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Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Spatially resolved gene expression during barley development was done by integrating an scRNA-seq dataset from cells with unknown position with spatial transcriptomics. This dataset is publicly available through the online web-based BARVISTA application.

How the nervous system controls social behaviours of bees is poorly understood. This study finds that social feeding of male honeybees is hardwired into the nervous system by the fruitless (fru) gene, and that expression of this transcription factor is restricted to the nervous system of males.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

Using brain organoids models, Prigione and colleagues uncovered the impact of Huntington’s disease on human brain developmental and identified early dysregulation of CHCHD2, which disrupted mitochondria and might serve as a therapeutic target.

Sexual dimorphism results in widely diverse animal forms, but sexual determination is generally attributed to a single gene in animal models. Here they find that the glu gene regulates sexual dimorphism of honeybee eyes, demonstrating diversification of genetic programs for dimorphism.

Intermediate-coverage long-read sequencing in 1,019 diverse humans from the 1000 Genomes Project, representing 26 populations, enables the generation of comprehensive population-scale structural variant catalogues comprising common and rare alleles.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

Our ability to identify associations between behaviour and brain imaging is important for uncovering markers of cognition and disease. Here, the authors illustrate the importance of the reliability of behavioural measurements to accurately investigate brain-behaviour associations using machine learning.

Viruses are promising anti-tumour therapeutics due to induction of an immune response and/or oncolytic activity. Here, Kalkavanet al. show that LCMV replicates in tumour cells, without inducing cell lysis, and that its anti-tumour activity is largely mediated by recruitment of interferon-producing monocytes.

Grasses have evolved a wide variety of inflorescence architectures. Here Vardanega et. al show how the barley CLV1 receptor and FCP1 peptide signal interact to control meristem shape, organ formation and determinacy thus shaping barley spike morphology.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Chronic disturbances in autonomic regulation are increasingly recognized as contributors to metabolic diseases such as obesity and type 2 diabetes mellitus. In this Review, Wangler and colleagues discuss bidirectional communication between the autonomic nervous system and peripheral tissues in the coordination of glucose and lipid metabolism as well as emerging therapies targeting autonomic pathways that could improve metabolic health.

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.

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.

‘Gasdermin-mediated pyroptosis can induce anti-tumor immune responses. Here the authors report a toolbox of gasdermin D variants for induction of pyroptosis, showing that, when combined with intratumoral expression of cytokines (IL-1β, IL-12, or IL-18), anti-tumor immune responses in preclinical models are enhanced.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

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.

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.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

Central insulin effects on brain networks and food cue reactivity in the hippocampus and striatum vary dynamically across the menstrual cycle in premenopausal women, with estradiol and progesterone predicting these changes.

Serine recombinases are proposed to catalyse DNA site-specific recombination by a unique mechanism called subunit rotation. Here, the authors use single molecule FRET to provide direct structural and kinetic evidence for subunit rotation by two distantly related recombinases, Tn3 resolvase and Sin.

Goede et al. combined multiple modalities to define a common tremor network across disorders. This finding may help optimize deep brain stimulation and guide future noninvasive therapies.

Paediatric high-grade gliomas with MYCN amplification (HGG-MYCN) are rare and highly aggressive. Here, the authors generate a mouse model for HGG-MYCN that can recapitulate the histological and molecular profiles of the human tumours, and perform high-throughput drug screening to identify potential treatment options.

Constructing genome graphs directly from genome assemblies overcomes single-reference bias.

Phylogenetic analysis shows that site-exclusion methods produce erratic phylogenetic estimates of mitochondrial origin and support an origin of mitochondria within Alphaproteobacteria.