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Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

The sustainability of the majority of multispecies reef fisheries around the globe remains unassessed. This study provides context-specific sustainable reference points for coral reef fish using environmental conditions. Using these reference points, they show that most reef fish stocks have failed at least one fisheries sustainability benchmark.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Polycystic ovary syndrome (PCOS) is a common disorder, the causes of which remain incompletely understood. Here the authors report the discovery of gene regulatory mechanisms that help to explain genetic associations with PCOS in the GATA4, FSHB and DENND1A loci.

Excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity and, in turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif that supports decision-making.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

In colorectal cancer, therapeutic resistance is driven by MAPK-dependent epithelial cell plasticity.

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.

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.

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

Graham and colleagues analyzed locally advanced esophageal adenocarcinoma clinical trial patient samples and identified major changes in gene expression profiles and immune microenvironment composition independent of changes in clonal composition.

Spatially resolved transcriptome analysis of human and mouse idiopathic pulmonary fibrosis identifies disease-associated niches and a role for aberrant alveolar epithelial cells in human disease pathogenesis.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

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.

Statins are promising for breast cancer therapy; dipyridamole can potentiate their effects, but is contraindicated in some cases. Here, the authors develop a pharmacogenomics pipeline to predict other compounds that potentiate statins, and validate the top candidates in cell line screens and 3D cultures.

The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

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 authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Osteocytes are the master regulatory cells within the skeleton. Here, the authors map the transcriptome of osteocytes from diverse skeletal sites, ages and between sexes and identify an osteocyte transcriptome signature associated with rare skeletal disorders and common complex skeletal diseases.

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.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

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.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

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.

Obesity has been reported to promote tumourigenesis and chemoresistance but the underlying mechanisms are not completely understood. Here, the authors show that adipocytes induce Galectin-9 (GAL-9) expression in B-acute lymphoblastic leukaemia (B-ALL) cells which leads to chemoresistance and antibody-mediated blockade of GAL-9 increases survival in preclinical B-ALL murine models.

Immune dN/dS is the ratio of nonsynonymous to synonymous mutations in the MHC-bound immunopeptidome. Application of immune dN/dS to cancer datasets shows that it distinguishes immune evasion and escape and predicts response to immunotherapies.

The mitotic ages of breast tumors can be inferred from fluctuating CpG DNA methylation, with higher epigenetic entropy in older cancers.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Inflammatory skin diseases are frequently associated with dysregulation of cutaneous immunity. Here the authors perform human challenge with house dust mite allergen in patients with atopic dermatitis and explore the molecular network determining tolerance versus inflammation and identify a role for metallothioneins in the modulation of allergen induced inflammation.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Findings from an umbrella review of more than 100 meta-analyses suggest that screen time can have both positive and negative associations with educational and health outcomes for youth, but effect sizes are small.

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.

Alterations in the tumour microenvironment (TME) can contribute to prostate cancer progression, but it is unclear how tumours mediate those changes. Here, analysis of human prostate cancer tissues and key stages of prostate cancer progression in a genetically engineered mouse model using single-cell RNA-sequencing reveals the central role of MYC signalling in reprogramming the TME.

Induction of CD4 T follicular helper (Tfh) cells is important for antibody responses to viral infections. Here, the authors show in a rhesus macaque model of mild COVID-19 that SARS-CoV-2 infection results in transient accumulation of proliferating Tfh cells with a Th1 profile in peripheral blood and generation of germinal center Tfh cells specific for viral proteins.

David van Heel and colleagues report results of a large genome-wide association study of celiac disease. Most of the associated loci contain genes with immune functions, and over half harbor risk variants that are correlated with variation in cis gene expression.

In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

An analysis of fish and macroinvertebrate communities in European rivers over 32 years shows that inland ship traffic is associated with declining taxonomic richness, diversity and trait richness and with increased taxonomic evenness.

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.