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An improved strategy for siting food and energy production is needed to avoid further habitat loss. This paper presents a multi-sector framework that can empower land use planners to find synergies across conservation and development sectors.

Cryo-electron microscopy structures of three large ornate natural bacterial RNA molecules reveal their quaternary structures and intra- and intermolecular interactions that stabilize them.

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.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

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 CRISPR screen reveals that loss of structural components of the SAGA complex derails hematopoiesis by decoupling epigenetic control. This halts stem cell maturation, triggers a pathogenic interferon program and boosts human MDS-L cell growth.

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.

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.

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.

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.

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.

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.

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.

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.

Elebsiran plus PEG-IFNα improved hepatitis B surface antigen (HBsAg) loss rates compared with PEG-IFNα alone in patients with chronic hepatitis B virus infection. Furthermore, prior response to the BRII-179 vaccine was associated with higher HBsAg clearance, suggesting its potential as a predictive tool for identifying patients more likely to benefit from therapies.

This study provides the structural and biochemical characterization of the RSV NS1/MED25 ACID complex, revealing how RSV exploits fuzzy interfaces between coactivators and transcription factors, including ATF3, to modulate host gene transcription.

Targeting extracellular matrix (ECM) remodelling is a feasible avenue to prevent cancer aggressiveness and metastasis. In this study, Kay et al. show that metabolic flux in cancer-associated fibroblasts is coupled to enhanced proline synthesis by PYCR1 to support elevated production of collagen-rich ECM, thus contributing to cancer spreading.

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.

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.

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.

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 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.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

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.

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).

Zaman, Yang and Huang et al. demonstrate MDK’s suppressive effect on amyloid-β and its impact on amyloid burden and microglial activation in Alzheimer disease mice, highlighting its protective role in pathogenesis.

An Fe^III/V redox mechanism in Li₄FeSbO₆ on delithiation without Fe^IV or oxygen formation with resistance to aging, high operating potential and low voltage hysteresis is demonstrated, with implications for Fe-based high-voltage applications.

EBV (Epstein-Barr virus)-targeted therapy is limited by efficient agents inducing lytic cycle in cancer cells. Here they report a transcriptional activator incorporated into lipid nanoparticles that could specifically activate endogenous BZLF1 and induce lytic reactivation in EBV-positive cancer cells thereby suppress tumor progression.

In this study, the authors use a maternal infection mouse model to show that Zika virus infection during pregnancy reshapes offspring immunity in a sex-specific manner, weakening neutrophil defenses and heightening vulnerability to infections and inflammation later in life.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Payton et al. develop small-molecule inhibitors of kinesin KIF18A able to selectively kill cancer cells with high chromosomal instability and demonstrate that the inhibitors are therapeutically beneficial in cancer patient-derived in vivo models.

Structural variations (SV) contribute to inter-individual variability. Here, the authors describe a first-generation multi-ancestry Asian SV catalogue containing 73,035 SVs from 8392 Singaporeans to provide insights into Asian SV diversity.

The phase-out of coal will require targeted strategies. New research assesses the retirement vulnerability of coal plants in the USA based on similarity to plants with announced retirements. The findings highlight strategies to guide and accelerate phase-out.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Here the authors identify 33 individuals with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in the gene encoding Densin-180, a scaffold protein present at postsynaptic sites in neurons of the central nervous system.

Dnmt3a mutations in mouse haematopoietic stem and progenitor cells equivalent to R882 mutations in human cause increased mitochondrial respiration, suggesting that this is a mechanism of clonal haematopoiesis and a potential therapeutic target.

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

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.

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.