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A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

Mitochondrial networks are carefully positioned to facilitate energy distribution within muscle cells. Here they show that energetic demands and conserved transcription factors regulate mitochondrial network organization and contractile phenotypes independently in Drosophila.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

While the genetic basis of heart failure has been explored by genetic studies, the differences between subtypes are not well understood. Here, the authors performed genetic analyses on the two major subtypes of heart failure in a large biobank with genetic and health record data, finding unique genetic architecture for each subtype.

Basal-like breast cancer is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. Here the authors provide evidence that ID4 is a key controller of mammary stem/progenitor cell self-renewal, acting upstream of Notch signalling to repress luminal fate commitment.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

The authors compare the whole-genome expression profiles of peri-infarct neurons that show axonal sprouting after stroke to their non-sprouting neighbors. They describe a 'sprouting transcriptome' and perform further gain- and loss-of-function studies, finding novel roles in sprouting for a DNA-modifying molecule, a growth factor, and inhibitory myelin receptors.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Evolutionary modelling shows that an initial set of inhibitory neurons serving olfactory bulbs may have been repurposed to diversify the taxonomy of interneurons found in the expanded striata and cortices in primates.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

A new Burden of Proof meta-analytic method that accounts for between-study heterogeneity and corrects for bias between different study designs is used to interpret the strength of evidence between different pairs of risk factors and health outcomes.

Impaired Aβ clearance in late-onset Alzheimer’s disease (AD) affects progression. Here, the authors show that CD14 + CD16+ monocytes carry Aβ in peripheral circulation and CSF in AD, suggesting a role in Aβ clearance.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

This study reveals an important chondrocytic progenitor population for maintenance of adult articular cartilage marked by Gremlin 1. Loss of these progenitors causes osteoarthritis and suggests methods to sustain them may be effective future targets for management of osteoarthritis.

Azacitidine (AZA) response in myelodysplastic neoplasms is unpredictable. Here, the authors show in a phase 2 trial that while global methylation changes did not differ by response, baseline and initial CpG methylation differences in HSPCs predicted AZA response.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Rodin and Dou et al. characterized genome-wide somatic mutation in autistic and control brains, revealing that even unaffected individuals may possess dozens of brain somatic mutations and providing insight into the role of somatic mutation in autism.

UCP1 is involved in regulating thermogenesis, and the Ucp1-Cre mouse line has been widely used for studying brown fat. Here they show that this mouse line carries an extra copy of the Ucp1 gene and displays unexpected changes in fat tissue function. Researchers should be cautious when interpreting studies using this model.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Using genetically engineered models, Genovese and colleagues study patterns of convergent evolution in renal cancer, and pinpoint dysregulation of interferon signaling as a means of adaptation to chromosomal instability in metastatic progression.

Understanding the energy cost of entanglement extraction has fundamental implications, in particular for quantum field theory and condensed matter. Here, the authors analyse how the optimal energy cost scales with the number of extracted EPR pairs, when local operations and classical communication are allowed.

A study reveals that Fusobacterium nucleatum subspecies animalis is bifurcated into two distinct clades, and shows that only one of these dominates the colorectal cancer niche, probably through increased colonization of the human gastrointestinal tract.

The process of cellular engineering is rapidly accelerating owing to advances in technologies to manipulate DNA and other biomolecules, giving rise to the field of synthetic biology. A meeting was held in August 2005 to present progress in the field and to discuss topics in ethics, safety and security.

Large sequences are integrated site specifically into the human genome without double-strand DNA cleavage.

Deubiquitinating enzymes are involved in multiple cellular processes, including cell viability. The authors reveal a role for the deubiquitinating enzyme, USP17, in the migration of cells in response to chemokines and show that USP17 is required for the relocalization of GTPases involved in cell motility.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Understanding genomic variation in Plasmodium falciparum parasites and inferring migration patterns can guide malaria elimination strategies. Using genome-wide data for 1722 parasites collected from 54 districts, the authors use identity-by-descent approaches to estimate regional parasite migration and spread of artemisinin drug resistance.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

The intercalated disc (ICD) is a membrane structure of the cardiac muscle involved in normal heart function. Here the authors report that knockdown of the ICD-bound transmembrane protein 65 results in impaired ICD structure, abnormal cardiac electrophysiology and cardiomyopathy in mice.

Magnetotactic bacteria use intracellular chains of ferrimagnetic nanocrystals, produced within magnetosome organelles, to align and navigate along the geomagnetic field. Here, Wan et al. identify two proteins involved in magnetosome positioning in Magnetospirillum magneticum, homologs of which are widespread among magnetotactic bacteria.

Survey of postzygotic mosaic mutations (PZMs) in 5,947 trios with autism spectrum disorders (ASD) discovers differences in mutational properties between germline mutations and PZMs. Spatiotemporal analyses of the PZMs also revealed the association of the amygdala with ASD and implicated risk genes, including recurrent potential gain-of-function mutations in SMARCA4.

Terman and colleagues employed a genetic screen in Drosophila to identify the SelR methionine sulfoxide reductase as the enzyme responsible for reversing the Mical-mediated oxidation of actin. Thus, SelR antagonizes the effects of Semaphorin–Plexin–Mical-dependent signalling in vivo.

Expression of MHC class I molecules on motor neurons protects them from astrocyte-induced toxicity in ALS.

Attosecond electron pulse trains in electron microscopy are demonstrated through the coupling of phase-locked multicolour optical fields with electron pulses. A new variant of quantum state tomography for free-electron ensembles is established.

Repeat expansion disorders are found in all major global populations, and their frequency is up to three times higher than typically quoted, suggesting underdiagnosis or incomplete penetrance.

The characterization of miR-380-5p–driven p53 repression provides a new mechanism for downmodulation of stress-induced antiproliferative responses in wild-type p53 contexts, including embryonic stem cells and neuroblastoma tumors. miR-380-5p potentiates Ras-induced mammary gland tumorigenesis and is frequently elevated in human neuroblastomas. miR-380-5p inactivation induces tumor cell death and shows therapeutic efficacy in orthotopic neuroblastoma models.

Many pathogens manipulate ubiquitin-mediated signaling to evade host cell defense. Here, the authors characterize the structure and enzymatic activity of a deubiquitylase domain from the causative pathogen of scrub typhus, providing evidence for a distinct mechanism of ubiquitin chain selectivity.

Here the authors use single cell profiling of T cells across the human lifespan to show that a suboptimal TCR shift in T cells as we enter older age results in a molecular signature that resembles that of T cells from newborns and children.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.