Search

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).

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Heathland ecosystems are resistant to extreme wildfires due to the differing drivers of low fuel moisture across all fuel types, but extreme heatwaves can cause homogenously low moisture content across fuels, causing extreme fire behavior, according to field measurement analysis of Calluna vulgaris and organic soil moisture content across the UK.

This analysis of whole-genome sequencing data from 421 multiple myeloma samples elucidates the timing of key genomic events and shows associations between the timing of 1q gain and clinical outcome.

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.

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 authors show that aberrant epithelial GREM1 expression remodels intestinal stroma to form ectopic stem cell niches in mice. Anti-GREM1 reversed these changes, highlighting a potential strategy for preventing polyposis in patients with HMPS.

Progression from asymptomatic smoldering multiple myeloma (SMM) to symptomatic Multiple Myeloma occurs at different rates in different patients. Here, the authors report fewer NRAS and FAM46C mutations and adverse translocations in SMM compared to MM, while KRAS mutations are associated with a shorter time to progression.

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.

Using whole-genome and single-cell RNA sequencing data of patients with multiple myeloma treated with carfilzomib, lenalidomide, dexamethasone and daratumumab, Maura et al. identify distinct genomic drivers and microenvironment changes affecting outcome.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

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.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Many published studies of the current SARS-CoV-2 pandemic have analysed data from non-representative samples from populations. Here, using UK BioBank samples, Gibran Hemani and colleagues discuss the potential for such studies to suffer from collider bias, and provide suggestions for optimising study design to account for this.

The ages and geochemical compositions of inclusions of sublithospheric diamonds indicate additions to the mantle keel of Gondwana by the underplating of buoyant subducted material, originating from 300–700-km depth, which may have contributed to supercontinent stability during long-distance migration.

Richard Houlston, Gareth Morgan, Kari Hemminki and colleagues report the results of a genome-wide association study of multiple myeloma. They identify two regions influencing susceptibility to this hematological malignancy.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Previous genome-wide association studies have identified loci associated with the risk of multiple myeloma. Here, the authors present a meta-analysis of six genome wide association studies of the disease and identify eight new loci; functional studies identify genes as candidates for the basis of these associations.

A new inhibitor of Mycobacterium tuberculosis leucyl-tRNA synthetase is associated with bactericidal activity in humans and may be a candidate for combination therapy of tuberculosis.

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.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Multiple myeloma is a cancer of the plasma cells, and the complete aetiology of the disease is still unclear. Here the authors perform an additional GWAS analysis followed by a meta-analysis with existing GWAS and replication genotyping and identify 6 novel risk loci and utilise gene expression, epigenetic profiling and in situ Hi-C data to further our understanding of MM susceptibility.

FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Existing clinical models cannot fully capture smoldering multiple myeloma (SMM) heterogeneity. Here, integration of 42 genetic alterations from 214 SMM patients using an unsupervised binary matrix factorization clustering approach results in the identification of 6 distinct molecular and clinical subtypes.

Analysis of 1.32 billion records of medication data from England, Scotland and Wales reveals that the COVID-19 pandemic led to substantial declines in dispensing of antihypertensive and lipid-lowering medications, leading to increased risks for future cardiovascular disease.

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.

Spatially and temporally resolved data can improve our understanding of evolution and treatment resistance in multiple myeloma (MM). Here, the authors analyse spatial and longitudinal heterogeneity in MM patients using multi-region sequencing, and identify subclones associated with relapse and therapy resistance.

Richard Houlston, Kari Hemminki and colleagues report a meta-analysis of genome-wide association studies of multiple myeloma and identify a variant in the CCDN1 gene that influences risk for developing a specific tumor karyotype with the t(11;14)(q13;q32) translocation.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.