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Class A and B GPCR show differential downstream regulation and functions. Here, the authors show how their C-termini largely mediate GRK-specific β-arrestin N-domain conformational changes and co-internalization, while GPCR helix-bundles govern pERK.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Liquid-liquid phase separation (LLPS) is known to modulate the pathological aggregation of proteins implicated in neurodegenerative diseases, such as tau and TDP-43, but the phase behavior of the tau/TDP-43 multicomponent system remains underexplored. Here, the authors show that, depending on protein concentration and the strength of LLPS-driving interactions, tau and TDP-43 low complexity domain (LCD) can function either as scaffolds — driving condensate formation — or as clients — being passively recruited into condensates formed by the other.

The spatial single-cell multiomic atlas of the first trimester human placenta at molecular resolution provides a blueprint for future studies on early placental development and pregnancy.

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

The two-dimensional structure of graphene is known to impart high strength, but can be hard to synthesize without grain boundaries. Here, the authors find that strength increases with grain boundary mismatch, which results from low atomic-scale strain in the carbon–carbon bonds at the boundary.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In their study, Dorman and Bendoumou et al., reveal a post-transcriptional regulation of unspliced HIV-1 RNA by host factors MATR3, MTR4, and the viral protein Rev, identifying a previously uncharacterized post-transcriptional block in nucleocytoplasmic export, which plays a crucial role in HIV-1 latency and reactivation.

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.

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.

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.

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.

Federated learning, a method for training artificial intelligence algorithms that protects data privacy, was used to predict future oxygen requirements of symptomatic patients with COVID-19 using data from 20 different institutes across the globe.

In this study, Kagan et al. highlight the relevance of adequate cardiolipin homeostasis by offering mechanistic insight into the pathogenesis of Barth syndrome. The study shows how altered accumulation of mono-lyso-cardiolipin, one of the derivatives of the mitochondrial lipid cardiolipin, forms an anomalous peroxidase complex with cytochrome c, thus leading to increased oxidation of polyunsaturated phospholipids.

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.

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.

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.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

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.

Although plant functional trait combinations reflect ecological trade-offs at the species level, little is known about how this translates to whole communities. Here, the authors show that global trait composition is captured by two main dimensions that are only weakly related to macro-environmental drivers.

Susceptibility to ferroptosis can be modulated by nitric oxide (NO^•) and NO synthase iNOS and through enrichment of activated M1 macrophages. NO inhibits the lipoxygenase 15-LOX that drives production of pro-ferroptotic lipids in macrophages.

Genetic screening identifies a rich catalogue of regulators of micronucleus formation.

Genome-wide association analyses, functionally informed fine-mapping and complementary gene prioritization approaches identify new risk loci and candidate effector genes for CAD.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

In a substudy of the RATE-AF trial, which compared heart rate control therapy using digoxin or the beta-blocker bisoprolol, heart rate and physical activity data collected using a wearable device showed equivalent heart rate control by the two drugs and could be used to predict future heart failure functional class as well as standard clinical measurements.

Reduced expression of DICER—responsible for the processing of microRNA precursors—was previously linked to poor clinical outcomes in cancer patients. Here, the authors uncover an epigenetic mechanism by which hypoxia suppresses DICER expression and deregulates the miR-200-Zeb1 circuit in breast cancer to promote the tumour phenotype.

The largest whole-exome sequencing study of sporadic congenital hydrocephalus identities mutations associated with disrupted fetal neuro-gliogenesis as the primary pathophysiological event in a significant number of cases.

Turrell et al. show that, in young mice, low-level PDGF-C expression maintains dormancy of disseminated tumor cells, but, in aged or fibrotic lungs, the PDGF-C-high environment promotes proliferation, which can be counteracted with inhibition of PDGFRα or PDGF-C blockade.

In a global grassland dataset, large mammalian herbivores rescued forb cover and diversity from the negative effects of eutrophication.

Global patterns of regional plant diversity are relatively well known, but whether they hold for local communities is debated. This study created multi-grain global maps of alpha diversity for vascular plants to provide a nuanced understanding of plant diversity hotspots and improve predictions of global change effects on biodiversity.

Reconfigurable materials are of interest for many photonic applications. Here, Montelongo et al. demonstrate optical elements such as Bragg diffraction gratings, volumetric photonic crystals, lenses, and holograms in a composite with dispersed nanoparticles which can be recorded and erased.