Search

NIPBL perturbation activates long terminal repeat (LTR)-derived alternative promoters due to reorganization of chromatin’s hierarchical structure, leading to LTR co-option and oncogene activation in melanoma cell lines.

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.

A rare variant burden analytical framework for Mendelian diseases was developed and applied to data from the 100,000 Genomes Project, identifying 69 probable new disease–gene associations.

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.

Psoriasis is a chronic inflammatory disease characterized by cutaneous manifestations, which can also have systemic effects on joints, the cardiovascular system and metabolism. In this Primer, Armstrong et al. review the epidemiology, pathophysiology, diagnosis and management of psoriasis, and highlight the quality of life of patients and future research areas.

An approach to estimate the contribution of all alleles to phenotypic variation is applied to transcription regulation using whole-genome sequencing and transcriptome data. Ultrarare variants contribute approximately 46% of cis heritability across genes.

White-tailed deer are an important reservoir of SARS-CoV-2 in the USA and continued monitoring of the virus in deer populations is needed. In this genomic epidemiology study from Ohio, the authors show that the virus has been introduced multiple times to deer from humans, and that it has evolved faster in deer.

This study presents the genomes of 2,101 emm28 Streptococcus pyogenes invasive strains, of which 492 were transcriptionally profiled, and 50 were assessed for virulence. GWAS, eQTL analysis, and study of isogenic mutant strains identified an intergenic region that alters global transcript profiles and bacterial virulence.

By performing a global RNA-RNA interactome analysis in hypervirulent Klebsiella pneumoniae, the authors identify the small RNA ArcZ targets many capsule genes and a key virulence factor MlaA, inhibiting Klebsiella infection and pathogenesis in mice.

Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.

A natural product containing an acylsulfenic acid functional group was discovered in a marine Streptomyces bacterium. Its biosynthesis is orchestrated by enzymes from both primary and secondary metabolism, including a flavin-dependent S-hydroxylase. The prevalence of enzymes catalysing the production of acylsulfenic acid in bacteria implies a potentially broad distribution of this functional group in specialized metabolites.

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).

Leveraging genomic and epidemiological surveillance data, the authors show that flu epidemics in the US arise from independent outbreaks in different states that spread from state to state through commuting and compete for susceptible hosts.

Biller et al. use long-read sequencing of fractionated ocean nanoparticles, showing that extracellular vesicles and virus-like particles contain distinct pools of genetic information and thus may differentially contribute to horizontal gene transfer dynamics in the ocean.

There are limited in vitro and in vivo models to study human fetal exposure to environmental noise. Here, the authors develop a computational model to quantify fetal exposure to acoustic fields, obtaining acoustic transfer characteristics across the human audio range.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

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.

Exome sequencing data from 60,706 people of diverse geographic ancestry is presented, providing insight into genetic variation across populations, and illuminating the relationship between DNA variants and human disease.

New Zealand implemented stringent COVID-19 control measures early after identification of its first case. Here, the authors perform whole genome sequencing of samples taken until 22 May 2020 and find high viral diversity indicative of multiple separate introductions and limited community transmission.

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.

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

An analysis of 38 ancient genomes from the aurochs, the extinct ancestor of modern cattle, provides insight into the population ancestry and domestication of this species.

Genomic analyses in individuals with index and familial intracranial aneurysms and experiments in vertebrate models identify pathogenic variants in the PPIL4 gene implicated in cerebral angiogenesis and cerebrovascular integrity, through the Wnt signaling pathway.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Using epigenome-wide mediation analyses to investigate DNA methylation as a path between adversity and depression, the authors found 31 cytosine–guanine dinucleotides (CpGs) associated with risk and 39 CpGs associated with protective effects.

Rare variant association analysis of plasma proteins using whole-genome sequencing data in 54,306 individuals in the UK Biobank demonstrates that combining both single-variant and aggregate testing will be needed for noncoding variant analysis.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Classification of archaeal and bacterial viruses can be automated with an algorithm that identifies relationships on the basis of shared gene content.

The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of subjects with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, they found that ∼20% of schizophrenia loci have variants that may contribute to altered gene expression and liability.

A multimodal analysis of patients with 22 different immune-mediated monogenic diseases versus matched healthy controls leads to the development of the immune health metric, which could be implemented broadly to predict responses to aging, vaccination and other immune perturbations.

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.

Whole-exome sequencing identifies ten risk genes for schizophrenia implicated by rare protein-coding variants, a subset of which overlap with risk genes in other neurodevelopmental disorders.

A study shows that cross-reactivity of microbial antigens and self-antigens presented by HLA-B*27 may be important in the pathogenesis of diseases associated with HLA-B*27 and identifies the shared binding motif responsible.

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.

Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.

Last year the first map of single nucleotide changes was published; now an international consortium has mapped even larger areas of differences, called copy number variants. These variants are at least 1,000-base-pair differences between individual people, and have been linked to both benign and disease-causing changes in the human genome.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Genomic epidemiology reveals multiple travel-related introductions of SARS-CoV-2 from mainland Europe into Scotland during the first wave of COVID-19.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Wolf Reik and Ian Dunham and colleagues cloned and sequenced the complete IGF2-H19 locus in tammar wallaby, a marsupial. Functional analyses revealed conservation of imprinting mechanisms, including germline DNA methylation, between marsupials and eutherians.