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Icosahedral carboranes have long been considered to be aromatic but the extent of conjugation between these clusters and their substituents is still being debated. Here the authors demonstrate carboranes as conjugated bridges in optical functional chromophores.

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

The recognition of the mRNA codon by the tRNA anticodon is crucial for protein synthesis. Here the authors introduce non-standard nucleotides in bacterial and eukaryotic mRNA to reveal the minimal hydrogen bond requirement of codon-anticodon interaction for efficient and accurate translation.

Controlling light at scales smaller than its wavelength is attractive to manipulate light using small device footprints. Here, the authors propose a scheme to modify light on such small scales using a combination of metamaterial nanocavities coupled to nonlinear semiconductor heterostructures.

Interaction between Cooper pairs and other collective excitations may reveal important information about the pairing mechanism. Here, the authors observe a universal jump in the phase of the driven Higgs oscillations in cuprate thin films, indicating the presence of a coupled collective mode, as well as a nonvanishing Higgs-like response at high temperatures, suggesting a potential nonzero pairing amplitude above Tc.

Physical activity has the potential to combat the negative mental health effects of social isolation. Its benefit is particularly high in people at increased neural and psychological risk for affective disorders.

The lysosomal enzyme beta-glucocerebrosidase is a key player and promising therapeutic target in Parkinson’s disease. Here, Dobert et al. leveraged cryo-EM to solve the protein structure of the enzyme in complex with its lysosomal transporter LIMP-2.

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.

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.

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.

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.

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.

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.

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.

In an experimental multicopy plasmid evolution system that allows manipulation of mutation rate and copy number, low copy number promoted enrichment of beneficial alleles whereas high copy number maintained allelic diversity.

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 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.

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.

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.

Adenosylcobalamin is a form of vitamin B₁₂ that serves as a coenzyme in different reactions and as a ligand for riboswitches to control bacterial gene expression. The crystal structure of a B₁₂ riboswitch from Symbiobacterium thermophilum bound to its ligand adenosylcobalamin is now presented, revealing the determinants for ligand recognition and gene expression control.

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.

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.

In this paper and the related paper from Lugli and colleagues the authors show that high levels of NaCl inside the tumor have a beneficial effect on CD8⁺ T cells and their ability to control tumor growth as a result of enhanced T cell receptor activity.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

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.

On-chip synthesis and screening has been used to automate drug discovery but on-chip analysis still remains a major limitation. Here, the authors report on a dendrimer-based surface patterning method to create nanodroplet arrays on materials which allow for on-chip high-throughput analysis.

In vitro blood-brain barrier (BBB) models do not fully recapitulate the in vivo barrier function. Here the authors develop an organ-on-a-chip BBB model using iPS-derived human brain endothelial cells differentiated under hypoxia, primary human pericytes and astrocytes, which maintains in vivo-like BBB barrier and shuttling functions for a week.

High-throughput cell-based screening of compound libraries is utilised in drug development; however, a lack of compatible methods limits direct synthesis and testing. Here, the authors present a diverse chip based synthesis system which can be combined with cell screening and demonstrate the application.

The TcA component of Photorhabdus luminescens ABC-type toxin complexes forms a transmembrane pore and injects TcC, the functional component of the toxin, into the target cell by means of a syringe-like mechanism.

Here authors show that GDF15, a cytokine that is produced by cancer cells, prevents T cells from extravasation into the tumour microenvironment. Low availability of T cells in GDF-15-expressing tumours thus precludes effective immune therapy.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.