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Population-based studies from Sweden with replication in Norway identify associations between host genetic variants and gut microbial composition and implicate short-chain fatty acid chemosensors as modulators of gut microbial richness.

Genome-wide analyses in the Norwegian HUNT study with replication in Swedish and Finnish cohorts identify host genetic variants associated with gut microbiome features and provide evidence of a causal effect of body mass index on gut microbiota composition.

The clinical outcomes and treatment responses of acute myeloid leukemia (AML) patients are heterogeneous. Here, the authors use bulk and single-cell sequencing approaches and identify two transcriptomic subtypes within NPM1-mutated AML with distinct immune evasion properties and responses to hematopoietic stem cell transplantation.

Sandén et al. report that the ligand signaling lymphocyte activation molecule family member 6 protects acute myeloid leukemia cancer cells from T cell-mediated killing, leading to immune escape, and show that this can be targeted by a blocking antibody.

Core ionization of ions in solution leads to decay processes involving interaction with the environment. Here, the authors report a non-local X-ray emission process in core-ionized Na⁺ and Mg²⁺ that can be used to probe the ions’ solvation shells.

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.

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.

Montoliu-Gaya, Salvadó et al. develop a blood-based model using tau biomarkers measured in a single analysis enabling biological staging of Alzheimer’s disease to support the diagnosis, prognosis and identification of patients likely to benefit from targeted therapies.

How hematopoietic stem cells respond, if at all, to acute anemia has remained unclear. Here, the authors show that acute anemia triggers hematopoietic stem cell proliferation and guides differentiation towards erythroid cells in a process mediated by apolipoprotein E.

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.

The fusion of two genes during the pathogenesis of cancer can create oncogenes. In this study, the authors screen pediatric B-cell precursor acute lymphoblastic leukaemia samples for the presence of fusion genes and describe fusion genes that define new molecular subtypes of the disease

Heart failure is a major health issue worldwide. Here, Egerstedt et al. perform proteomic profiling of human plasma at different stages of heart failure, providing a comprehensive analysis of changes in the plasma proteome during disease progression.

Andersson et al. identify that high Aβ₄₂/Aβ₄₀ ratios in brain protofibrils best predict lower Aβ₄₂/Aβ₄₀ ratios in the cerebrospinal fluid (CSF) and higher neurofilament light/total tau levels, indicating that CSF changes in Alzheimer’s disease reflect soluble protofibrils more accurately than amyloid plaques.

Achieving the Paris Agreement’s climate goals depends on safeguarding and monitoring the permanence of forest carbon stocks, as delays in addressing their vulnerability to disturbances drastically increase mitigation costs and efforts.

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.

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.

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.

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.

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.

TRPV2 is activated by temperature and cannabinoids. Here, the authors have used cryo-EM and electrophysiology to identify a cannabinoid binding site distinct from that of cannabidiol as a possible drug target for treatment of inflammation and immune-mediated diseases.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Clonal evolution and heterogeneity has strong implications for treatment response in acute myeloid leukemia. Here, the authors use patient derived in vivo modelling to highlight the complex clonal and evolutionary dynamics underpinning acute myeloid leukemia progression.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Follistatin promotes in type 2 diabetes (T2D) pathogenesis in model animals and is elevated in patients with T2D. Here the authors report that plasma follistatin associates with increased risk of incident T2D in two longitudinal cohorts, and show that follistatin regulates insulin-induced suppression lipolysis in cultured human adipocytes.

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

Folkersen et al. report the first results from the SCALLOP consortium, a collaborative framework for pQTL mapping and biomarker analysis of proteins on the Olink platform. A total of 315 primary and 136 secondary pQTLs for 85 circulating cardiovascular proteins from over 30,000 individuals were identified and replicated to yield new insights for translational studies and drug development.

Infection with Streptococcus pyogenes after childbirth can have life threatening consequences. Here, Catton et al. show that the epidemiologically associated bacterial R28 protein targets the human CEACAM1 receptor to facilitate the pathogenesis of bacterial sepsis.

Autoimmune Addison’s disease is a rare complex disease, which has not yet been characterized by non-biased genetic studies. Here, the authors perform the first GWAS for the disease, identifying nine loci including two coding variants in the gene Autoimmune Regulator (AIRE).

The application of polygenic risk scores to individual-level disease susceptibility is challenging, as risk is evaluated at a group-level. Here, the authors describe a machine learning method, Mondrian Cross-Conformal Prediction, that reports disease status conditional probability value at the individual level.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.