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A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

The majority of human genes can produce multiple isoforms, but studying their functional relevance requires tools to target specific isoforms. Here, the authors develop a CRISPR-based exon-exon junction-targeting strategy to achieve isoform-specific RNA knockdown.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

A study of millions of couples shows spouses often share psychiatric disorders. This pattern is consistent across cultures (Taiwan and Nordic countries) and has persisted for generations, impacting how these disorders are inherited.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

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.

Analysis of samples from the asteroid Ryugu provide evidence of late fluid flow in a carbonaceous asteroid, indicating that such bodies may have retained two to three times more water than previously thought.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

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.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

In a large multinational cohort study, maternal, gestational or pregestational diabetes was associated with only a small-to-moderate risk of ADHD in offspring, contrary to previous estimates that showed stronger effect sizes, attributing the differences in findings to confounding by shared genetic and familial factors.

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 authors report a computational framework for determining the meiotic/mitotic origin of nondisjunction (NDJ) in trisomies without parental data. Applying this to Down syndrome, they uncover links between NDJ error stage and leukemia genomics.

Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.

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.

Li et al. introduced tract-geometry coupling (TGC) to quantify the coupling between white matter tracts and cortical geometry in the human brain, shedding light on how the brain’s wiring and shape evolve together and its support for behavior and growth.

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.

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.

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.

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

2D semiconductors are attracting attention as a potential alternative for post-silicon electronics, but the fabrication of high-performance 2D p-type transistors remains a challenge. Here, the authors report the realization of bilayer WSe₂ p-type transistor arrays with on-state currents up to 421 μA/μm, on/off ratios exceeding 10⁷ and subthreshold swings as low as 75 mV/decade.

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.

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.

Researchers demonstrated integrated non-magnetic isolators with 24.5-dB contrast, –2.16-dB insertion loss and 2-THz (16-nm) optical bandwidth.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

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.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

The sexually transmitted human parasite Trichomonas vaginalis belongs to a clade of host-switching trichomonads that parasitize mammals, birds, livestock, and pets. Here the authors describe a chromosome-scale genome for T. vaginalis and assemblies of other bird and mammal-infecting species, identifying gene functions implicated in the spillover of trichomonads from birds to humans.

Harmonic measurements have been used extensively in ferromagnetic/heavy metal heterostructures to characterize the magnetization dynamic; however, it has remained unclear about whether such techniques could be applied to antiferromagnetic devices. Here, Cheng et al demonstrate such a harmonic measurement approach in an antiferromagnet.

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 meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Finding optimal multi-drug combinations for pancreatic cancer remains a complex task. Here, authors across three different groups apply machine learning approaches to predict synergy across 1.6 million combinations of drugs for pancreatic cancer, 307 of which are validated experimentally.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

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.

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.

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.

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.