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An atomic single electron transistor, which utilizes a single atomic defect in a van der Waals material as an ultrasensitive, high-resolution potential sensor, is used to image the electrostatic potential within a moiré unit cell.

Using a treatment that activates the peripheral immune system in an animal model of amyloidosis, the authors show that monocyte-derived macrophages can modify Alzheimer’s disease progression via a TREM2-independent mechanism.

In hole-doped cuprates, the origin of a recently discovered nodal gap has posed a puzzle. Drachuck et al. perform photoemission experiments combined with muon spin rotation and neutron scattering measurements in lightly doped antiferromagnetic cuprate and put strong restrictions on the origin of the nodal gap.

Combining scRNA-seq with spatial information to enable the reconstruction of spatially-resolved cell atlases is challenging for rare cell types. Here the authors present ClumpSeq, an approach for sequencing small clumps of tissue attached cells, and apply it to establish spatial atlases for all secretory cell types in the small intestine.

Mutations in TREM2 alter risk for Alzheimer’s disease, though the mechanisms underlying risk in human cells are unclear. Here, the authors use iPS-microglia and chimeric mice to highlight altered survival, phagocytosis, migration, and transcriptional programs in microglia lacking TREM2.

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.

Single-cell analyses in a reporter mouse model and human tissues identify a rare cell subset that produces erythropoietin in vivo, opening potential new avenues for research in erythropoiesis and oxygen homeostasis.

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.

Single cell dissection of plasma cell heterogeneity in myeloma patients reveals new insights into disease that may inform early diagnosis and clinical management.

DestVI models continuous cell states in spatial transcriptomics data.

Self-incompatibility evolved to avoid self-fertilization among hermaphroditic plants, yet it remains murky how this compatibility recognition evolved. This study constructs a theoretical framework incorporating promiscuous molecular recognition into the evolutionary model of incompatibility.

Lysosomes move along microtubule tracks, and Arl8b is known to stimulate their anterograde transport. Here, the authors identified RUFY3 as an Arl8b effector that interacts with dynein-dynactin to drive retrograde transport and perinuclear lysosome positioning.

Single-molecule fluorescence in situ hybridization is performed to identify several landmark genes in the liver and their level of expression in single-cell RNA sequencing is used to spatially reconstruct the zonation of all liver genes.

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.

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.

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.

Elyahu and colleagues describe the reciprocal interplay between senescent cells (SCs) and a helper T cell population that accumulates during aging. They show that selective depletion of this T cell population increases SC accumulation, accelerates frailty and limits lifespan in mice.

Chronic UV exposure has been associated with immune system suppression. Here the authors show that enhanced tumor growth and resistance to PD1 blockade in mice exposed to UV irradiation is associated with induced expression of Ly6a in CD8 + T cells and that targeting Ly6a enhances anti-tumor immune responses in models resistant to anti-PD1.

Precise measurements of the superconducting stiffness tensor can give detailed insights into the superconductor-normal phase transition. Kapon et al. introduce the Stiffnessometer approach for sensitive magnetic-field-free measurements and find two transition temperatures in LSCO rings.

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.

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.

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.

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.

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 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.

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.

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.

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 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 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.

Here the authors provide immunogenicity and efficacy data at 3-month follow-up for vaccinees who have received a fourth dose of either mRNA1273 or BNT162b2. Both vaccines were highly effective against substantial symptomatic disease, but had little effect against SARS-CoV-2 infection.

Single-cell RNA sequencing and single-molecule RNA transcript imaging have been used to characterize spatially and temporally resolved mouse liver and parasite expression programmes during infection with the rodent malaria parasite Plasmodium berghei ANKA.

Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans

At early time points after vaccination with a single dose or two doses of the BNT162b2 mRNA COVID-19 vaccine, breakthrough SARS-CoV-2 infections can be disproportionately caused by the B.1.1.7 or B.1.351 variants of concern, underlining the need to ensure rapid and complete vaccination.

Around the world, governments are urging populations to receive a third COVID-19 vaccine dose. Here, the authors compare immunogenicity, reactogenicity and effectiveness of a third dose versus the second dose of the BNT162b2 vaccine in a large group of healthcare workers in Israel.

Epithelial gene expression has been shown to be zonated along the crypt-villus axis, but mechanisms shaping this spatial variability were unknown. Here, Bahar Halpern et al. uncover zonation of mesenchymal cells, including Lgr5+ telocytes, which regulate epithelial gene expression at the villus tip.

The expression profile and tissue coordinates of liver endothelial cells are determined using a paired-cell sequencing approach that extracts spatial information from attached hepatocytes.

Organic magneto-transport is of interest due to numerous potential applications, including solar cells. Here, the authors study high-field magneto-photocurrent to analyse charge-transfer excitons in organic photovoltaic cells, showing that spin-mixing mechanisms are operational over 8 Teslas.

This single-cell RNA-sequencing protocol combines FACS-based index sorting and an analytical pipeline into a single framework. MARS-seq2.0 can handle tens of thousands of cells with a dynamic range suitable for the analysis of complex tissues.

Blocking the PD-1 pathway was shown to be effective in amyloid beta mouse models, yet little is known about its therapeutic potential in models of tauopathy. The authors show here that blocking PD-L1, a PD-1 ligand, is similarly effective, and that both treatments reversed cognitive deficiencies, and modified disease pathology not only in an animal model of AD, but also in the DM-hTAU mouse tauopathy model, through a mechanism that involves monocyte-derived macrophages.

In this study, the authors show that host microbiota play a key role in modulating microglia homeostasis. Germ-free mice or mice with only limited microbiota complexity displayed defects in microglial cell proportions and maturation, leading to impaired innate immune responses. The authors find that short-chain fatty acid signaling regulates these effects in vivo.