeres.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Through the development of novel PKC biosensors, the authors describe how PKCα, but not other classical isozymes, facilitates plasticity in dendritic regions through the integration of recent synaptic plasticity with current, local synaptic input.

Transcriptional adaptation upregulates UTRN in Duchenne muscular dystrophy (DMD) patients, as supported by several lines of evidence, including the use of splice-switching antisense oligonucleotides to induce the skipping of out-of-frame exons of the DMD gene.

Reduced flexibility is a hallmark of cognitive ageing. Here, the authors examine EEG, fMRI and pupillometry signatures to show that older adults adapt less to variable uncertainty and identify neural mechanisms that support uncertainty adjustment in aging populations.