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NextBrain is an open source, probabilistic atlas of the entire human brain, assembled using artificial-intelligence-enabled registration and segmentation methods to reconstruct the multimodal serial histology of five human half brains, and which can be used to automatically segment brain MRI scans into 333 regions.

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.

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.

JWST data show that the exoplanet WASP-18b has thermally distinct regions of its dayside. The authors mapped the sizes of these regions, measured their temperatures and potentially identify water destruction in the hottest region.

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.

Tsusaka et al. discover that histone deacetylases, which are well known to remove protein modifications, such as lysine acetylation and β-hydroxybutyrylation, can also reverse their chemical activity to add lysine modifications.

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

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.

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.

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.

The authors identified a protective genetic allele associated with lower PU.1 (SPI1) expression in myeloid cells by conducting a genome-wide scan of Alzheimer's disease (AD). PU.1 binds the promoters of AD-associated genes (e.g., CD33, MS4A4A & MS4A6A, TYROBP) and modulates their expression, suggesting it may reduce AD risk by regulating myeloid cell gene expression.

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.

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.

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.

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.

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.

 An analysis of rare coding variants across 22 common traits and diseases indicates that these variants will contribute substantially to biological insights but modestly to population risk stratification.

Transcriptomic analysis of astrocytes in the acute, subacute, and chronic phases after traumatic brain injury reveal an evolving dynamic shift from neuroinflammation to neurodegeneration, and to a limited extent, regeneration.

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.

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.

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.

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.

Histone acetylation is a ubiquitous hallmark of transcription. Here the authors provide evidence that the majority of histone acetylation is dependent on transcription, specifically due to the requirement of RNAPII for the recruitment and activity of histone acetyltransferases.

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.

The identity of stem-cell memory progenitor cells has been unclear. Lugli and colleagues use high-dimensional approaches to identify two new progenitor populations of human T cells—one giving rise to a functional lineage, the other to an exhausted-like one.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

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.

γδ T cells are generally considered innate‐like lymphocytes. Here the authors sequence human γδ T cell receptors (TCR) to show focusing of the private Vδ1 TCR repertoire, suggesting that, unlike Vδ2 T cells, the Vδ1 T cell compartment has adaptive attributes.

Benjamin Ravenhill et al. use a mass spectrometry approach to enrich and quantify the proteome of the surface of red blood cells (RBCs) from donors in Senegal and the United Kingdom. They find 240 high confidence RBC cell surface proteins and identify differences between the populations as well as potential receptors for Plasmodium.

Computational methods have made progress in improving classification accuracy and throughput of pathology workflows, but lack of interpretability remains a barrier to clinical integration. Here, the authors present an approach for predicting clinically-relevant molecular phenotypes from whole-slide histopathology images using human-interpretable image features.

Current methods for detection of tuberculosis rely mostly on bacterial culture from sputum. Here, the authors provide preclinical evidence that a positron-emitting mimic of the disaccharide trehalose ([¹⁸F]FDT) can be used as a radiotracer for the imaging of tuberculosis-associated lesions and monitoring the effects of treatment.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

The phase separation of two species of associating polymers is suppressed by a magic-number effect for certain combinations of the numbers of binding sites. Here the authors use lattice simulations and analytical calculations to show that this magic-number effect can be greatly enhanced if one component has a rigid shape.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

Linkage disequilibrium graphical models (LDGMs) derived from genome-wide genealogies provide an efficient representation of LD, yielding large improvements in runtime for LD matrix computations. LDGMs will enable methods that scale to millions of variants and individuals.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

JWST spectroscopy confirms redshifts for two very luminous galaxies with z > 11, and also demonstrates that another candidate with suggested z ≈ 16 instead has z = 4.9.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

A method for measuring oxygen abundances using optical and far-infrared emission lines provides absolute metallicities of the interstellar gas in Markarian 71 and could be applied across cosmic history.