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Rebecca Fitzgerald and colleagues report whole-genome sequence analyses of 23 paired samples of Barrett's esophagus and esophageal adenocarcinoma. Their analyses of the clonal architecture of these lesions shows that copy number increases and heterogeneity persists during development of esophageal adenocarcinoma.

New research finds that policymakers coleading energy scenario design has the potential both to better align scenarios with policymakers’ priorities and to question current policy, by substantially reducing energy use at half of the cost of technology-focused approaches.

Dr Barrett examines the likely development of the chemical industry during this decade. Any assessment of current and likely future trends must take into account the fact that the industry is not a unified whole; it comprises several principal sectors, each operating in a distinct manner. But the industry's most outstanding feature has, nevertheless, been dynamic growth.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

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.

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).

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.

Spillover of avian influenza H5N1 from birds to mammals have been increasingly detected, but reports of cases in humans remain limited. Here, the authors find serological evidence of human exposure to influenza H5N1 in Malaysian Borneo, an important stopover site for migratory shorebirds.

Carl Anderson, Jeffrey Barrett and colleagues use whole-genome sequencing and imputation to explore the genetic architecture of inflammatory bowel disease. They identify a low-frequency missense variant in ADCY7 that doubles risk of ulcerative colitis and detect a burden of very rare, damaging missense variants in known Crohn's disease risk genes.

Co-design of energy transition pathways with policymakers and the public lead to more significant demand-side reductions than current supply-side-focused policy. When policymakers work directly with academics to re-consider how and why we use energy in our everyday lives, politically feasible, significantly cheaper options with 45% less energy demand are possible.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

It is known that invasive lung adenocarcinomas evolve from pre-cancerous dysplastic lesions. In this study, the authors show that evolution of pre-cancerous lesions is accompanied by DNA methylation alterations, and that global hypomethylation correlates with immune infiltration, mutational burden and copy number alterations.

The end-Permian is associated with major changes in both marine and terrestrial biodiversity. Here, Gastaldo et al. present high resolution dating of the Lystrosaurus Assemblage Zone in the Karoo Basin, South Africa, demonstrating that the marine crisis did not mirror a coeval event on land.

The practical optimizations of heterogeneous catalytic processes and reactor engineering are intertwined, but often what occurs inside the reactor remains elusive. Now, the molecular diffusion and carbon number of hydrocarbon products during Fischer–Tropsch synthesis on a Ru/TiO₂ catalyst are spatially resolved via magnetic resonance imaging in a pilot-scale fixed-bed reactor.

Metabolic imaging offers promise for improving the characterisation of prostate cancer phenotypes of varying clinical significance. Here, the authors show distinct metabolic features of cribriform and non-cribriform lesions using a variety of imaging techniques across scales.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Results of fine-mapping 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals and several new fine-mapping methods.

The chemical honokiol is found in the bark of magnolia trees, which are used for traditional medicine in Asian countries. Here, Pillai et al, show honokiol protects the heart from hypertrophic remodelling in mice, and even reverses established cardiac hypertrophy, by activating the deacetylase Sirt3.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

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.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

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.

Jeffrey Barrett, Carl Anderson and colleagues report the results of a large genome-wide association study of inflammatory bowel disease. They identify 25 new genome-wide significant loci, 3 of which contain integrin genes, and find that the associated variants at several of these loci are correlated with expression changes in response to immune stimulus.

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.

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.

Mark Daly and colleagues present results of a combined analysis of data from three recent genome-wide association studies for Crohn's disease, followed by replication in a large independent sample collection. Their results confirm 11 previously reported risk loci and provide genome-wide significant evidence for 21 new loci associated with the disease.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Whole-exome sequencing in a large autism study identifies over 100 autosomal genes that are likely to affect risk for the disorder; these genes, which show unusual evolutionary constraint against mutations, carry de novo loss-of-function mutations in over 5% of autistic subjects and many function in synaptic, transcriptional and chromatin-remodelling pathways.

The large-scale study of protein expression and protein function by using molecular technologies—proteomics—has become increasingly attractive, because the proteome reflects the intrinsic genetic program of the cell and the impact of its immediate environment. This Review describes conventional proteomic technologies currently being used and their limitations, and demonstrates their clinical applicability, with specific reference to published data of relevance to the gastroenterology field.

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

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

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.

Miles Parkes and colleagues report results of a large genome-wide association meta-analysis and replication study for Crohn's disease. They identify 30 new susceptibility loci for this inflammatory bowel disease and implicate several interesting candidate genes in disease pathogenesis.