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Researchers have gathered on the island of Heligoland to celebrate the centenary of Werner Heisenberg's quantum breakthrough.

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.

Aminoacyl-thiols reacting selectively with RNA diols over amine nucleophiles and demonstration of chemically controlled formation of peptidyl-RNA in water at neutral pH suggest an important role for thiol cofactors before the evolution of enzymes.

Florez Ariza and Lue et al. use cryo-electron microscopy to investigate how the RECQL5 helicase regulates transcription. Their structural findings suggest that RECQL5 can modulate RNA polymerase II’s translocation state, potentially restarting stalled transcription.

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.

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.

One approach to build a scalable quantum computer is to connect many smaller cells into a larger whole, but for realistic systems this quickly becomes prone to errors. Nickerson et al. present a noisy network protocol that can withstand high error rates within each cell but still perform stable purification.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

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.

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.

In this Viewpoint article, Nature Reviews Immunology invites 18 experts to discuss the nature of T cell exhaustion. How should T cell exhaustion be defined and what are the developmental relationships between exhausted T cell subsets? The contributors share their thoughts on key recent developments in the field.

JMML is an aggressive hematologic malignancy with myeloproliferative characteristics affecting young children. Here the authors report that C-type lectin-like molecule-1 (CLL-1) is upregulated in JMML and they develop CLL-1 CAR T cells showing in vitro and in vivo anti-JMML activity.

Metabolic liver disease is highly prevalent in subjects with obesity and involves inflammation, insulin resistance, and fibrosis, leading to cirrhosis. Here, the authors show the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and playing a major role in the pathogenesis of metabolic liver disease.

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.

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.

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.

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

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.

Senescence of metabolically active cells is a process linked to ageing. Here the authors reveal that CSB is required to block replicative senescence, and epigenetic control of CSB downregulation triggers proliferative arrest in a p21-dependent manner.

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.

Cooperative species of extrachromosomal DNAs are coordinately inherited through mitotic co-segregation.

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.

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.

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.

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.

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.

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.

Integrating remote sensing and eco-evolutionary theory, this study explains 80–84% of photosynthetic efficiency variation across ecosystems by incorporating plant traits such as chlorophyll and leaf longevity with climate data, highlighting the importance of these traits for global carbon modelling.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

This study develops a somatic molecular clock based on the accumulation of fixed somatic genetic variation that segregates among clonally produced organisms and applies it to the eelgrass Zostera marina.

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.

Random segregation of extrachromosomal DNA contributes to intratumoral heterogeneity and facilitates the rapid adaptation of human tumor cells to anticancer drugs.

The Congo Basin is home to the second largest stretch of continuous tropical forest, but the magnitude of greenhouse fluxes are poorly understood. Here the authors analyze gas samples and find the region is not actually a hotspot of N2O emissions.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Mismatch repair-deficient colorectal cancer clones adapt their mutation landscape by toggling homopolymer sequences in MutS homolog 3 (MSH3) and MutS homolog 6 (MSH6). This increases the subclonal mutation rate and clonal diversity, favoring immune escape and tumor growth.

Riboswitches can mediate ligand-dependent RNA cleavage and splicing to control gene expression. Here the authors present a method to functionally screen large libraries and identify functional variants.

While many tissues have been investigated for natural somatic mutations, human breast tissue has not been well studied. Here, the authors characterize somatic mutations in human breast tissue, finding effects of age and parity.

PrimPol is a multifunctional replicative enzyme that can bypass DNA damage, as well as reprime replication restart. Here, the authors have elucidated how PrimPol is recruited to stalled replication forks via specific interactions with RPA, which stimulates its primase activity.

Strong electron–electron interactions create a charge-density wave that modifies the topological state of the Weyl semimetal (TaSe₄)₂I. This implies the possibility of experimentally simulating axion electrodynamics in a solid-state material.

This protocol describes procedures for high-throughput analysis of trigenic interactions in yeast. Triple-mutant strains generated in a series of automated replica-pinning steps are grown on agar plates as individual colonies, and interactions are quantified with the trigenic synthetic genetic array scoring method.