Search

A global synthesis of >600 studies finds that across agro-ecosystems, grasslands and forests in temperate and tropical zones, increasing plant diversity has a consistently positive effect on plant performance and the suppression of antagonists.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Dissolved oxygen levels in the Proterozoic surface ocean decreased from the Equator towards the mid–high latitudes, the opposite of the modern latitudinal gradient, according to a compilation of I/Ca proxy records and Earth system modelling.

FUGAsseM predicts protein function in microbiomes using coexpression patterns from metatranscriptomes and diverse community-wide data.

Proteomic analysis of paired cerebrospinal fluid and plasma samples from 2,171 individuals drawn from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium, reveals age-related changes in the ratios of proteins in the cerebrospinal fluid and plasma that are associated with cognitive function, enhancing understanding of blood–brain barrier dynamics in aging.

Iacobucci et al. present the single-cell transcriptomic profile of patients with B cell acute lymphoblastic leukemia, report enriched multipotency and develop a multipotency score that is associated with worse survival in pediatric patients.

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.

How reduced blood flow plays a role in progressive white matter loss during aging and associated cognitive decline is unclear. Here the authors show that selective constriction and rarefaction of capillary–venous networks contribute to age-related hypoperfusion and white matter damage in mice.

Large-scale analyses of bird species traits reveal that land-use change reduces resilience of key ecological functions more than previously thought.

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 complexity of epithelial cell states in the fibrotic niche in the context of chronic kidney disease remains incompletely understood. Here the authors integrate snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease.

Spatial cell distribution within a tissue microenvironment is a rapidly advancing field. Here, authors assess three commercially available single-cell resolution spatial transcriptomics approaches (CosMx, MERFISH, and Xenium) to inform which technology outperforms for immune profiling of solid tumors using patient samples.

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.

A statistical framework quantifies single-cell batch variation and recovers meaningful biological signals.

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.

Chromatin topology can impact gene regulation. Here, Wu et al. show that evolutionary changes in chromatin structure, particularly CTCF loops, can drive distinct transcriptional landscapes and isoform diversity contributing to human-specific traits.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The mechanisms that control the presynaptic abundance of GABAB receptors (GBRs) remains unclear. This study shows that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs, and that selective loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

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.

Shi et al. present a hybrid dependency map based on machine-learning analysis of gene essentiality data from the DEPMAP database, translated to data from TCGA. This application can be used to visualize other gene essentiality data.

Immunotherapy has yet to demonstrate efficacy for patients with glioblastoma. Here, the authors employ human single-cell RNA-seq, spatial transcriptomics, and a preclinical mouse model to show that glioblastoma cell-derived synaptogenic factor Thrombospondin-1 promotes neuronal circuit remodeling and regional immunosuppression, highlighting a potential therapeutic target.

Evaluating the immune status of newborns helps recognition of those who are at higher risk for serious infectious diseases. Here authors identify lower, epigenetically inferred,

neutrophil-to-lymphocyte ratios during the first week of life as risk factor for sepsis and provide insight into the underpinning epigenetic and transcriptional patterns.

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.

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 novel gene expression classifier of AML heterogeneity captures patient-specific variation in leukemia cell composition and predicts clinical responses to treatment.

The role of norepinephrine (NE) and acetylcholine (ACh) signaling in the cognitive control of impulsivity remains unclear. Here, the authors reveal that impulse control depends on phase synchrony between NE and ACh dynamics in the prefrontal cortex.

By combining genome sequencing and antibody binding (to all common pneumococcal proteins) data, Croucher et al. present a high-resolution analysis of the emergence of immune responses in children that can protect against pneumonia.

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.

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 number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

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.

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.

A robust mass spectrometry workflow was developed for rapid drug perturbation profiling in multiple cell lines, enabling improved mechanistic deconvolution of single compounds and revealing novel mechanisms of action.

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.

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

Adenosine-to-inosine editing is a form of RNA modification observed in the human brain transcriptome. Here the authors question the accuracy of utilizing postmortem samples to reflect the RNA biology of living brains. This is due to significant differences in adenosine-to-inosine editing between living and postmortem brain tissues, with most sites exhibiting higher editing levels postmortem.

ATG9A is transmembrane autophagic machinery protein that delivers phospholipids to expanding autophagosomes. Mailler et al. show that ATG9A is required to mobilize lipids from lipid droplets for autophagosome expansion as well as mitochondrial fatty acid import and β-oxidation.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Rebecca Fitzgerald and colleagues report whole-genome sequence analyses of 23 paired samples of Barrett's esophagus and esophageal adenocarcinoma. Their analyses of the clonal architecture of these lesions shows that copy number increases and heterogeneity persists during development of esophageal adenocarcinoma.

A multi-omics approach reveals host–microbiome interactions in aging in mice.

A first-in-human phase I clinical trial demonstrates the feasibility and safety of non-viral precision genome-engineering of a personalized adoptive cell transfer anticancer therapeutic.

Gao, Nowak-Imialek, Chen et al. generate porcine and human stem cells that possess expanded developmental potency for both embryonic and extra-embryonic cell lineages.

Offline cortical reactivations predict the gradual drift and separation in sensory cortical response patterns and may enhance sensory discrimination.

Lipid droplets (LDs) and peroxisomes are both generated by budding off the endoplasmic reticulum (ER). Here, the authors show that the yeast protein Pex30 marks ER subdomains where both LD and peroxisome biogenesis occurs, and identify MCTP2 as the putative mammalian Pex30 ortholog.

Archaeogenetic study of ancient DNA from medieval northwestern Europeans reveals substantial increase of continental northern European ancestry in Britain, suggesting mass migration across the North Sea during the Early Middle Ages.