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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.

A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

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.

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.

Single-cycle and sub-cycle field transients are typically generated by external pulse compression where a combination of nonlinear broadening followed up by dispersion compensation is used. Here, Balciunas et al. use self-compression in a Kagome fibre to generate phase-controlled single-cycle pulses.

Magnetotail reconnection plays a crucial role in explosive energy conversion in geospace. Here, the authors show that magnetotail reconnection starts from electron reconnection in the presence of a strong external driver, which then develops into ion reconnection.

By integrating DNA genotype and RNA sequencing data from human samples, d’Escamard et al. identify a gene regulatory co-expression supernetwork that plays an important role in fibromuscular dysplasia, a poorly understood disease affecting 3–5% of adult females.

Mitchell et al. identify reduced osteoprogenitors and increased mesenchymal stromal cells in old bone marrow niche, which creates an IL1-mediated inflammatory milieu that skews myeloid differentiation and impairs haematopoietic regeneration.

Influenza virus infection causes injury to the lung. Here, Pervizaj-Oruqaj et al. show that Plet1 expressed by lung macrophages promotes epithelial repair by boosting epithelial cell proliferation and barrier function.

This study uncovers a critical link between DNMT3A-driven CHIP and heart failure and, in particular, it shows that DNMT3A inactivation in monocytes boosts the release of HB-EGF, which activates fibroblasts inducing diffuse fibrosis in the heart.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Seegren et al. demonstrate that the mitochondrial calcium uptake complex is a key molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation.

The molecular basis of the metastatic disease in prostate cancer remains poorly characterised. Here, the authors investigate the interaction of tumor suppressor and epigenetic factor genes and highlight the role of Kmt2c deficiency in facilitating lung metastasis.

The genetics of uveal melanoma has mainly been studied in primary tumours. In this study, the authors perform whole genome sequencing as well as immune cell profiling of biopsy samples obtained from metastatic uveal melanoma patients, providing an updated genomic landscape of these advanced lesions.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

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 significant part of the subpolar North Atlantic has warmed less over the past century than the rest of the global ocean, a feature called the North Atlantic warming hole. Here, the authors show that this anomaly can be explained by remote atmospheric forcing from the rapidly warming Indian Ocean.

Genomic analysis of neuroblastoma has revealed important disease etiology. In this study, the authors assembled whole genome, exome and transcriptome data from over 700 neuroblastomas and identified molecular signatures correlated with age, and rare, potentially targetable variants overlooked in smaller cohorts.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Identification of cancer driver genes, especially those that can act as tumour suppressors or oncogenes depending on context, remains a challenge. Here, the authors introduce Moonlight, a tool that integrates multi-omic data to address this challenge and identify numerous dual-role cancer genes.

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.

Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

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.

Neuroendocrine prostate cancer (NEPC) is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, resulting in resistance to AR-targeted therapy. Here they report ONECUT2 to drive NEPC tumorigenesis via regulation of hypoxia signaling and tumor hypoxia, and find hypoxia directed therapy to be effective in NEPC.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

The mechanisms that determine whether fibrosis occurs during chronic skin inflammation are poorly understood. Here, the authors show that chronic inflammatory skin diseases characterized by skin fibrosis share activation of EGFR-STAT1 signaling in pathologic fibroblasts as a disease defining signaling mechanism.

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.

Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.

A genomic and transcriptomic analysis of 2,754 childhood acute lymphoblastic leukemias identifies 376 putative driver genes, and associations between disease subtypes and prognosis.

The neural dynamics that optimize coordination of sensorimotor behaviour are not fully understood. Here authors show that the cerebellum receives a copy of the motor commands from the cerebrum during movement preparation, likely to generate motor predictions. During the execution, the cerebellum sends feedback to correct the motor cortical activity.

Recurrent histone mutations are linked to paediatric glioblastoma multiforme, an aggressive type of brain tumour.

Traditional methods for tuning the dimensions of organic electronic device structures often rely on cumbersome processes with limited resolution. Here, the authors report ultraviolet irradiation in ambient conditions for tuning structural parameters for organic small molecule hole transport layers.

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 future of marine ecosystem function under global change may be predicted by examining past trends. Here, the authors examine mass marine mortality data from 389 benthic Mediterranean species (1986–2020), highlighting heightened vulnerability within specific trait categories.

This study explores the genomic and transcriptomic landscapes of triple-negative breast cancer in African American women. The authors show that the mutational profile is broadly similar to that observed in European and East Asian ancestry women while highlighting some interesting differences.

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.

Childhood radioactive iodine exposure from the Chornobyl accident led to an increased papillary thyroid carcinoma (PTC) risk and potentially higher invasiveness depending on tumour genetic profiles. Here, the authors use genomics to characterise and predict cervical lymph node metastases in PTC patients affected by the Chornobyl accident.

This paper compares the frequency and genetic basis of clonal hematopoiesis in 136,401 admixed American participants from the Mexico City Prospective Cohort with 416,118 largely European ancestry individuals from the UK Biobank cohort.

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.

Analysis of crop yields, farmer income and bird species abundances identifies multiple positive outcomes of a large-scale Indian government-incentivized agroecology initiative.

Hydro-equivalent scaling of recent direct-drive inertial confinement fusion implosions shows that a burning plasma can be achieved with a higher laser energy.

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.

Excised signal circles are circular DNA by-products of V(D)J recombination that form a complex with the V(D)J recombinase, and when increased in abundance, result in increased mutagenesis, causing adverse outcomes in cancer.

Different clones of a mammary tumour cell line possess differential abilities to contribute to the formation of metastasis; the expression of Serpine2 and Slp1 proteins drives vascular mimicry and metastasis to the lung, with similar associations observed in human data sets, and these proteins also function as anticoagulants, thus further promoting extravasation of tumour cells.

Biomolecular phase separation arises from collective molecular interactions and is emerging as a key theme for biological function. Here the authors propose a broadly applicable method to quantify these interactions based on compositional and energetic parameters.

The interplay between driver mutations and aneuploidy during tumorigenesis is largely unexplored. Here, the authors show two types of associations, leading to different therapeutic vulnerabilities and prognoses.