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Formate produced by synthetic methylotrophic E. coli can lead to carbon loss and negatively impact bioproduction efficiency. Here, the authors report the production of formate as a widespread property of NAD-dependent methanol dehydrogenases and identify Mdhs without this overoxidation activity.

From proteomics to networks, this protocol covers the processing, analysis and interpretation of AP-MS data. Sample data are pre-processed and scored using a variety of methods, and they are then imported into Cytoscape for network analysis and visualization.

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.

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.

Stroke affects the brain in complex, highly individual ways. Here, the authors show that applying generative and causal AI methods to routinely collected brain scans may enable more closely personalized treatment recommendations.

Neural crest cells are highly multipotent stem cells, but it remains unclear how their fate restriction to specific fates occurs. Here, the authors show in zebrafish that broad multipotency is retained even after migration, suggesting that fate restriction occurs directly, but dynamically.

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.

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.

Coherent quantum transition spectroscopy of the spin of a single antiproton is reported, demonstrating Rabi oscillations of the spin and enabling improved measurement of matter/antimatter symmetry using proton and antiproton magnetic moments.

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.

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.

The authors report findings from the MOBILIZE trial, which found that exercise therapy and self-management support improved patient-reported quality of life in individuals with multiple chronic conditions.

The arcuate fascicle connection with the middle temporal gyrus has been considered unique to humans. Using high-resolution diffusion MRI, the authors systematically show this connection in chimpanzees, suggesting a gradual evolution of the language network.

The successful transport of a trapped proton cloud from the antimatter factory of CERN using a transportable, superconducting, autonomous and open Penning-trap system that can distribute antiprotons into other experiments is reported.

Results of the phase 2 trial of CD19 CAR T cell therapy lisocabtagene maraleucel in patients with relapsed or refractory follicular lymphoma, most of whom were treated in a third-line or later setting, show encouraging objective response rates in these high-risk patients.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

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 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.

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.

The presence of conformational substates of a catalytically competent 'closed' state in the ligand-free form of adenylate kinase is detected. Molecular dynamics simulations indicated that the partially closed conformations were sampled in nanoseconds, and NMR and single-molecule FRET experiments revealed the sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale.

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.

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.

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.

Quantum wires offer a platform for controlling spin–orbit coupling and therefore creating exotic phases of matter. Here, the authors use high-resolution spin- and angle-resolved photoemission measurements to identify an interaction-induced spin- and orbital-entangled state in atomic lead wires.

Individual graphene nanoribbons synthesized by an on-surface approach can be contacted with carbon nanotubes—with diameters as small as 1 nm—and used to make multigate devices that exhibit quantum transport effects such as Coulomb blockade and single-electron tunnelling.

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.

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.

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.

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.

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.

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.

Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

Bone marrow-derived cells can rapidly enter the systemic circulation, but how this is achieved is unclear. Grüneboom et al. identify tiny capillaries, termed trans-cortical vessels (TCVs), that connect the bone marrow cavity to the systemic vasculature, and show that the majority of blood in long bones passes through TCVs.

Selenium and copper are two essential trace elements whose homeostasis and distribution is regulated by hepatic release of selenoprotein P (SELENOP) and ceruloplasmin, respectively. Here, the authors show that excessive copper results in hepatic SELENOP accumulation in the trans Golgi which might limit the selenium transport to peripheral organs.

This directory was made possible by a unique international collaboration between the 633 scientists whose names appear below. It represents both the first published description of the complete sequence of most chromsomes from Saccharomyces cerevisiae, and the first published overview of the entire sequence. As such, the authors would like future papers referring to the entire sequence and/or its contents to cite this directory; future papers referring to the sequence of individual chromosomes should refer to the papers listed at the head of page 9. The authors’ affiliations appear in the papers describing the individual chromosomes.

Although genetically bland, the posterior fossa group A subgroup of ependymomas, found often in infants and associated with poor prognosis, exhibit widespread epigenetic alterations, namely a CpG island methylator phenotype; these tumours are shown to be susceptible both in vitro and in vivo to various compounds that target epigenetic modifications, such as DNA methylation and H3K27 tri-methylation.

Stehlik and colleagues show that NLRP11 is an essential component of the NLRP3 inflammasome in human macrophages.

The integration of DNA methylation profiling and targeted sequencing with neuropathology improves the diagnostic accuracy of central nervous system tumors in a population-based cohort of more than 1,200 newly diagnosed pediatric patients.

A zirconium-based crystal (baddeleyite) found embedded in a sample brought to Earth by Apollo 17 provides evidence of large-scale impact bombardment of the Moon about 4.33 Gyr ago, when the baddeleyite grain was formed. This result points to the importance of impacts in the early evolution of planetary crusts.

Herold et al. present an integrated meta-omics framework to investigate how mixed microbial communities, such as oleaginous bacterial populations in biological wastewater treatment plants, respond with distinct adaptation strategies to disturbances. They show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity.

Live-cell recordings have been an important tool for studying circadian rhythms. Here the authors use CRISPR gene editing mediated knock-in to fluorescently tag Per2 and Cry1, and study cellular circadian dynamics of these two clock proteins.

A deep residual learning framework identifies microsatellite instability in histology slides from patients with cancer and can be used to guide immunotherapy.

Focusing on two ill-characterized subtypes of medulloblastoma (group 3 and group 4), this study identifies prevalent genomic structural variants that are restricted to these two subtypes and independently bring together coding regions of GFI1 family proto-oncogenes with active enhancer elements, leading to their mutually exclusive oncogenic activation.

Affinity tagging, mass spectroscopy and a tailor-made scoring system are used to identify 497 high-confidence interactions between human proteins and human immunodeficiency virus proteins.