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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.

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.

Premalignant stromal cells from women with germline BRCA1 mutations exhibit increased expression of secreted factors regulating epithelial homeostasis in a paracrine fashion. These secreted factors, such as MMP3, promote premalignant epithelial changes including elevated proliferation and altered differentiation of a subpopulation of luminal progenitor cells.

The human plasma lipidome captures risk for cardiometabolic diseases. Here, the authors perform univariate and multivariate genome-wide analyses of 179 lipid species in 7174 Finnish individuals, revealing genetic links between diseases and lipid species beyond the standard lipids HDL-Cholesterol, LDL-Cholesterol, Triglycerides, and total Cholesterol.

Deconfined quantum phase transitions go beyond traditional paradigms. Here the authors reveal an unconventional dual asymmetric Kibble-Zurek scaling in the critical dynamics near the deconfined multicritical point with multiple length and time scales.

The molecular composition of the cellular lipidome is complex and still poorly understood. The exact mechanisms of how compositional complexity affects cell homeostasis and its regulation are also unclear. The emerging field of lipidomics is developing sensitive mass spectrometry technologies for the quantitative characterization of the lipidome.

Mutations near the ORMDL3 gene have been associated with childhood asthma. Here, in yeast, Orm proteins are shown to function in sphingolipid homeostasis; alterations in this control result in misregulation of sphingolipid production and accumulation of toxic metabolites. This raises the testable hypothesis that misregulation of sphingolipids may directly contribute to the development of asthma.

Addition of a multifunctional ionic additive in mixed two-dimensional–three-dimensional bromide/chloride perovskites enables efficient blue perovskite LEDs with external quantum efficiency of up to 21.4% and half-lifetime of 129 min at an initial luminance of 100 cd m^–2.

Lightning Pose is an efficient pose estimation approach that requires few labeled training data owing to its semi-supervised learning strategy and ensembling.

Mitometer enables efficient, rapid, and accurate automated segmentation and tracking of mitochondria from time-lapse images. Mitometer performs well on diverse input images and can be used to monitor dynamic fission and fusion events.

The onset of eco-evolutionary dynamics marks a stepping stone in the transition from chemistry to biology. Now a minimal replicator system showing such dynamics has been developed. The replicators adapt to changes in their environment that they themselves induced through photoredox catalysis.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

There is an urgent need for biomarkers for type 2 diabetes progression that provide a deeper understanding of the disease process. Here, the authors identify biomarkers in three molecular classes, replicate them in other cohorts and explore top protein biomarkers in detail in functional studies.

The exact drivers for the end-Permian mass extinction remain controversial. This study reveals a turning point with the exhaustion of the terrestrial input and a strong fertilization of the marine realm leading to the demise of marine ecosystems.

Brain genetic co-expression networks pinpoint specific, convergent synaptic pathways—rather than the complement system—through which genetic variation at the C4 locus imparts risk for schizophrenia.

Wigger, Barovic and Brunner et al. perform a multidimensional analysis of islets from metabolically characterized patients who had undergone pancreatectomy, observing remarkable heterogeneity between samples from individuals with type 2 diabetes, thus arguing against models of linear beta-cell dedifferentiation in diabetes.

Nonreciprocity is viewed as a useful feature for many future optical devices. Here, the authors observe all-optically-induced nonreciprocal dichroism in monolayer WS2, which is explained by valley-selective response.

RNA modifications represent a critical aspect of RNA biology that is not well suited to sequencing methods. Here, the authors provide a software tool for automated analysis of RNA tandem mass spectra with full support of modifications, isotope labelling, and control of false discovery rate.

Arteries are vital blood vessels for our body and their growth and patterning are critical for proper blood flow. Here they use a retina model to show that a balance of EphB4 receptor and ephrin-B2 ligand integrate a well-wired molecular network to control arteriovenous patterning and vascular growth.

Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

The valley pseudospin of electrons may serve as an additional degree of freedom for future on-chip low-energy signal processing. Now, a nanophotonic circuit that integrates a monolayer of WS₂ routes valley indices unidirectionally via the chirality of the photons.

Zhang et al. report that the BLA contains ‘hardwired’ positive-valence and negative-valence neurons, which each express Fezf2 but have distinct connectivity. These neurons separately drive learning and expression of avoidance or approach behavior.

The integration of replication with metabolism represents a key step in the transition of chemistry into biology. Now, it has been shown that a self-replicator can recruit and activate two different photocatalytic cofactors, which then catalyse the synthesis of the precursors for the replicator.

The diversity of fibroblasts contributing to wound healing is unclear. Here, the authors use single-cell RNA-sequencing to identify heterogeneity among murine fibroblasts in the wound and find that recruited myeloid cells contribute to adipocyte regeneration during healing.

Caveolae are highly abundant, but enigmatic, specialized membrane structures in mammalian cells. What might the function of these specialized domains be? Caveolae function as carriers in the exocytic and endocytic pathways, but have also been implicated in signalling, mechanosensing and lipid regulation.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Although considerable efforts have been made to deliver drugs to particular tissues, little is known about targeting drugs to specific cellular compartments. By examining the fundamental principles of membrane trafficking and subcellular organization, the authors outline strategies to increase drug concentrations specifically in the relevant subcellular locations.

Singlet fission — the conversion of one singlet exciton into two triplet excitons, could improve the efficiency of photovoltaic devices — but its mechanism is still to be fully understood. Now, in films of TIPS-tetracene, it has been shown that the formation of the triplet pair state, which has been proposed to mediate singlet fission, is ultrafast and vibronically coherent in this endothermic fission system.

A high-throughput screen of preclinical, investigational and FDA-approved drugs identifies compounds that possess antiviral and neuroprotective effects against Zika virus infection in human neural progenitor cells and astrocytes.