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Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

The rapid dissociation of methanetetrol has been suggested as an impediment to its observation, despite the stability of its substituted derivative orthocarbonates. The authors identify methanetetrol as a product of carbon dioxide and water reactions in space-simulation experiments via photoionization mass spectrometry working in tandem with computation quantum chemistry.

Homogeneous Pt-group metal-based complexes make up the majority of C-H bond activation catalysts, but they are characterized by high cost and low abundance. Here, the authors report atomically dispersed titanium-aluminum-boron nanopowder for low-temperature catalytic activation of aliphatic C-H bonds via the element-specific cooperative mechanistic roles.

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

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

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.

Laboratory simulation experiments with isomer selective photoionization detection techniques reveal that octasulfur (S₈) and sulfanes can be easily formed in low temperature H₂S interstellar ice analogues exposed to ionizing radiation, suggesting a critical link between sulfur chemistry on ice coated nanoparticles in molecular clouds and the inventory of sulfur compounds in our Solar System.

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.

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.

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.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

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.

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.

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.

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.

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.

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.

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.

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 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.

Interstellar aldehydes are essential intermediates to form biomolecules necessary for the origins of life, but their formation mechanisms have remained elusive. Here, the authors elucidate the formation pathways of biologically relevant aldehyde, lactaldehyde, and its isomers in interstellar ice analogs composed of carbon monoxide and ethanol.

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.

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.

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.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

A pathway towards the formation of pyridine and (iso)quinoline, precursors to DNA and RNA, is revealed for conditions appropriate to Saturn’s moon Titan and the Taurus molecular cloud, providing insight into the synthesis of prebiotic molecules in space.

Alkylsulfonic acids represent an alternative source of sulfur for the origins of life. Here the authors demonstrate, via laboratory simulation experiments, the formation of these compounds in interstellar analog ices with implications for their incorporation into asteroids such as Ryugu.

Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.

Löhning and colleagues identify an alternative promoter for the Il1rl1 gene that drives IL-33 receptor expression in cytotoxic T cells and T-helper 1 cells

Despite being highly toxic, carbon monoxide (CO) is also essential as an intracellular signalling molecule, but CO-dependent signalling is poorly understood. Here, authors employ spectroscopic and electrophysiology methods and find that CO activates K_ATP channels via SUR2A, a heme-regulated receptor.

The authors here propose a chemical reaction that forms ammoniated phyllosilicates on Ceres. This process could trigger at a very low temperature, suggesting Ceres evolution in a region different from its current location.

Extraterrestrial sources may have provided prebiotic phosphorus to the early Earth. Here, the authors investigate the potential of phosphine-doped astrochemical analog ices to form phosphorus oxoacids as precursors to more complex prebiotic compounds.

Nanobowls represent building blocks of fullerenes and nanotubes as detected in combustion systems and deep space, but their formation mechanisms in these environments have remained elusive. Here, the authors explore the gas-phase formation of benzocorannulene and beyond to the C₄₀ nanobowl.

The reaction of benzyl radical self-reaction to anthracene opens-up a previously overlooked avenue for a more efficient synthesis of aromatic, multi-ringed structures via excited state dynamics in the gas phase.

The Strecker synthesis is considered a viable route to amino acids formation on the primordial Earth. Here the authors succeed in observing its elusive intermediate aminomethanol, formed by insertion of an electronically excited oxygen atom in methylamine and stabilized by an icy matrix, using isomer-selective photoionization time-of-flight mass spectrometry during thermal desorption of the ice mixture.

Helicenes represent key building blocks leading eventually to carbonaceous nanostructures. Here, exploiting [4]-helicene as a benchmark, the authors present a synthetic route to racemic helicenes via a vinylacetylene mediated gas phase chemistry with aryl radicals involving ring annulation.

Interstellar silicates play a key role in star formation, however their synthetic routes are not fully understood. Here, the authors provide evidence for the formation of SiO₂ along with SiO via low-temperature gas phase chemistry.

Memory B cells are important for protecting the host from pathogen rechallenge, but their properties and locations remain ill-defined. Here the authors show, using single-cell transcriptomics and repertoire analyses, that mouse spleen and bone marrow host distinct populations of isotype-switched memory B cells to potentially optimize for rapid recall responses.

High-nitrogen content polyhedral molecules are of fundamental interest for theory and for synthesis applications. The authors, using isomer selective, tunable soft photoionization reflectron time-of-flight mass spectrometry, identify the formation of a hitherto elusive prismatic P₃N₃ molecule during sublimation of PH₃ and N₂ ice mixtures exposed to energetic electrons.

Small polycyclic aromatic hydrocarbons (PAHs) are thought to be nucleation sites for the growth of Titan’s haze layers. Using laboratory experiments and electronic structure calculations, Zhao et al. show that small PAHs can by synthesized by rapid, barrierless reactions in Titan’s low-temperature environments.

Polycyclic aromatic hydrocarbons (PAHs) represent key molecular building blocks in extraterrestrial environments but the understanding of their formation and growth in this environment has remained elusive. Here the authors reveal how naphthalene can be efficiently formed via rapid radical–radical reactions.

Authors from the University of Heidelberg present a provocative and comprehensive Review of the issues involved in management of hypertension in patients with type 2 diabetic nephropathy. After examining the relationships between the renin–angiotensin system (RAS), proteinuria and hypertension, Ritz and Dikow focus on controversies such as the effect of RAS blockade beyond blood-pressure reduction, and optimal doses of drugs that inhibit RAS.

Pyrene, a polycyclic aromatic hydrocarbon composed of four fused benzene rings, is putatively a key molecule in the formation of 2D carbonaceous structures. Using experimental and computational techniques, Zhao et al. show that pyrene can form in circumstellar conditions.

The heterogeneity underlying cancer organoid phenotypes is not yet well understood. Here, the authors develop an imaging analysis assay for high throughput phenotypic screening of colorectal organoids that allows to define specific morphological changes that occur following different drug treatments.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.