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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.

The cryo-EM structure of phage φTE is presented, revealing a distinct neck topology, tail sheath baseplate organization and oligomeric state of the tape measure protein. These features suggest a mechanism linking base plate conformational changes to sheath contraction and genome ejection.

The imaging of magnetic domains in three-dimensional solids has been hampered by a lack of suitable methods. The authors show that Talbot-Lau neutron tomography is capable of visualizing the domain structure of an iron silicide bulk crystal.

In cyclotron-based proton therapy facilities, beam loss due to large momentum spread can limit ultrahigh dose rates. Now, beam transmission is enhanced and higher dose rate is achieved by introducing momentum cooling through a wedge.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

Gene brushes patterned as synthetic operons on two-dimensional silicon compartments with defined geometry allow the investigation and regulation of nanoscale multi-protein assemblies.

In this Review, Paterson and colleagues describe how bioelectronic approaches involving site-specific targeting of the autonomic nervous circuit could be used to treat cardiovascular disease, and reflect on current bioelectronic modalities, their limitations and future ways to improve therapeutic efficiency.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

Observation systems are not sufficient to determine the relationship between mélange strength and calving frequency. Here the authors used the derivation of digital elevation models from radar interferometry data to study Jakobshavn Isbræ and show an inverse correlation between mélange thickness and calving rate.

The authors report resonant soft x-ray scattering and polarimetry measurements on epitaxial thin films of La3Ni2O7. They find a diagonal bicollinear double spin stripe order, with no evidence of charge modulation.

The complexity of epithelial cell states in the fibrotic niche in the context of chronic kidney disease remains incompletely understood. Here the authors integrate snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease.

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.

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.

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.

Genome-wide sequencing of 180 ancient individuals shows a continuous gradient of ancestry in Early-to-Mid-Holocene hunter-gatherers from the Baltic to the Transbaikal region and distinct contemporaneous groups in Northeast Siberia, and provides insights into the origins of modern Uralic and Yeniseian speakers.

A standardized, realistic phantom dataset consisting of ground-truth annotations for six diverse molecular species is provided as a community resource for cryo-electron-tomography algorithm benchmarking.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Type VI secretion systems (T6SSs) translocate effector proteins into eukaryotic and bacterial recipient cells and are present in many Gram-negative bacteria. Here the authors present the 3.7 Å cryoEM structure of the E.coli T6SS baseplate wedge comprising TssK–TssF–TssG and propose a model for the T6SS baseplate and needle complex.

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.

The East Antarctic ice sheet was larger than present during past cold periods. Seafloor geophysical data show that in the Ross Sea, the extended ice sheet was underlain by an active hydrologic system during the glacial termination.

Testicular germ cell tumours (TGCT) are the most common cancers in young men. Here, the authors analyse the genomic landscape of TGCT using data from the Genomics England 100,000 Genomes Project, revealing divergent evolutionary trajectories and the prevalence of human leukocyte antigen loss.

A fluidic system with spatially reconfigurable hot spots generated by optical pumping of plasmonic nanorods is demonstrated, creating virtual barriers by generating local heating via photothermal conversion, for potential applications in chemical synthesis, lab-on-chip devices and microbiology.

Omecamtiv mecarbil and Mavacamten are small molecules directly modulating the force produced by β-cardiac myosin. In this work, the authors describe how the modulators Omecamtiv mecarbil and Mavacamten can have opposite effects on cardiac myosin force production despite occupying the same pocket.

Analysing changes in observations of birds, butterflies and plants in Great Britain over more than 50 years, the authors show that climate change and land conversion have led to increases in richness, biotic homogenization and warmer-adapted communities over both the long and short terms.

Gastrointestinal motility disorders affect over 20% of the population, yet current therapies provide limited relief. Here, the authors show that in a swine model a closed-loop GI neuroprosthesis restores peristalsis and enhances metabolic responses via targeted electrical and chemical stimulation

Leucine-rich repeats (LRRs) can form horseshoe-like structures with different curvatures in nature. A computational approach now allows the design of 12 new LRR proteins with precise curvatures, using defined building blocks and junction modules.

An all-optical manipulation of the Berry phase based on stimulated Raman adiabatic passage is demonstrated in an individual nitrogen–vacancy centre in diamond. The adiabatic control is 100 times faster than that demonstrated before in atomic systems.

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

The study of biomineralization processes in molluscs can help to understand the properties of the final composites. Here, Hovden et al. have studied the early stages of nacre formation using high resolution scanning transmission electron microscopy, giving new insight into nacre formation.

The authors introduce and demonstrate experimentally an all-optical platform in fibres for reconfigurable operations at the sub-nanosecond time scale. This paves the way towards programmable hardware for photonic computing and machine learning.

HMCES protects abasic sites that block DNA replication via covalent protein attachment. Crystal structures of the Escherichia coli HMCES homolog YedK reveal that the conserved SRAP domain forms a thiazolidine linkage with the abasic site, explaining the stability of the DNA-protein cross-link and its specificity for DNA lesions at stalled replication forks.

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.

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 the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

APOBEC mutational signatures are commonly found in multiple cancer types. Here, the authors utilize multi-omics analyses to reveal that the cooccurrence of APOBEC associated mutagenesis and tobacco-smoking-related mutations affects lung tumor evolution and age at onset of lung cancer from smokers.

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.

Lineage tracing analyses of cells from two monozygotic twins presenting with myelofibrosis in adulthood provide evidence of in utero transplacental transmission of the tumorigenic clone.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

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.

Subducted slabs may experience transient weakening during mineral phase transitions, consistent with slab stagnation in the mantle transition zone, according to a synchrotron beamline study of the quartz-to-coesite and olivine-to-ringwoodite phase transitions.

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.

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.