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Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

Here, the authors show that IRX3 is a transcriptional master regulator of multiple histone- and chromatin-remodeling enzymes and the SUMOylation pathway in adipocyte precursor cells. IRX3 ablation results in a SUMOylation-dependent switch from adipogenic to osteogenic identity.

Joint profiling of chromatin and splicing in the brain uncovers shared and distinct patterns.

Pan-cistrome of the maize leaf under well-watered and drought conditions profiled by haplotype-specific MOA-seq highlights the relevance of transcription factor binding QTLs for understanding phenotypic diversity in maize.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Tailored non-aqueous electrolyte solutions are formulated using data obtained from extensive analytical measurements and analyses. These optimized electrolytes improve the cycling performance of single-layer stack lithium metal pouch cells, particularly in lean electrolyte conditions.

Patients with metastatic cancers of unknown primary (CUP) are currently unable to gain access to drugs through standard of care or clinical trials. Here, the authors perform whole-genome and transcriptome sequencing (WGTS) on 72 patients with CUP and demonstrate the feasibility of using WGTS to determine the specific cancer types of CUP, thereby clinically benefiting patients with CUP.

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.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

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.

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.

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.

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.

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.

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.

Aldolases have been a mainstay in synthesis, but their scope has been limited to activated electrophiles. Now carbon–carbon bond formation with ketone electrophiles is enabled by transaldolases, which form a strong nucleophile that is resistant to protonation. This chemistry enables convergent synthesis of non-canonical amino acids bearing tertiary alcohol side chains.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

The authors report TEQUILA-seq, a versatile, easy-to-implement, and low-cost method for targeted long-read RNA sequencing. TEQUILA-seq uncovers transcript isoforms and RNA mechanisms associated with human health and disease.

Cell-traversal protein for ookinetes and sporozoites (CelTOS) is a malaria vaccine candidate. Here, the authors characterize mouse monoclonal antibodies recognizing different CelTOS epitopes, and demonstrate protection from transgenic parasites containing P. falciparum or P. vivax as well as multistage activity.

Increases in high-impact marine heatwaves over the past few decades are found to be due to recent acceleration in long-term ocean surface warming, stressing the need of careful attribution of climate change impact on extreme events.

Inhibiting POLR2A expression upon siRNA delivery represents a promising therapeutic strategy for triple negative breast cancers characterized by p53 inactivation.

Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.

The establishment of glucose-regulated insulin secretion from pancreatic β-cells requires multiple transcription factors but is incompletely understood. Here, the authors show that Mediator complex subunit MED15 is vital for this process of β-cell maturation, highlighting its role in coordinating transcriptional control of insulin production and secretion.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

In studies using mouse models of psoriasis, a spectrum of innate lymphoid cell types is reconfigured and converges via multiple trajectories on a type 3-like state, demonstrating the range and flexibility of innate lymphoid cell responses in the skin.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Fanzor is shown to be an RNA-guided DNA endonuclease, demonstrating that such endonucleases are found in all domains of life and indicating a potential new tool for genome engineering applications.

Conservation biologists have made calls for including human dimensions in wildlife conservation efforts. This quantitative synthesis of case studies from a global IUCN reintroduction program suggests that inclusion of local stakeholders in wildlife restoration programs boosts success rate.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Results are presented that indicate that alterations to gene regulatory three-dimensional architecture are a critical mechanism that enables structural variant-based oncogene activation in cancer genomes and sheds light on the essential elements for such gene activation events.