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Sharing of whole genome sequencing (WGS) data improves study scale and power, but data from different groups are often incompatible. Here, US genome centers and NIH programs define WGS data processing standards and a flexible validation method, facilitating collaboration in human genetics research.

Glacier surges are rapid ice flow acceleration and mass transport events, which can threaten nearby communities, infrastructure and habitats. This Review discusses the global distribution, behaviour and associated hazards of glaciers that are prone to surging and how these are being affected by climate change.

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.

Children born to women living with HIV suffer increased morbidity and, in low-income settings, have two to three times the mortality of infants born to women without HIV. Here, we profile the milk metabolome of 326 women living with and without HIV sampled longitudinally for 18 months postpartum using global metabolomics. Our findings demonstrate that milk tryptophan content and availability decrease among WLWH, which may indicate perturbations in milk tryptophan catabolism.

Electrochemical carbon capture provides a sustainable method for effective carbon management. Here, the authors develop a modular porous solid electrolyte reactor system, achieving continuous carbon capture from air and flue gases through a recirculation mode with high efficiency and stability.

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).

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.

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.

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.

Using historical data combined with more recent satellite observations, these authors show that global phytoplankton biomass has been declining during the past century.

Disparities in risk and outcomes of pediatric acute lymphoblastic leukemia (ALL) are apparent between different ancestries. Here the authors identify genetic variants with African ancestry-specific risks for developing pediatric B-cell ALL that are also linked to greater 5-year mortality risk.

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.

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

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.

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.

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.

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.

In mammals, the enzyme TGDS produces UDP-4-keto-6-deoxyglucose, which binds to the catalytic pocket of UDP-xylose synthase, thereby regenerating the essential NAD⁺ cofactor of UDP-xylose synthase in conditions of low NAD⁺.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Nucleosome profiling from cell-free DNA (cfDNA) represents a potential approach for cancer detection and classification. Here, the authors develop Griffin, a computational framework for tumour subtype classification based on cfDNA nucleosome profiling that can work with ultra-low pass sequencing data.

Ancient DNA analyses reveal that Viking Age migrations from Scandinavia resulted in differential influxes of ancestry to different parts of Europe, and the increased presence of non-local ancestry within Scandinavia.

Investigations of human cardiac disease involving human pluripotent stem cell-derived cardiomyocytes are limited by the disorganized presentation of biomechanical cues resulting in cell immaturity. Here the authors develop a platform of micron-scale 2D cardiac muscle bundles to precisely deliver physiologic cues, improving reproducibility and throughput.

Machine learning and satellite images are used to identify intensive animal agricultural facilities in the United States, which are otherwise difficult to track. This can facilitate monitoring their compliance with environmental law.

A cross-ancestry GWAS meta-analysis of β-amyloid deposition in East Asian and European populations identifies a novel SORL1 locus and highlights its differential expression in microglia associated with β-amyloid positivity.

Here the authors reveal via whole genome sequencing of an East Asian AD cohort a common variant locus (APCDD1), rare noncoding variants in excitatory neurons, and short tandem repeat expansions, suggesting a cumulative effects model for Alzheimer’s risk.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.