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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.

Here, the authors analyze the blood transcriptome of Kenyan children with severe malarial anemia and observe impaired immune responses and molecular activation of hypoxia and reactive oxygen species networks, providing insight into disease pathogenesis.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

In topological insulators, studies have largely concentrated on the spin part of the wavefunction. But the spin–orbit coupling is strong, so the orbital components of the wavefunction need to be measured as well. Surprisingly, the orbital wavefunction turns out to be asymmetric about the Dirac point.

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

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.

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.

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 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.

Castleman disease encompasses a group of disorders characterised by abnormal lymph node morphology. Here the authors use single cell and spatial transcriptomics to assess the stromal, immune and interaction architecture of different subtypes of Castleman disease, indicating potential ligand-receptor interactions between immune cells.

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.

This multiomic study, including single-nucleus DNA methylation and chromatin conformation matched with single-nuclei RNA sequencing, provides insights into the epigenomic landscape of human subcutaneous adipose tissue.

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.

Polarization observations of the fast radio burst FRB 180301 with the FAST radio telescope show diverse polarization angle swings, consistent with a magnetospheric origin of the emission.

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.

The sensitivity of mesothelioma to the treatment of immune checkpoint blockade remains elusive. Here this group reports a double blind, placebo-controlled, randomized phase III trial of PD1 inhibitor (Nivolumab) on 332 patients with relapsed mesothelioma, and to uncover determinants of efficacy.

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.

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.

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.

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.

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.

Here, English et al. show that after expanding in lymphoid tissues, CD4⁺ and CD8⁺ T cells recognising hepatic antigens migrate into specialised vascular liver areas where CD4⁺ T cells locally license hepatic dendritic cells and further expand CD8⁺ T cell numbers.

Harnessing single-nucleus RNA sequencing and spatial profiling, this work dissects unanticipated aspects of human liver regeneration to uncover a novel migratory hepatocyte subpopulation mediating wound closure following acute liver injury.

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.

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.

RAPID (rapid autofocusing via pupil-split image phase detection) is a sample-agnostic real-time autofocus method for widefield microscopy. RAPID removes most image degradation in large, cleared samples for enhanced quantitative analyses.

Obtaining a high-resolution contact map using current 3D genomics technologies can be challenging with small input cell numbers. Here, the authors develop ChromaFold, a deep learning model that predicts cell-type-specific 3D contact maps from single-cell chromatin accessibility data alone.

Transporting charged particles in a guided manner, similar to how optical fibers carry light signals, has the potential to profoundly impact the scientific and technological landscape. Here, the authors propose a viable method to realize these waveguides by leveraging Lagrange points created by the electrostatic potential around a carefully designed twisted wire in a vacuum.

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.

Nuclear morphology plays a critical role in regulating gene expression and cell function. Here, Wang et al. report that topography-induced nuclear deformation enhances the secretome of hMSCs, promoting extracellular matrix (ECM) organization and facilitating bone regeneration through matricrine effects.

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.

While HER2-targeted therapies such as trastuzumab can be effective in patients with breast cancer, resistance often develops. Here, the authors demonstrate that the histone reader ZYMND8 promotes glycerophospholipid metabolic reprogramming via c-Myc and cPLA2α to increase secretion of IL-27, mediating resistance to HER2-targeted antibodies in preclinical models of breast cancer.

Alonso and colleagues develop immune-stimulating antibody conjugates capable of specific delivery of TLR7/8 agonists to tumors, which induces durable antitumor immunity.

The magnitudes of replenishment and priming, two important but opposing fluxes in soil organic carbon (SOC) dynamics, have not been compared. Here the authors show that the magnitude of replenishment is greater than that of priming, resulting in a net SOC accumulation after additional carbon input to soils.

Machine learning can be used to identify subtypes of psychiatric disease. Here the authors identified two neurostructural subgroups in schizophrenia, each showing reproducibility and generalizability across different collection locations and illness stages, using the SuStain algorithm.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Intersectional adeno-associated viruses are important for neuroscience research but can be limited by complex and bulky design parameters. Hughes et al. present a unique and space-saving approach that simplifies toolkit development and provides expanded functionality.

Dendritic cells initiate and regulate adaptive immunity and differ according to gut anatomical location. Here the authors show that DC residing in the upper and lower intestines show differential PD-L1 and XCR1 expression and drive specific T cell responses to prevent gut inflammation.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

The core circadian transcription factor BMAL1 regulates circadian-dependent myocardial injury.

The study of lattice vibrations coupled to electronic excitations may provide an avenue for exploring exotic physical phenomena. Here, Xuet al. observe a Fano resonance in the Weyl semimetal TaAs, revealing evidence for a strong coupling between phonons and Weyl fermions.

Walking requires continual integrated information about the dynamic internal and external environment. This study reveals a pathway whereby the somatosensory cortex directly influences motor behavior based on integrated spatiotemporal information.