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Analysis of 20 chemical and morphological plant traits at diverse sites across 6 continents shows that the transition from semi-arid to arid zones is associated with an unexpected 88% increase in trait diversity.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

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.

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.

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 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.

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.

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.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Mark Daly, Manuel Rivas and colleagues used next-generation sequencing to study the coding exons of 56 genes from regions previously associated with Crohn's disease. Follow-up analyses in independent case-control series confirmed association of many newly discovered rare variants with disease risk.

Small-molecule senolytic compounds targeting BCL-xL were beneficial in a mouse model of diabetic edema and well tolerated when tested in a phase 1 trial involving eight patients with diabetic macular edema.

Obtaining a comprehensive proteomic profile for complex samples is still an elusive task. Here, the authors present an LC-MS/MS workflow including micropillar arrays, wide isolation windows and AI-based data analysis to boost proteomic coverage and throughput for multiple proteomic samples.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

The presented Mean-Shift Super Resolution (MSSR) algorithm can extend spatial resolution within a single microscopy image. Its applicability extends across a wide range of experimental and instrumental configurations and it is compatible with other super-resolution microscopy approaches.

The origin, evolution and domestication of Citrus and the genealogy of the most important wild and cultivated citrus varieties.

Cluster states are a key resource in quantum technologies, but generation of large-scale 2D cluster states faces several difficulties. Here, the authors show how to generate a 2 × n ladder-like cluster state via sequential emission of time- and frequency multiplexed photonic qubits from a transmon-based device.

This study assesses the effectiveness of a second COVID-19 mRNA booster vaccine against severe disease using data from Chile. The authors find that the effectiveness of the second mRNA booster was high with a range of different background vaccination schemes, but there was evidence of waning over time.

JWST and Keck II spectral observations of Saturn’s moon Titan reveal methyl (CH₃) as well as non-local thermodynamic equilibrium emission bands of CO and CO₂. Imaging shows clouds in Titan’s northern hemisphere at several epochs, with some appearing to evolve in altitude.

Pdr5 is an ABC transporter conferring multidrug resistance to pathogenic fungi. Here, structural analysis of Pdr5 provides insights into the transport mechanism featuring asymmetric movements of Pdr5 domain and enabling efflux of a broad spectrum of compounds.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

Repurposed antiviral drugs present as a valuable resource in the defence during outbreaks, with rigorous evaluation in large animal models keys for translation to clinical implementation. Here, the authors explore the antiviral activity of favipiravir against Zika virus and SARS-CoV-2 in cynomolgus macaques, in order to support future clinical investigations into this RNA polymerase inhibitor.

Data on geographically restricted SARS-CoV-2 variants is lacking in some regions. In this nationwide effort including 18 public health labs, the authors used genomic epidemiology and travel data to understand the origin and spread of 2 variants of interest that predominated during the second wave of the pandemic in Nigeria.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Warming temperatures and interactions between plants are the main drivers of changes in Arctic plant communities in response to climate change, and there is no evidence of overall biotic homogenization.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

The mechanism of stress fibre assembly by the coalescence of actin filaments in the cell cortex has now been found to account for the transmission of mechanical forces throughout the entire cell along stress fibres.

This study analysed genetic data of soil-transmitted helminths from 27 countries, revealing diversity impacting molecular test accuracy and highlighting the need to adapt diagnostics for effective STH surveillance.

A base-editing approach optimized to target the retina shows high editing rates in a mouse model of Stargardt disease, as well as in nonhuman primates and ex vivo human retinal explants, paving the way for potential clinical applications.

CEBPA is frequently mutated in acute myeloid leukemia (AML), but the transcriptional impact of the AML-associated isoform remains unclear. Here, the authors show that CEBPA-mutant cells have reduced inflammatory expression and higher sensitivity to ER stress due to impaired function of AP1 factors.

Sul-2 is a steroid sulfatase in c.elegans. Here the authors show that, in the absence of sul-2 enzymatic activity, worm lifespan is increased, and that chemical inhibition ameliorates symptoms of neurodegenerative disorders in worms and mice.

Hydroxychloroquine did not confer protection against SARS-CoV-2 infection or reduce the viral load after infection in macaques; these findings do not support the use of hydroxychloroquine as an antiviral drug treatment of COVID-19 in humans.

The mechanism of action of daptomycin, a lipopeptidic antibiotic, is unclear. Here, the authors show that Ca²⁺-daptomycin simultaneously interacts with lipid-coupled precursors of the bacterial cell envelope and with the anionic phospholipid phosphatidylglycerol, forming a tripartite complex.