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Genomic analyses of human populations in the Pacific provide insights into the peopling history of the region and reveal episodes of biological adaptation relating to the immune system and lipid metabolism through introgression from archaic hominins and polygenic adaptation.

In this study of protein-coding de novo mutations in schizophrenia, researchers found only a small contribution toward overall risk, coming predominantly from genes under negative selection and highly expressed in the brain.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

The spatial location and sequence of DNA barcodes are detected with high sensitivity in fixed tissues.

PPM1D is a known mediator of p53 signalling, and has been linked to treatment resistance in glioma. In this work, the authors utilise genomics, proteomics, and mouse models to determine the role of PPM1D in the development of diffuse midline glioma.

Here the authors describe a simple reverse genetics method that relies on overlapping cDNA fragments for generation of positive-strand viruses including SARS-CoV-2 and characterize them in vitro and in vivo.

Cerebral malaria infection can provoke fatal neuroinflammation. Gros and colleagues identify an ubiquitin-modification axis that exacerbates neuroinflammation and that involves TRIM25 and USP15, which jointly promote type I interferon production.

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.

Paul de Bakker, Cisca Wijmenga and colleagues report on The Genome of the Netherlands Project, including whole-genome sequencing of 769 individuals of Dutch ancestry from 250 parent-offspring families and construction of a phased haplotype map. Their intermediate-coverage population sequencing data set provides a complementary resource to other publicly available data sets, including the 1000 Genomes Project.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Antibiotic-resistant bacteria are an urgent threat to human health. Here, Roberts et al. characterise and monitor an ongoing hospital outbreak of carbapenemase-producing Enterobacter hormaechei by integrating several technologies for whole-genome sequencing and shotgun metagenomics.

The genetic basis of gastric cancer, the fourth most common cancer worldwide, remains poorly understood. Here, the authors sequence and analyse the exomes and transcriptomes of primary gastric tumours and cell lines, and identify a ZAK kinase isoform that may have an oncogenic role in gastric cancer.

Here, Martiniano et al. examine the genetic structure of northern Britain in the late BC/early AD using ancient genome sequencing of 9 individuals. They uncover evidence of far-reaching Roman and later Anglo-Saxon migrations within a background of Britons similar to the earlier Iron Age.

In a randomized clinical trial, treatment using a monoclonal antibody targeting interleukin-6 (IL-6) in patients with cardiovascular disease and/or diabetes who were receiving maintenance kidney dialysis reduced levels of inflammatory biomarkers at 12 weeks, including C-reactive protein, paving the way for a phase 3 trial.

A multivariate genome-wide association study identifies 203 signals associated with facial variation. These signals are enriched for enhancer activity in cranial neural crest cells and craniofacial tissues.

Using unique barcodes for tumour cells, the authors explore the dynamics of human glioblastoma subpopulations, and suggest that clonal heterogeneity emerges through stochastic fate decisions of a neutral proliferative hierarchy.

The role of wild elk in the spread and persistence of bovine brucellosis in the Great Yellowstone area is unclear. Here, Kamath et al. analyse the genomic sequences of 245 Brucella abortusisolates from elk, bison and cattle, supporting the idea that elk is an important reservoir and source of livestock infections.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.

The largely unexplored strong-field QED regime in high-field science could be probed using high-energy particle beams and high-intensity lasers. Here the authors propose a concept to probe strong-field QED by harnessing the interaction between an ultrarelativistic electron beam and a solid and whose setup is based on the collision between the high-density beam and the self-fields reflected at the plasma boundary.

Michael Bamshad and colleagues report an exome sequencing study of extreme phenotypes to identify genetic variants that modify the risk for chronic Pseudomonas aeruginosa airway infection in individuals with cystic fibrosis.

Dominic Kwiatkowski and colleagues report analysis of genetic variation in 826 Plasmodium falciparum samples collected from 10 locations in West Africa and southeast Asia. They characterize the population structure of this parasite in Cambodia and find evidence for multiple distinct subpopulations showing high levels of genetic differentiation and artemisinin resistance.

Evolutionary steering uses therapies to control tumour evolution by exploiting trade-offs. Here, using a barcoding approach applied to large cell populations, the authors explore evolutionary steering in lung cancer cells treated with EGFR inhibitors.

Site-specific recombination and CRISPR-Cas9 have been used to generate genetically engineered mouse models of cancer. Here the authors compare sarcomas generated using both systems and see similar genetic and cellular phenotypes, suggesting CRISPR-Cas9 can be used to rapidly generate sarcoma models.

Analysis of benthic foraminiferal δ¹⁸O profiles from sediment cores in two depth transects in the Northwest Atlantic suggests that the subtropical gyre was deeper and stronger during the Last Glacial Maximum compared with today.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

The millimetre image of the Centaurus A nucleus by the Event Horizon Telescope reveals a highly collimated, asymmetrically edge-brightened jet. The source’s event horizon shadow should be visible at terahertz frequencies, consistent with the universal scale invariance of black holes.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

A large-scale meta-analysis across eight biobank datasets identifies common genetic variants associated with mosaic loss of the X chromosome in female participants.

Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.

Ferrando and colleagues analyze matched diagnostic and relapsed acute lymphocytic leukemia by whole-genome sequencing, and perform in vitro genome-wide CRISPR screens, to examine alterations associated with chemotherapy resistance.

The common bedbug is a pest for humans, yet its molecular biology is poorly understood. Here, the authors sequence the common bedbug genome and profile gene expression across all life stages to show major changes in gene expression after feeding on human blood.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Anna-Elina Lehesjoki and colleagues report exome sequencing of 84 cases of progressive myoclonus epilepsy (PME) and targeted resequencing of an additional 28 cases. They identify de novo mutations in KCNC1 in 13 cases and mutations in genes not previously associated with PME, including PRNP, SACS and TBC1D24, in additional cases.

Michael Talkowski and colleagues examine karyotypically balanced genomic rearrangement landscapes in the germline at single-nucleotide resolution. They find predominant roles for complex reorganization and non-homologous repair in such 'chromothripsis' processes, suggesting a mechanism of template switching and blunt-end ligation.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Sequencing of over 600 genes in a large collection of lung adenocarcinoma samples provides an overview of somatic mutations and signalling pathways altered in cancer genes in this tumour type.

In a large multi-cancer cohort, a single liquid biopsy assay enables the detection of four epigenomic modifications, allowing the monitoring of expression of potential drug targets and resistance genes.

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

The blind mole rat (BMR), Spalax galili, is perfectly adapted to life underground. Here, the authors sequence the BMR genome and transcriptome and highlight genomic features that may have played a role in adaptation to extreme underground stressors, such as darkness hypercapnia and hypoxia.

The herbicide propyzamide increases inflammation in the small and large intestine, and the AHR–NF-κB–C/EBPβ signalling axis—which operates in T cells and dendritic cells to promote intestinal inflammation—is targeted by propyzamide.

Ancient Salmonella enterica genomes from Neolithic Eurasian humans compared with those from later archaeological contexts illuminate the evolving host specificity of the pathogen from an initial multi-mammalian adaptation towards an increasingly human specialization.

John Chambers and colleagues report a genome-wide association study for type 2 diabetes in individuals of south Asian ancestry. They identify six loci newly associated with type 2 diabetes.