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From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

The authors synthesize bee assemblage data from 681 crop fields across three continents, finding that local pesticide hazards and decreasing adjacent semi-natural habitats both negatively affected wild bee abundance and species richness in crop fields, while pesticides also reduced functional diversity.

Small, frequent rockfalls are thought to dominate the erosion of mountains above rockfalls, and little is known about rare large landslides as material is rapidly reworked. Here, the authors present sub-surface data from a large rock avalanche showing how such landslides can be recognized from their deposits.

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.

A wide range of policies and actions can be used to address energy insecurity, and there are many actors and institutions to carry them out. This Perspective provides an overview of the many levers, or opportunities, that electricity sector actors have to reduce energy insecurity and affordability in the United States.

Environmental heterogeneity in three-spined stickleback pairs contributes to deviations from parallel evolution, but genomic targets of selection were more parallel between environmentally similar pairs, suggestive of a continuum of parallel evolution.

Stuart Cook and colleagues study the role of TTN (titin)-truncating variants using a combination of heart physiology experiments in rats and genomic analysis in humans. Their data show that TTN variants are associated with a range of cardiac phenotypes in healthy individuals and in patients with dilated cardiomyopathy.

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).

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.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

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.

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.

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.

IL-11 is identified as a key regulator of ERK–AMPK–mTORC1 signalling, metabolism, inflammation and age-related disease and lifespan in mouse and human.

Cell-free RNA (cfRNA) is a promising analyte for cancer diagnosis. Here, the authors determine the baseline cell-free transcriptome in the absence of cancer and identify tissue- and subtype-specific cfRNA biomarkers in breast and lung cancer patients.

Here the authors compare the efficacy between sacubitril/valsartan and valsartan in improving diffuse myocardial fibrosis in patients with hypertensive heart disease, assessed as change in interstitial volume with cardiovascular magnetic resonance. The results show potential myocardial benefits of sacubitril/valsartan beyond blood pressure control.

IL11 contributes to the development of non-alcoholic steatohepatitis (NASH) through incompletely understood mechanisms. Here, the authors report that lipotoxicity-driven autocrine IL11 activity underlies hepatocyte metabolic dysfunction and death via a NOX4/ERK-mediated mechanism while paracrine IL11 activity stimulates hepatic stellate cells contributing to fibrosis and inflammation in the context of NASH.

Repair processes in kidney are impaired in severe disease. Here, the authors show that in kidney failure, genetic or pharmacologic inhibition of IL11 releases the brake on regeneration, reverses tissue damage and restores kidney function.

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.

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.

The extent to which COVID-19 vaccination protects against long COVID is not well understood. Here, the authors use electronic health record data from the United States and find that, for people who received their vaccination prior to infection, vaccination was associated with lower incidence of long COVID.

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.

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.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

An analysis of tree survival data from forest sites worldwide shows that in the tropics, rare tree species experience stronger stabilizing density dependence than common species, wheras no correlation of stabilizing density dependence and abundance exists in the temperate zone.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

In interstitial lung disease, aberrant KRT8+ basaloid cells impair alveolar repair mechanisms. Here they show that Interleukin-11 expression in KRT8+ cells potentiates their pathological properties and causes lung scarring, which can be prevented by anti-IL11 therapy.

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.

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.

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

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.

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.

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 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.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

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.

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.

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.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.