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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.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

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.

Heat increases heart rate across vertebrates. Here, authors pinpoint a motif in the HCN4 channel that governs heat-driven heart rate acceleration and demonstrate its conserved role in other HCN channels, revealing a conserved mechanism linking temperature to membrane excitability.

This study reveals that water availability at the wound determines plant regeneration outcomes. High water availability induces root regeneration whereas low water availability triggers callus formation via stress hormones that shape auxin response maxima to activate distinct regeneration pathways.

Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The pupil is known to assist retinal adaptation to light level changes. Here, the authors find a mechanism for how the pupillary light reflex drives monocular and binocular retinal activity in mice and shapes conscious visual perception in humans.

Three-dimensional nanofabrication allows for the precise tailoring of curvature of magnetic nanowires, and therefore the local symmetry breaking. Here, Ruiz-Gomez et al use this control to study the interaction of domain walls with local curvature, engineering potential wells and shift registers.

In this study, the authors provide a global overview of SARS-CoV-2 genome sequencing, and estimate the proportion of cases sequenced and time to genome upload. They identify disparities and highlight the need to strengthen surveillance in lower and middle income countries.

Organ-like 3D cultures are advanced model system for biology and medicine limited by their uncontrolled cell self-assembly. Here, the authors develop a hydrogel-in-hydrogel bioprinting approach to dynamically control the growth landscape of a broad range of living 3D cell cultures.

Patients with Huntington’s disease carrying the FAN1 R507H mutation have earlier than predicted onset of motoric symptoms. This study provides mechanistic insight into the interactions that may promote CAG repeat expansion. FAN1 R507 interacts with PCNA D232 and this interaction is impaired for FAN1 R507H, resulting in reduced FAN1 activity.

Decades of experience must inform future initiatives, urge Gabriel Chan and colleagues.

Here, Lax et al characterise the role and distribution of an epigenetic mark, adenine methylation (6mA), in the genomes of early diverging fungi and find the enzymes that write symmetric and asymmetric 6mA in their DNA.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Hydrogel force sensors directly bioprinted into embryonic tissues quantify the forces driving tissue remodelling and reveal the existence of mechanisms that counteract tissue morphogenesis.

Anlló et al. show that context effects on reward value encoding are found across 11 diverse countries, suggesting that this may be a basic feature of human decision-making.

Genetic and environmental factors impact on lung function, important in the diagnosis of pulmonary diseases. Here the authors use imputation of genotypes to the 1000 Genomes Project reference panel to identify novel, low frequency variants associated with lung function.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Human behaviour is complex and multifaceted, and is studied by a broad range of disciplines across the social and natural sciences. To mark our 5th anniversary, we asked leading scientists in some of the key disciplines that we cover to share their vision of the future of research in their disciplines. Our contributors underscore how important it is to broaden the scope of their disciplines to increase ecological validity and diversity of representation, in order to address pressing societal challenges that range from new technologies, modes of interaction and sociopolitical upheaval to disease, poverty, hunger, inequality and climate change. Taken together, these contributions highlight how achieving progress in each discipline will require incorporating insights and methods from others, breaking down disciplinary silos.

Gebhardt and colleagues developed a computational method using a naïve Bayes classifier to identify optimal protein labelling sites. Their analysis of 100+ proteins revealed four predictive parameters, leading to a Python package and a web-tool for protein structure analysis and labelling score calculations.

Following a wide-ranging review of studies, reports and policies about nature’s multiple values, combinations of values-centred approaches are proposed to improve valuation of nature, address barriers to uptake in decision-making, and make transformative changes towards more just and sustainable futures.

This study finds that U.S. vehicle assembly plants that have fully transitioned from gas engine to electric vehicle assembly have required higher labor intensity. It suggests that more, not fewer, workers are needed for electric vehicle assembly.

The regulatory mechanisms governing peptidoglycan-degrading autolysins remain poorly understood. In this work, Alvarez et al. show that lytic transglycosylase activity is inhibited by LD-crosslinks in Vibrio cholerae and other bacteria, providing resistance against predatory enzymes of both bacterial and viral origin.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

EF-G drives ribosomal translocation along mRNA. Time-resolved cryo-EM captured translocation with EF-G•GTP—without inhibitors—revealing how EF-G uses ribosome fluctuations to drive translocation and GTP hydrolysis to leave at the right moment.

A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patients with high-risk clear cell renal cell carcinoma.

Using meta-analysis of previous genome-wide association studies against the latest reference variant databases, this work identifies five new risk loci for glioblastoma and non-glioblastoma type of glioma.