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Fungal diseases threaten crops worldwide. By resolving the cryo-EM structure of fungal succinate dehydrogenase, researchers designed an inhibitor with broad antifungal activity, strong field performance, and reduced environmental toxicity.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Head and neck cancer patients could greatly benefit from personalised treatment, but a lack of large public datasets hampers this potential. Here, the authors present HANCOCK, a multimodal dataset that integrates demographical, clinical, and histopathological data for 763 head and neck cancer patients that empowers machine learning models for clinical outcome prediction.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

The induction of immunogenic cell death (ICD) can potentiate antitumour immunity. Here the authors show that USP18, a negative regulator of IFN signaling protects cancer cells from ICD by suppressing the expression of canonical and non-canonical IFN-stimulated genes.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Many host structures are vital for viral infection and the endoplasmic reticulum (ER), in particular, is essential. In this Review, Tsai and colleagues highlight examples of subversion of the ER by diverse viruses to promote all stages of their life cycle, from entry to egress.

The authors develop multimodal machine learning models to infer metastatic recurrence risk for early-stage, hormone receptor-positive breast cancer from H&E images using >6000 cases across three centers, outperforming a nomogram and unimodal methods.

Ferrimagnets possess multiple spin sub-lattices resulting in a complex magnon band structure and subtle spin transport across interfaces. Here, the authors show how the spin Seebeck effect, the thermal generation of pure spin current, may be an effective tool to study these magnetic excitations.

Endoplasmic reticulum (ER) stress is induced following the accumulation of unfolded proteins in the ER. This triggers the unfolded protein response, which initially acts to compensate for damage, but if prolonged or excessive can trigger cell death. Here, Reed and colleagues discuss the role of ER-initiated cell death pathways in diseases including neurodegeneration, hypoxia, heart disease, diabetes and immune disorders, while identifying promising therapeutic targets.

Recent studies of mRNA distribution and translation show that, in addition to serving as the site of protein translocation into the endoplasmic reticulum (ER), ER-bound ribosomes translate a large fraction of mRNAs that encode cytosolic proteins. This, along with the discovery of many mechanisms for recruiting translation to the ER, suggests an expansive role for the ER in post-transcriptional gene expression.

Radiation and conduction are generally considered as the main energy transport mechanisms for the evolution of early supernova remnants. Here the authors experimentally show the role of electron heat transfer on the growth of Rayleigh–Taylor instability in young supernova remnants.

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.

The unfolded protein response pathway that is induced by endoplasmic reticulum (ER) stress has important roles in immune cell development and function, which have led to new insights into the pathogenesis of inflammatory diseases.

Recent studies of the early secretory pathway have analysed cargo selection and transport-carrier formation by components of the endoplasmic-reticulum-associated coat protein complex-II (COPII). Results are indicative of a unifying model of cage and coat function in vesicle and tubule formation as well as fission in endomembrane traffic.

The protein stability of KRAS mutants can influence tumor promotion. Here, the authors identify that deubiquitinase JOSD2 stabilizes KRAS mutants and JOSD2 depletion inhibits KRAS-mutant colorectal cancer growth in part due to mutant KRAS degradation.

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.

Mitochondrial metabolism is essential for the dynamic regulation of cardiac and vascular tissues, and the relevance of basic mitochondrial biology in cardiovascular disease is being increasingly recognized. In this Review, the authors explore the physical interaction between mitochondria and sarco/endoplasmic reticulum, discussing how the communication between these two organelles is involved in cardiovascular pathologies.

The unfolded protein response (UPR) is an important pro-survival pathway that is often activated in tumour cells owing to endoplasmic reticulum stress that is caused by both intrinsic and extrinsic factors. Wang and Kaufman discuss the mechanisms of UPR activation in tumour cells, the importance of this pathway to cancer development and targeting strategies for therapeutic intervention.

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.

Using JWST, more than 40 individual stars have been detected in a distant galaxy, dating back to when the Universe was only half of its current age. The stars appear to be red (super)giants that are magnified by factors of hundreds.

Superconductivity at temperatures approaching 40 K for a hole-doped nickel oxide that is isostructural with cuprate superconductors demonstrates the existence of a broader family of materials and potential for achieving higher-temperature superconductivity.

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.

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.

In recent years a new concept of immunogenic cell death (ICD) has emerged. In this Review, the authors discuss the role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and how this might relate to therapeutic intervention.

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.

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.