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Based on a proteogenomic analysis, Perreault and colleagues report that the majority of predicted tumor antigens originate from unmutated genomic sequences in melanoma and non-small cell lung cancer.

SPP1+ macrophages and CD8 + exhausted T cells are known to crosstalk. Here, the authors discover that extrahepatic tumors facilitate liver metastasis by promoting the formation of an intermediate macrophage population in the liver that inhibits tumor-reactive CD8+ T cell function.

The photoinduced hidden metallic state in 1T-TaS₂ has so far been stabilized only at cryogenic temperatures. Now it is shown that accessing an additional mixed-phase long-lived metastable state can stabilize the hidden phase at higher temperatures.

Stabilizing charge density wave states in low-dimensional systems is challenging. Here, the authors stabilize an ordered incommensurate charge density wave at elevated temperatures via endotaxial synthesis of TaS₂ polytype heterostructures, where charge density wave layers are encapsulated within metallic layers.

Sinapate esters are promising nature-inspired sunscreen and antioxidant agents but their photoisomerization may lead to ineffective or harmful species. Here the authors propose a symmetric ester with indistinguishable trans and cis isomers and prove its effectiveness by optical spectroscopies on a skin mimic.

In plants, the shoot apical meristem generates all of the above ground organs and meristem morphology may predict important agricultural traits. Here Leiboff et al. use high throughput phenotyping and a genome-wide association study to uncover genes associated with variation in maize meristem size.

The HigBA toxin–antitoxin system of Caulobacter crescentus can act as a switch between promoting and inhibiting bacterial growth, depending on the dosage of HigA antitoxin, HigB toxin and its mRNA target.

There are many proposals for new forms of quantum matter in frustrated magnets but in practice disorder prevents the realisation of theoretically-tractable idealised models. Kimchi et al. show that recently observed scaling behavior common to several disordered quantum magnets can be understood as the emergence of a universal random-singlet regime.

There is a need to optimise cryo-EM data acquisition approaches to improve the resolution of GPCR cryo-EM structures to better than 2.5 Å, in order to use them for structure-based drug design purposes. Here, the authors present a systematic analysis of the main cryo-EM experimental parameters using three GPCRs as test cases, which is also of interest for the cryo-EM structure determination of other small membrane proteins.

The authors present an in-depth investigation of excited state dynamics and molecular mechanism of the voltage sensing in microbial rhodopsins. Using a combination of spectroscopic investigations and molecular dynamics simulations, the study proposes the voltage-modulated deprotonation of the chromophore as the key event in the voltage sensing. Thus, molecular constraints that may further improve the fluorescence quantum yield and the voltage sensitivity are presented.

Chemotherapeutic agents targeting thymidylate biosynthesis, and particularly the enzyme thymidylate synthase, have now been key cancer therapies for 60 years. In this article, the classic and novel approaches to targeting this metabolic pathway and strategies for overcoming drug resistance mechanisms are comprehensively reviewed.

The primary challenge in commercializing perovskite solar cells stems from the fragile and moisture-sensitive nature of perovskite materials. Here, authors propose a multi-functional asynchronous cross-linking strategy and achieve high-performance and stable devices with mere 0.30 voltage deficit.

Some quantum spin liquids are expected to have an effective Fermi surface of fractionalized spinon excitations. The two-dimensional spin liquid candidate 1T-TaSe₂ has charge density modulations that may be caused by an unstable spinon Fermi surface.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Anti-cancer fluoropyrimidine drugs have antibacterial effects on the gut microbiome, and these drugs can be metabolized by gut bacteria via conserved pathways also found in mammalian hosts.

Mutations in mtDNA contribute to mitochondrial disease and aging only if they rise in abundance. Here, the authors show that deleterious mutations reach high abundance by hitchhiking on genomes that have a replicative advantage.

Neodymium isotopes are tracers for past and present ocean circulation and biogeochemistry. Here, the authors combine observations of neodymium and radium isotopes in the Amazon estuary and show that the rapid release of neodymium from river suspended sediments leaves a strong imprint on coastal sea water.

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 causes of the Upper Pleistocene megafauna extinction in Australia and New Guinea are debated, but fossil data are lacking for much of this region. Here, Hocknull and colleagues report a new, diverse megafauna assemblage from north-eastern Australia that persisted until ~40,000 years ago.

Volumetric muscle loss leads to functional muscle impairment, and current stem cell-based treatments show limited efficacy. Here, the authors generate a stem cell scaffold, implant it in mice, and show that an exercise regimen enhances innervation and restoration of muscle function in mice.

MicroRNAs are exciting new regulators of genes involved in cell growth and development. Regulatory roles for microRNAs have been identified in plants and animals, but these tiny regulators have not been found in bacteria or fungi. Here, Sarnow and colleagues discuss the fascinating roles of both virus- and host-cell-encoded microRNAs in virus lifestyles.

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.

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.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Unconventional quasiparticles carrying spin but not electric charge emerge in quantum spin liquid phases. The Kondo interaction of these spinon quasiparticles with magnetic impurities may now have been observed.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Clean energy can provide different health and environmental benefits depending on location. Modelling shows that renewable energy and energy-saving projects could deliver annual benefits of up to US$210 million across six locations in the USA.