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It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

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

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.

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.

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 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.

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.

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.

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.

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.

G protein-coupled receptors are a large family of signalling proteins that mediate cellular responses primarily via G proteins or arrestins, and they are targets of one-third of the current clinically used drugs; here, an active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin-1 is determined, revealing unique structural features that may constitute essential elements for arrestin-biased signalling.

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.

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.

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.

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 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.

Here, the authors report structures of corticotropin releasing factor receptor 2 (CRF2R) bound to agonist Urocortin 1 (UCN1) and coupled to G proteins G₁₁ and G_o, offering insight into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

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.

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.

Cryo-electron microscopy structures of three different serotonin receptors in complex with serotonin and other agonists provide insights into the role of lipids in regulating these receptors and the structural basis of ligand recognition.

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.

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.

Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of inflammatory diseases. Here authors report a cryoelectron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, which provides insights into PACAP27 binding and VIP receptor activation.

An antibody against the pituitary hormone Fsh reduces adiposity and increases thermogenesis in ovariectomized mice or mice fed a high-fat diet.

Folate receptor-α (FRα) is overexpressed in many cancer cells and is therefore an important therapeutic target: here the X-ray crystal structure of folate-bound FRα is presented, revealing details of the ligand-binding pocket that may be useful in the development of small-molecule inhibitors for anticancer therapy.

The fourteen members of the PYR/PYL family are receptors for the plant hormone abscisic acid (ABA). Now structural and functional work using the synthetic ligand pyrabactin, which inhibits seed germination, reveal that the PYL/PYR receptors respond differently to pyrabactin, elucidate the mechanisms for selective activation or inhibition of ABA receptors and allow the design of novel agonists.

The plant hormone abscisic acid (ABA) is a regulator of plant growth, development and responses to environmental stresses. Recently, the PYR/PYL/RCAR family of START proteins was found to bind ABA and mediate inactivation of downstream effectors. The crystal structures of apo and ABA-bound receptors as well as a ternary PYL2–ABA–PP2C complex is now reported and analysed, revealing a gate–latch–lock mechanism underlying ABA signalling.

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.

The voltage-gated sodium channel Na_v1.7 has a dual role in osteoarthritis—in chondrocytes, it promotes joint damage, and in dorsal root ganglia neurons, it increases pain transmission.

Formylpeptide receptors (FPRs) are a class of chemotactic G protein-coupled receptors (GPCRs) that recognize pathogen- and host-derived formylpeptides. Here the authors report the 3.17 Å cryo-EM structure of the human FPR2-G_i signaling complex with a bound peptide agonist and in combination with computational docking and MD simulations provide mechanistic insights into formylpeptide recognition by FPRs.

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.

Catalytically inactive DNMT3B3 is crucial in de novo CpG methylation of DNA, interacting with the nucleosome core to orient catalytically active DNMT3A2 so that it can bind to nearby linker DNA.

The cryo-electron microscopy structure of human rhodopsin bound to the inhibitory G_i protein-coupled receptor provides insights into ligand–receptor–G-protein interactions.

Previous work has shown in iPSC derived neurons that synaptic impairments are associated with a 4bp DISC1 deletion. Here the authors demonstrate a role for the PDE4 signalling pathway in these synaptic impairments.

Pentatricopeptide repeat (PPR) proteins are involved in different RNA processes, but how they recognize their target RNAs has been unclear. Now crystal structures of plant PPR protein–THA8 in complex with RNA, along with functional analyses, reveal an asymmetric THA8 dimer with RNA bound at the dimeric interface.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Ion-selective membranes are widely used for water purification and electrochemical energy devices but designing their pore architectures is challenging. Membranes with narrow channels and hydrophilic functionality are shown to exhibit salt ions transport and selectivity towards small organic molecules.

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

Plants respond to abiotic stress via the phytohormone ABA. Here, Cao et al. report a series of new ABA receptor agonists, named AMFs, which have higher receptor-binding affinities and show that, when employed in tandem with ABA receptor overexpression, can significantly increase drought resistance