Search

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Here Yan et al. assess the community dynamics that are driving biodiversity-ecosystem function relationships across the world’s reef fishes. While reef fish abundances and species richness have similar impacts on productivity in temperate regions, productivity in the tropics is driven by abundances.

In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.

Sears and colleagues found that ongoing replication stress pathways and T cell clonal responses differentiate liver and lung recurrence and are associated with different clinical outcomes in the context of pancreatic ductal adenocarcinoma.

Grazing affects plant diversity, but plant diversity in turn may modulate the effect of grazing on the plant community. This global analysis explores the association between plant species richness and plant cover resistance to grazing intensity in drylands.

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.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

Evidence synthesized from 252 large-herbivore exclusion studies suggests that herbivore-induced change in dominance, independent of site productivity or precipitation, best predicts herbivore effects on biodiversity in grassland and savannah sites.

Inventory data from 90 lowland Amazonian forest plots and a phylogeny of 526 angiosperm genera were used to show that taxonomic and phylogenetic diversity are both predictive of wood productivity but not of biomass variation.

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.

Here, using samples from ~1,100 individuals, the authors define the nasal microbiome linked to Staphylococcus aureus colonization, identifying seven communities- either S. aureus-dominated or dominated by other bacteria.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

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.

Species synchrony is considered a major mechanism of biodiversity–ecosystem stability relationships. Here, by combining theory, modelling and empirical work, the authors show that with time series length species synchrony decreases and its relationship with diversity switches from positive to negative.

Immune features and T cell characteristics that correlate with post-intervention control of HIV-1 viraemia inform the development of combination immunotherapies that may enhance the ability to elicit durable HIV remission.

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.

In this work, authors report a mechanism for how phage can promote the spread of costly antibiotic resistance. They show that faster-growing sensitive cells dominate the biomass periphery where they encounter more phage, allowing for slower growing resistant cells to persist.

Neoadjuvant therapies with dual anti-HER2 blockade have proven effective in HER2⁺ breast cancer treatment. Here, the authors develop a score that integrates antigen receptor repertoire features and clinical parameters to predict prognosis after anti-HER2 neoadjuvant treatments.

Cities may host surprisingly diverse and functionally distinct biological communities. This global analysis on 5302 vertebrate and invertebrate species finds evidence of 4 trait syndromes in urban animal assemblages, modulated by spatial and geographic factors.

SIDISH integrates single-cell and bulk RNA sequencing data using deep learning to identify high-risk cell populations and prognostic biomarkers, enabling in silico perturbations that could guide precision therapeutics and advance personalized medicine.

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.

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 molecular and cellular underpinnings of cribriform prostate cancer aggressiveness remain to be explored. Here, the authors perform single-cell RNA-sequencing, TCR sequencing and histology and reveal cancer cell intrinsic pathways and an immunosuppressive tumour microenvironment.

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.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

Analysis of human genotypes and 16S microbiome data of 18,473 individuals from 25 cohorts through a genome-wide association study, a phenome-wide association study and Mendelian randomization identifies host genetic and microbial trait associations.

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

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

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.

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.

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.

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.

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.

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.

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.

Computational and experimental analyses of the effects of spatial partitioning in microbial communities identify correlations between biodiversity and spatial context, offering experimental guidance for maintaining microbial community structures.