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Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

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.

Lactone monomers for recyclable polyesters are conventionally synthesized via endergonic, non-oxidative dehydrocyclization of fossil-derived diols in the vapor phase over precious-metal catalysts at elevated temperatures. Here, the authors demonstrate a low-temperature, solvent-free, oxidative route to lactones from bio-derivable liquid diols using earth-abundant calcium-copper mixed-metal oxide catalysts.

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.

T-cell acute lymphoblastic leukemia is a highly aggressive disease with varying recurrence rates. Here, the authors build a single cell transcriptomic atlas of childhood T-cell acute lymphoblastic leukaemia (T-ALL). They identified a distinctive cancer cell state that correlates with high risk, treatment refractory T-ALL.

Multiterminal Josephson junctions may provide a novel way to realize topologically non-trivial band structures in an n-dimensional phase space. Here, the authors experimentally demonstrate the proposed necessary conditions to measure these states.

Computational methods are becoming an increasingly important part of biological research. Using the Rosetta framework as an example, the authors demonstrate how community-driven development of computational methods can be done in a reproducible and reliable fashion.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Analysis of the immune microenvironment of diffuse B cell lymphomas using spatial transcriptomics, proteomics and genomics highlights discrete cellular niches with divergent patterns of cell–cell communication that contribute to the phenotypic heterogeneity of both tumor and immune cells.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Influenza genetic diversity is a key challenge in the design of a universal influenza vaccine that protects against different strains of influenza virus. Here, Malouli and colleagues demonstrate use of a cytomegalovirus-based T cell vaccine that induces immunity and can protect macaques from lethal avian influenza challenge with heterologous strains of influenza and suggest protection is linked to the generation of lung-resident influenza-specific CD4⁺ T cells.

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.

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.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

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, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other 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.

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.

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.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Genome sequencing of Zika virus samples from infected patients and Aedes aegypti mosquitoes in Florida shows that the virus was probably introduced into the United States on multiple occasions, and that the Caribbean is the most likely source.

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.

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.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

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.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

The link between stiffness heterogeneity and tumor cell heterogeneity remains poorly understood. Here, authors propose an AI-informed method that reveals correlations between stromal stiffness and breast cancer cells with a heterogeneous EMT phenotype.

Targeted protein degradation (TPD) can be employed to eliminate disease-causing proteins. Here, the authors present CYpHER, a TPD tool that uses molecules engineered for intracellular target release with drug recycling via transferrin receptor. CYpHER induces depletion of extracellular targets in vitro and in xenograft tumours.

Site-specific hyperphosphorylations of tau in the cerebrospinal fluid change with disease course, and correlate with pathology and cognitive decline in dominantly inherited Alzheimer’s disease.

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.

This study reports transposon sequencing analyses to identify genes required for Legionella pneumophila survival in amoeba hosts, showing that unique sets of genes are required for virulence in different amoebae. This enables the accumulation of virulence genes that collectively allow replication in macrophages and, in some cases, lead to redundancy in this host cell type.

Treatment of patients with advanced hepatocellular carcinoma with a personalized DNA vaccine in combination with anti-PD-1 therapy was safe and led to encouraging clinical efficacy, with immunological analyses confirming the induction of tumor antigen-specific T cell responses.