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T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

Drugs of abuse are known to induce changes in synaptic strength in the reward neurons of the brain. Two recent studies shed some light on how drug-induced plasticity might mediate addictive behavior long after drug use.

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.

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.

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.

An international team of researchers finds high potential for improving climate projections by a more comprehensive treatment of largely ignored Arctic vegetation types, underscoring the importance of Arctic energy exchange measuring stations.

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.

Single-cell analysis reveals how anti-hypertensive drugs affect the risk of severe disease in patients with COVID-19 who have hypertension.

Pancreatic tumors are frequently divided into basal and classical subtypes. Here, the authors use single cell sequencing to investigate organoids derived from pancreatic cancer tissue and find a hierarchy of distinct cell states, and classical and basal cells existing within the same tumor.

The high degree of subtype plasticity in small cell lung cancer (SCLC) poses a therapeutic challenge. Here, the authors show that the non-neuroendocrine (non-NE) subtype of SCLC is sensitive to ferroptosis while the neuroendocrine (NE) subtype is vulnerable to TRX anti-oxidant pathway inhibition, and the combination of these two treatments in SCLC circumvents non-NE/NE subtype plasticity.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

Single-cell analysis of COVID-19 patient samples identifies activated immune pathways that correlate with severe disease.

A latent diffusion model pre-trained on pairs of natural images and text descriptors can be adapted to generate diverse and visually plausible synthetic chest X-ray images whose appearance can be controlled with free-form medical text prompts.

Genetic factors have been found to be associated with severe COVID-19. Here, the authors integrated genomic, proteomic, and single-cell data to identify ELF5 as a candidate risk gene with a possible role in respiratory epithelial cells, which are targeted by SARS-CoV-2.

Salivary gland cancers (SGC) respond poorly to immunotherapies and new treatment strategies are needed. Here, the authors develop an integrated analysis of advanced SGC to characterize the immune microenvironment and identify potential therapeutic vulnerabilities.

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.

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.

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.

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.

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.

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.

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.

Neural coding of goal direction remains unclear in insects. Here, the authors describe goal-direction neurons in the monarch butterfly brain that specifically encode the insect’s desired flight direction during spatial orientation.

Thanks to their strong light-matter interaction, atomically thin transition metal dichalcogenides are ideal active materials for cavity quantum electrodynamics. Here, the authors embed a WSe₂monolayer within a Tamm-plasmon-polariton cavity, and observe exciton-polariton formation at room temperature.

Atomically thin transition metal dichalcogenides constitute an ideal platform to investigate solid state excitonic effects. Here, the authors provide experimental evidence of a localized biexciton in a monolayer of WSe₂, which induces an emission cascade of single photons.

Optoelectronic devices such as conventional semiconductor lasers are used to study the chaotic behaviour of nonlinear systems. Here chaos is observed for quantum-dot microlasers operating close to the quantum limit with potential for new directions in the study of chaos in quantum systems.

Future quantum communication technologies require entanglement between stationary and flying qubits, in systems that are inherently scalable. To this end, De Greveet al.present full state tomography of a qubit pair formed by entangling a quantum dot spin and a photon, with a fidelity of over 90%.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The length of single-particle tracking experiments are limited due to photobleaching. Here the authors achieve long-term single-particle tracking with continuous fluorophore exchange in DNA-PAINT and use this to observe DNA origami on lipid bilayers for tens of minutes.

Atomically thin transition metal dichalcogenides are an ideal platform to investigate the underlying physics of strongly bound excitons in low dimensions. Here, the authors demonstrate the formation of a bosonic condensate driven by excitons in two-dimensional MoSe₂ strongly coupled to light in a solid-state resonator.

The wealth of data generated by single-cell RNA sequencing can be used to identify gene sets across cells, as well as to identify specific cells. Lukassen and colleagues propose a method combining matrix factorization and variational auto encoders that can capture both cross-cell and cell-specific information.

Pulse-excited resonance-fluorescence single-photons are generated on demand from a single quantum dot embedded in a microcavity under s-shell excitation with an ultrafast laser source.

Boson sampling with three, four and five photons with high efficiency, purity and indistinguishability is realized using a quantum dot–micropillar as the single-photon source. A record-breaking sampling rate of 4.96 kHz is achieved.

Radke et al. found an interferon response in the brainstem nuclei of acute COVID-19 that, in addition to the inflammatory reaction, spreads throughout the vascular unit altering glial cells and resolves in late disease states in the absence of brain infection.

Light and matter excitations from host media can hybridize in the strong coupling regime, resulting in the formation of hybrid polariton modes. Here, the authors demonstrate hybridization between tightly bound excitons in a MoSe₂ monolayer and excitons in GaAs quantum wells via coupling to a cavity resonance.

Necroptosis, a form of cell death, occurs in acute renal injury. Here, the authors show that ferroptosis—a form of cell death dependent on iron - also occurs during acute kidney injury, and show that an inhibitor of ferroptosis can improve survival in a mouse model of acute kidney damage.