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Multi-layer film packaging revolutionized food preservation by combining diverse material layers to optimize barrier properties, mechanical strength, and shelf-life but they pose significant recycling challenges due to their structural complexity. This perspective examines key structure-property relationships governing barrier performance and highlights innovations in material design.

High-pressure measurements of the electrical conductivity of (Mg,Fe)O, used as an analogue for basal magma ocean material, indicate that the conductivity is high enough to produce a dynamo much stronger than a core-driven dynamo for super-Earths larger than 3–6 Earth masses.

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).

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.

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.

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

The properties of materials can be drastically modified under extreme pressure. Here the authors investigate ramp-compressed sodium to 5 million atmospheres with in situ X-ray diffraction and optical reflectivity, revealing a complex temperature-driven polymorphism and suggesting the formation of a previously predicted electride phase.

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.

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 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.

Protein complexes consisting of a cyclin-dependent kinase (CDK4 or CDK6) and cyclin D control passage through the G1 checkpoint of the cell cycle by phosphorylating the retinoblastoma (RB) protein¹. The ability of these complexes to phosphorylate RB is inhibited by a family of low molecular weight proteins including p16^INK4a (refs 2,3), p15^iNK4B (ref 4)? and p18 (ref 5) Germline mutations in the p16^INK4a gene have been identified in approximately half of families with hereditary melanoma^6–12. In this report, we describe an Arg24Cys mutation in CDK4 in two unrelated melanoma families which do not carry germline p16^INK4a mutations6. This mutation was detected in 11/11 melanoma patients, 2/17 unaffecteds and 0/5 spouses. The CDK4-Arg24Cys substitution has previously been identified as a somatic mutation in a melanoma that gives rise to a tumour-specific antigen recognized by autologous cytolytic T lymphocytes¹³. This mutation has a specific effect on the p16^INK4a binding domain of CDK4, but has no effect on its ability to bind cyclin D and form a functional kinase¹³. Therefore, the germline Arg24Cys mutation in CDK4 generates a dominant oncogene that is resistant to normal physiological inhibition by p16^INK4a. The only previous example of a dominant oncogene transmitted in the human germline is the RET gene that gives rise to MEN2A^14,15 and MEN2B¹⁶.

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.

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.

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.

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.

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.

Cytotoxic cancer therapy can induce accelerated growth of surviving cancer cells, a phenomenon known as tumor repopulation. This report uncovers a mechanism by which caspase 3 activation in treated cells promotes growth of surviving cells, mediated by iPLA₂ and PGE₂. The level of caspase 3 activation in human tumors also correlates with risk of relapse, suggesting that this pathway may be a determinant of therapeutic effects.

A subset of pediatric gliomas harbour alterations in fibroblast growth factor receptor (FGFR)-family proteins. Here, the authors characterise the genomic landscape of 11,635 gliomas across ages and use isogenic model systems to explore the underlying biology of FGFR1-altered gliomas and potential therapeutic vulnerabilities.

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.

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.

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.

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 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 rare protein-truncating, damaging missense and copy number variants from exome sequencing of 63,237 individuals identifies 72 genes associated with autism spectrum disorder.

Nie et al. describe a mechanism underlying the degradation of the histone methyltransferase NSD2 through the recruitment of FBXO22 E3 ligase, providing a chemical probe for NSD2 function study and targeted protein degradation.

The Microprocessor executes the first step in microRNA biogenesis. Here, the authors identify a protein motif in DGCR8/Pasha that is essential for proper Microprocessor assembly, which in turn regulates its subcellular localization.

Paul Boutros, Robert Bristow and colleagues report a molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer. They find that multifocal tumors are highly heterogeneous, and they identify a novel recurrent amplification of MYCL1.

In a multicenter, single-arm, open-label phase 2 study of patients with previously treated metastatic uveal melanoma, treatment with tebentafusp, a soluble TCR bispecific (gp100xCD3) showed promising clinical activity with an acceptable safety profile.

Genomic analyses of localized, non-indolent prostate cancer identify recurrent aberrations that can predict relapse, and also highlight differences between early prostate cancer and metastatic, castration-resistant disease.

The signaling-specific inhibitor AEF0117 selectively inhibits CB₁ activation by THC and reduces self-administration and subjective effects of cannabis in clinical trials, making it a potential treatment for cannabis use disorder.