VariantHunter: a method and tool for fast detection of emerging SARS-CoV-2 variants

With the progression of the COVID-19 pandemic, large datasets of SARS-CoV-2 genome sequences were collected to closely monitor the evolution of the virus and identify the novel variants/strains. By analyzing genome sequencing data, health authorities can 'hunt' novel emerging variants of SARS-CoV-2 as early as possible, and then monitor their evolution and spread. We designed VariantHunter, a highly flexible and user-friendly tool for systematically monitoring the evolution of SARS-CoV-2 at global and regional levels. In VariantHunter, amino acid changes are analyzed over an interval of 4 weeks in an arbitrary geographical area (continent, country, or region); for every week in the interval, the prevalence is computed and changes are ranked based on their increase or decrease in prevalence. VariantHunter supports two main types of analysis: lineage-independent and lineage-specific. The former considers all the available data and aims to discover new viral variants. The latter evaluates specific lineages/viral variants to identify novel candidate designations (sub-lineages and sub-variants). Both analyses use simple statistics and visual representations (diffusion charts and heatmaps) to track viral evolution. A dataset explorer allows users to visualize available data and refine their selection. VariantHunter is a web application free to all users. The two types of supported analysis (lineage-independent and lineage-specific) allow user-friendly monitoring of the viral evolution, empowering genomic surveillance without requiring any computational background. Database URL http://gmql.eu/variant_hunter/

HaploCoV: unsupervised classification and rapid detection of novel emerging variants of SARS-CoV-2

AbstractAccurate and timely monitoring of the evolution of SARS-CoV-2 is crucial for identifying and tracking potentially more transmissible/virulent viral variants, and implement mitigation strategies to limit their spread. Here we introduce HaploCoV, a novel software framework that enables the exploration of SARS-CoV-2 genomic diversity through space and time, to identify novel emerging viral variants and prioritize variants of potential epidemiological interest in a rapid and unsupervised manner. HaploCoV can integrate with any classification/nomenclature and incorporates an effective scoring system for the prioritization of SARS-CoV-2 variants. By performing retrospective analyses of more than 11.5 M genome sequences we show that HaploCoV demonstrates high levels of accuracy and reproducibility and identifies the large majority of epidemiologically relevant viral variants - as flagged by international health authorities – automatically and with rapid turn-around times.Our results highlight the importance of the application of strategies based on the systematic analysis and integration of regional data for rapid identification of novel, emerging variants of SARS-CoV-2. We believe that the approach outlined in this study will contribute to relevant advances to current and future genomic surveillance methods

Adducin- and Ouabain-Related Gene Variants Predict the Antihypertensive Activity of Rostafuroxin. Part 2: Clinical Studies

Twenty years of genetic studies have not contributed to improvement in the clinical management of primary arterial hypertension. Genetic heterogeneity, epistatic-environmental-biological interactions, and the pathophysiological complexity of hypertension have hampered the clinical application of genetic findings. In the companion article, we furnished data from rodents and human cells demonstrating two hypertension-triggering mechanisms--variants of adducin and elevated concentrations of endogenous ouabain (within a particular range)--and their selective inhibition by the drug rostafuroxin. Here, we have investigated the relationship between variants of genes encoding enzymes for ouabain synthesis [LSS (lanosterol synthase) and HSD3B1 (hydroxy-\u3b4-5-steroid dehydrogenase, 3\u3b2- and steroid \u3b4-isomerase 1)], ouabain transport {MDR1/ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1]}, and adducin activity [ADD1 (adducin 1) and ADD3], and the responses to antihypertensive medications. We determined the presence of these variants in newly recruited, never-treated patients. The genetic profile defined by these variants predicted the antihypertensive effect of rostafuroxin (a mean placebo-corrected systolic blood pressure fall of 14 millimeters of mercury) but not that of losartan or hydrochlorothiazide. The magnitude of the rostafuroxin antihypertensive effect was twice that of antihypertensive drugs recently tested in phase 2 clinical trials. One-quarter of patients with primary hypertension display these variants of adducin or concentrations of endogenous ouabain and would be expected to respond to therapy with rostafuroxin. Because the mechanisms that are inhibited by rostafuroxin also underlie hypertension-related organ damage, this drug may also reduce the cardiovascular risk in these patients beyond that expected by the reduction in systolic blood pressure alone

Adducin- and ouabain-related gene variants predict the antihypertensive activity of rostafuroxin, part 2: clinical studies

Twenty years of genetic studies have not contributed to improvement in the clinical management of primary arterial hypertension. Genetic heterogeneity, epistatic-environmental-biological interactions, and the pathophysiological complexity of hypertension have hampered the clinical application of genetic findings. In the companion article, we furnished data from rodents and human cells demonstrating two hypertension-triggering mechanisms-variants of adducin and elevated concentrations of endogenous ouabain (within a particular range)-and their selective inhibition by the drug rostafuroxin. Here, we have investigated the relationship between variants of genes encoding enzymes for ouabain synthesis [LSS (lanosterol synthase) and HSD3B1 (hydroxy-δ-5-steroid dehydrogenase, 3β- and steroid δ-isomerase 1)], ouabain transport {MDR1/ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1]}, and adducin activity [ADD1 (adducin 1) and ADD3], and the responses to antihypertensive medications. We determined the presence of these variants in newly recruited, never-treated patients. The genetic profile defined by these variants predicted the antihypertensive effect of rostafuroxin (a mean placebo-corrected systolic blood pressure fall of 14 millimeters of mercury) but not that of losartan or hydrochlorothiazide. The magnitude of the rostafuroxin antihypertensive effect was twice that of antihypertensive drugs recently tested in phase 2 clinical trials. One-quarter of patients with primary hypertension display these variants of adducin or concentrations of endogenous ouabain and would be expected to respond to therapy with rostafuroxin. Because the mechanisms that are inhibited by rostafuroxin also underlie hypertension-related organ damage, this drug may also reduce the cardiovascular risk in these patients beyond that expected by the reduction in systolic blood pressure alone.status: publishe