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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.

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.

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).

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

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 goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Thompson et al. report clinical outcomes and immunological correlates of a phase 1 trial of a peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma.

The Connectome Annotation Versioning Engine (CAVE) is a platform for proofreading, annotating and analyzing datasets reaching the petascale. Currently, CAVE is used for electron microscopy datasets, but it can potentially be used for other large-scale 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.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Two complementary studies used whole-genome sequencing of single cell-derived hematopoietic colonies to show that chemotherapy results in a marked decrease in hematopoietic stem and progenitor cell (HSPC) diversity, with the parallel evolution of multiple independent HSPCs harboring mutations in DNA damage response genes.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

Systematic comparison of genome-wide association results for disease risk and disease-specific mortality for nine common diseases across seven biobanks finds limited overlap between genetic effects on disease susceptibility and survival.

Neural Decomposition (NEURD) is a software package that decomposes neuronal data from high-resolution electron microscopy volumes into feature-rich graph representations to facilitate analysis for neuroscience research.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Anti-NMDA receptor encephalitis is a severe brain disorder caused by autoantibodies that trigger NMDA receptor loss. Here, the authors show that ART5803, a monovalent antibody, blocks this process and restores function in cell and primate models.

A study reports the development of a method to trace intercellular transfer of mitochondria, and demonstrates that cancer cells that receive mitochondria from neurons have enhanced metastatic capabilities.

Terrestrial ecosystem productivity is widely accepted to be nutrient limited. A series of standardized nutrient addition experiments, carried out on grasslands on five continents, suggests aboveground grassland productivity is commonly limited by multiple nutrients, including potassium and micronutrients.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Experimental models of breast cancer reveal the phosphoinositide-phosphatases PIPP and PTEN play non-redundant roles in suppressing mouse mammary epithelial cell transformation, and disease progression in a subset of human breast cancers.

Using volumetric electron microscopy, the authors map and analyze the structure of cortical inhibition with synaptic resolution across a column of visual cortex.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.