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Fibrodysplasia ossificans progressiva is a severe disorder characterized by heterotopic ossification, and is caused by mutations in ACVR1. Here, the authors show that expression of mutant ACVR1 in fibro/adipogenic progenitors recapitulates disease progression, and that this can be halted by systemic inhibition of activin A in mice.

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.

Persistent infections force the host to develop compensatory mechanisms to prevent organ damage, which are collectively called disease tolerance. Here authors show in a Pseudomonas aeruginosa murine infection model that an alginate-itaconate metabolic interplay, creating metabolic synchrony between the host and the pathogen plays a role in mitigating harmful inflammation.

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).

Rare earth element (REE) extraction and separation are crucial for sustainable resource management, yet efficient methods remain limited. Here, the authors append macrocyclic chelator BZmacropa to a solid resin and demonstrate selective REE extraction and separation with high purity and recyclability, offering a promising solution for REE recovery from complex mixtures and waste streams.

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.

Loss-of-function mutations in Myosin Binding Protein C3, MYBPC3, are the most common genetic cause of hypertrophic cardiomyopathy. Here, the authors present an AAV9-based gene therapy system with an optimized expression cassette with minimal promoter and cis-regulatory elements that can ameliorate cardiac functions and prolong survival in a murine MYBPC3-deficient model.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

The physical implementation of quantum information processing requires individual qubits and entangling gates. Here, the authors demonstrate a modular implementation through chemistry, assembling molecular {Cr₇Ni} rings acting as qubits, with supramolecular structures realizing gates by choice of the linker.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Gas sorption and separation in porous materials is dependent on the host–guest binding within any given system. Now, the molecular details of cooperative binding between small hydrocarbons and a metal–organic framework, NOTT-300, at multiple sites have been elucidated by complementary scattering and diffraction techniques. This material is also capable of separating C₁ and C₂ hydrocarbons under ambient conditions.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Allogeneic hematopoietic stem cell transplantation restores the whole hematopoietic compartment of the recipient, but some cell types, such as Type II innate lymphoid cells (ILC2) are not reconstituted efficiently. Here authors show that ILC2s could be converted to ILC1-like cells in the mouse small intestine post-transplantation, which might contribute to the lower than physiological ILC2 numbers.

Complete blood count indices are tightly regulated around setpoints for decades in healthy adults, and represent a deep phenotype providing opportunities for investigating differential disease risks, improving clinical care and advancing precision medicine.

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.

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.

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.

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.

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 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.

Stable chelation of the ¹⁴⁷Pm radionuclide in aqueous solution by the newly synthesized organic diglycolamide ligand is demonstrated and the resulting complex studied, showing accelerated shortening of bonds at the beginning of the lanthanide series.

Naturally occurring bromine- and iodine-containing compounds substantially reduce regional, and possibly global, tropospheric ozone levels. Experimental and model results suggest that the reaction of ozone with iodide could account for around 75% of observed iodine oxide levels over the tropical Atlantic Ocean.

Mutations in the ARID1B subunit of the BAF chromatin remodeling complex are associated with the neurodevelopmental Coffin-Siris syndrome. Here the authors reveal that there is a transition from ARID1A-containing complexes to ARID1B during cranial neural crest cell differentiation that is impaired in Coffin-Siris patient-derived cells, which is important for exit from pluripotency.

Enabled by augmented muscle afferents, a bionic leg under continuous neural control restores biomimetic adaptations to various walking speeds, terrains and perturbations.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Auxin-driven transcriptional responses are mediated by ARF transcription factors. Here the authors characterize an F-box protein, AFF1, that regulates the accumulation, condensation, and nucleo-cytoplasmic partitioning of ARF19 and ARF7.

Amino acid biosynthetic pathways are an attractive alternative to treat chronic infections such as Mycobacterium tuberculosis (Mtb). Here, the authors investigate the metabolic response to disruption of the aspartate pathway in persistent Mtb and identify essential enzymes as potential new targets for drug development.