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Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Here the authors show the prefrontal cortex simultaneously predicts context, the thoughts of others and future changes, while the precuneus acts as a hub to fuse these into a coherent experience.

How neural responses to boundaries develop in the subiculum remains unknown. Here authors show that the receptive fields of Boundary Vector Cells (neurons signalling vector displacement to boundaries) are altered by environment geometry, with directional tunings aligning with square arena walls, including during development.

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.

Complement proteome engagement is strongly linked to kidney outcomes in diabetes. This translational study leveraged five cohorts of over 4,500 person-years and high-throughput proteomics to enable potential biomarker-guided drug development.

APOBEC mutational signatures are commonly found in multiple cancer types. Here, the authors utilize multi-omics analyses to reveal that the cooccurrence of APOBEC associated mutagenesis and tobacco-smoking-related mutations affects lung tumor evolution and age at onset of lung cancer from smokers.

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.

Outbreaks of Middle East respiratory syndrome coronavirus in humans are driven by spillover from camels, and vaccines for camels are in development. Here, the authors use mathematical modelling to explore transmission dynamics in camels and investigate potential impacts of vaccines.

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.

Successful navigation relies on reciprocal transformation between different reference frames. Here the authors report egocentric representations of the angle and distance to the boundaries and center of the environment in rodent medial entorhinal cortex, previously known to contain only allocentric spatial representations.

Transcriptome-wide m⁶A RNA methylation profile in 162 primary prostate tumors identifies m⁶A association with prognostic clinical features and disease aggression.

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.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

Lentiviral massively parallel reporter assay (lentiMPRA) analysis of cardiac cis-regulatory elements characterizes the effects of noncoding de novo variants identified in congenital heart disease. EpiCard is a model for variant prioritization.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

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.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

Hu et al. discovered that the truncated form of human epidermal growth factor receptor 2 (HER2), called p95HER2, drives tumor progression and resistance to the antibody–drug conjugate trastuzumab deruxtecan in HER2⁺ breast cancer. Blocking p95HER2 restores antitumor immunity.

Human enhancers contain a high density of sequence features that are required for their normal in vivo function.

Mouse tracking can reveal people’s subjective beliefs and whether they understand the structure of a task. These data demonstrate that people often do not use this information to make good choices.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

The relationship between post-recovery COVID-19 and incident heart failure has not been investigated at scale. Here, the authors use electronic health records for ~600,000 patients in the US and find a higher rate of post-discharge incident heart failure in those hospitalised with COVID-19 than without.

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.

During the antigen-dependent phase of B cell development, clones expressing high-affinity B cell receptors are transferred from light zones to dark zones of germinal centers, while transforming their energy metabolism. Here authors show that in the light zones, the hypoxic microenvironment promotes growth arrest and apoptosis in B cells, while miR-155 protects the high-affinity clones via inducing a switch in energy utilization.

Many recent proteomics studies use either Olink or SomaScan platforms to quantify proteins in high-throughput, but the consistency between the two is unclear. Here, the authors measure proteins in the same samples using both platforms, finding only modest correlation, and compare associations with genetic variants and disease.

A regional atlas of the ageing human brain—spanning six distinct anatomical regions from individuals with and without Alzheimer’s dementia—provides insights into cellular vulnerability, response and resilience to Alzheimer’s disease pathology

Disease-monitoring in large vessel vasculitis is challenging, often leading to a mismatch between disease activity and treatment intensity. Here, the authors show that PET/MRI scanning can distinguish active from inactive large vessel vasculitis and track disease longitudinally, potentially allowing more stratified treatment for patients.

Here, the authors show that signal transducer and activator of transcription 3 (STAT3) has dual functions in small cell lung cancer as its deletion inhibited primary tumor growth but boosted metastatic spread. These seemingly opposing functions are a result of the requirement of STAT3 for stimulator of interferon genes–interferon signaling in metastasis and the authors show how it can be targeted in mice.

Base editing of the pathogenic trinucleotide repeat expansions underlying Huntington’s disease and Friedreich’s ataxia introduces repeat interruptions that reduce somatic expansion in patient cells and mice.

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.

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 multi-omic atlas of breast cancers, integrating single-cell RNA sequencing, spatial transcriptomics and immunophenotyping, identifies nine ecotypes associated with cellular heterogeneity and prognosis.

Colonization of continents by plants some 430 Myr ago enhanced the complexity of weathering and sedimentary systems, and altered the composition of continental crust, according to statistical assessment of zircon compositions.

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.

This multisite study detects a link between brain dynamic functional network connectivity and current and future post-traumatic stress symptom severity with a stronger effect in the female group.

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.

SARS-CoV-2 variant-specific neutralizing antibodies (nAbs) mediate protection against infection by the cognate variant to distinct extents, while the majority of protection elicited by natural infection is not mediated by nAbs.

Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.

The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Secondary organic aerosols in Beijing are driven by emissions from outside of the city, with seasonally different emission sources, according to molecular chemical characterization of particulate air pollution.

A secure framework that harmonizes storage and querying of clinical and genetic data using blockchain technology was developed to support combined genotype–phenotype queries, improving transparency into how and when health information is used.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

The fornix is the major fiber tract connecting the medial temporal lobe and the medial diencephalon. This structural imaging study of individuals with fornix atropy finds that the fornix is important for recall, but not recognition, consistent with the idea that hippocampal inputs are selectively important for recall, rather than recognition.

Whole-genome sequencing analyses of African populations provide insights into continental migration, gene flow and the response to human disease, highlighting the importance of including diverse populations in genomic analyses to understand human ancestry and improve health.

Multiplexed error-robust fluorescence in situ hybridization (MERFISH) together with deep-learning-based nucleus segmentation enabled the construction of a highly detailed and informative spatially resolved single-cell atlas of human fetal cortical development.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.