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Ataxia Telangiectasia and Rad3-related (ATR) is a key regulator of replication stress response; yet, mutations within the ATR gene cause human ATR-Seckel Syndrome associated with microcephaly and intellectual disability. Here, the authors show neuron-specific ATR deletion increases intrinsic neuronal and epileptiform activity, revealing a function of ATR beyond its role in DNA damage response.

Spectroscopic studies and theoretical calculations of the electrocatalytic oxygen evolution reaction establish that reaction rates depend on the amount of charge stored in the electrocatalyst, and not on the applied potential.

The oxygen evolution reaction proceeds over a surface that undergoes (frustrated) phase transitions to accommodate bias-dependent excess charge. Now it has been shown that this excess charge is intimately linked to the interfacial solvation of ions and the pre-organization of the transition state, providing insight into intrinsic catalyst activities.

The nature of the active species over Cu/ZnO catalysts for methanol synthesis remains elusive. Here, the authors shed light on the evolution of the nanoparticle/support interface and correlate its structural and chemical transformations with changes in the catalytic performance.

Understanding of catalyst structure and reactivity is important for the development of water splitting catalysts. Here, the authors report reversible structural transformation of the near-surface of crystalline Co₃O₄ electrocatalysts to an amorphous CoO_x(OH)_yduring oxygen evolution.

Cobalt-based oxidic anodes with added iron are good electrocatalysts for alkaline oxygen evolution reaction, but the role of iron is still unclear. Here the authors investigate oxygen evolution reaction activity of three well-defined epitaxial thin-film electrodes to address this issue.

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.

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.

Knowledge of the energy transfer pathways in transition metal dichalcogenides is essential to design efficient optoelectronic devices. Here, the authors use megaelectronvolt ultrafast electron diffraction to unveil the sub-picosecond lattice dynamics in MoSe₂ following photoexcitation of charge carriers

Electrochemical reduction of CO₂ can yield many different products; a better understanding of the key mechanisms at play is needed to guide the design of selective catalysts. Here the authors use in situ surface-enhanced Raman spectroscopy and simulations to elucidate reaction schemes for CO₂ reduction to ethylene and ethanol.

The near-surface structure of oxide electrocatalysts during the oxygen evolution reaction is key to performance but remains elusive. Here the authors use operando X-ray absorption spectroscopy to track the size-dependent catalytic activity of CoO_x(OH)_y nanoparticles down to 1 nm and their structural changes under reaction conditions.

Copper-nitrogen co-doped carbon catalysts reversibly transform into metal clusters, when employed for the electrocatalytic CO2 reduction. Here, by applying potential pulses, the authors show the size of the formed metal clusters can be finely tuned, allowing on-the-fly steering of the distribution of reaction products.

The relationship between product selectivity and catalyst structure under dynamic reaction conditions has proved difficult to interpret in electrocatalytic CO₂ reduction. Here, the authors combine operando X-ray techniques with high time resolution to investigate control over product selectivity using potential pulses.

CtBP is a transcriptional master co-repressor with oncogenic activity. Here, the authors use structural and biophysical methods to show that CtBP interacts with RAI2 through SLiMs that induce CtBP polymerization and inactivation.

Controlling the selectivity of the electroreduction of CO₂ to value-added products is challenging. Here, authors use sub-second operando Raman spectroscopy to analyze Cu catalyst surfaces and discover the pivotal role of co-adsorbed OH and CO in enhancing ethanol selectivity.

Studies based on correlated operando characterization techniques reveal the coexistence of copper metal, oxide and hydroxide phases during the electrochemical reduction of nitrates to ammonia, providing insights into electrocatalyst evolution during reaction and related catalytic performance.

Copper is an important catalyst for CO₂ electroreduction as it enables the formation of multi-carbon products. Now, using various in situ techniques, the authors show that low-coordinated Cu surface species form spontaneously near the onset of CO₂ electrocatalytic reduction.

NiFe and CoFe layered double hydroxides are among the most active electrocatalysts for the alkaline oxygen evolution reaction. Here, by combining operando experiments and rigorous DFT calculations, the authors unravel their active phase, the reaction center and the catalytic mechanism.

Knowledge of the active sites in catalysts—including the sites that form under working conditions—is vital for future design and development. Here, the authors track the atomic-scale changes in a series of well-defined cobalt-based oxide electrocatalysts, showing that the structurally distinct catalysts develop a similar structural motif as they transform into the catalytically active state.

Burkitt lymphoma (BL) is the most common pediatric B-cell lymphoma. Here, within the International Cancer Genome Consortium, the authors performed whole genome and transcriptome sequencing of 39 sporadic BL, describing the landscape of mutations, structural variants, and mutational processes that underpin this disease how alterations on different cellular levels cooperate in deregulating key pathways and complexes.

Inhibition of YBX1, a downstream target of the Janus kinase JAK2, sensitizes myeloproliferative neoplasm cells to JAK and could provide a means to eradicate such cells in human haematopoietic cancers.

The precise understanding of the active phase under reaction conditions at the molecular level is crucial for the design of improved catalysts. Now, Strasser, Jones and colleagues correlate the high activity of IrNi@IrO_x core–shell nanoparticles with the amount of lattice vacancies produced by the nickel leaching process that takes place before and during water oxidation, and elucidate the underlying structural-electronic effects.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

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.