Ensembl’s 10th year

Ensembl (http://www.ensembl.org) integrates genomic information for a comprehensive set of chordate genomes with a particular focus on resources for human, mouse, rat, zebrafish and other high-value sequenced genomes. We provide complete gene annotations for all supported species in addition to specific resources that target genome variation, function and evolution. Ensembl data is accessible in a variety of formats including via our genome browser, API and BioMart. This year marks the tenth anniversary of Ensembl and in that time the project has grown with advances in genome technology. As of release 56 (September 2009), Ensembl supports 51 species including marmoset, pig, zebra finch, lizard, gorilla and wallaby, which were added in the past year. Major additions and improvements to Ensembl since our previous report include the incorporation of the human GRCh37 assembly, enhanced visualisation and data-mining options for the Ensembl regulatory features and continued development of our software infrastructure

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

PHYTO-THREATS:addressing threats to uk forests and woodlands from phytophthora; identifying risks of spread in trade and methods for mitigation

The multidisciplinary ‘Phyto-threats’ project was initiated in 2016 to address the increasing risks to UK forest and woodland ecosystems from trade-disseminated Phytophthora. A major component of this project was to examine the risk of Phytophthora spread through nursery and trade practices. Close to 4000 water and root samples were collected from plant nurseries located across the UK over a three-year period. Approximately half of the samples tested positive for Phytophthora DNA using a metabarcoding approach with 63 Phytophthora species identified across nurseries, including quarantine-regulated pathogens and species not previously reported in the UK. Phytophthora diversity within nurseries was linked to high-risk management practices such as use of open rather than closed water sources. Analyses of global Phytophthora risks identified biological traits and trade pathways that explained global spread and host range, and which may be of value for horizon-scanning. Phytophthoras having a higher oospore wall index and faster growth rates had wider host ranges, whereas cold-tolerant species had broader geographic and latitudinal ranges. Annual workshops revealed how stakeholder and sector ‘appetite’ for nursery accreditation increased over three years, although an exploratory cost-benefit analysis indicated that the predicted benefits of introducing best practice expected by nurseries outweigh their costs only when a wider range of pests and diseases (for example, Xylella) is considered. However, scenario analyses demonstrated the significant potential carbon costs to society from the introduction and spread of a new tree-infecting Phytophthora. Thus, the overall net benefit to society from nurseries adopting best practice could be substantial

Ensembl 2014

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Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

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