Pre-emptive genomic surveillance of emerging ebolaviruses.
Ontology highlight
ABSTRACT:
SUBMITTER: Postigo-Hidalgo I
PROVIDER: S-EPMC6988270 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Pre-emptive genomic surveillance of emerging ebolaviruses.
Postigo-Hidalgo Ignacio I Fischer Carlo C Moreira-Soto Andres A Tscheak Patricia P Nagel Michael M Eickmann Markus M Drexler Jan Felix JF
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 20200101 3
Genomic surveillance during ebolavirus outbreaks to elucidate transmission chains and develop diagnostic tests is delayed by the laborious development of variant-specific laboratory assays. We developed a new protocol combining 31 parallel PCR assays with Illumina/MinION-based sequencing, allowing generic ebolavirus genomic surveillance, validated using cell culture-derived Ebola, Reston, Sudan and Taï Forest virus at concentrations compatible with patient viral loads. Our approach enables pre-e ...[more]
Similar Datasets
Project description:Constructing effective and scalable protection strategies over epidemic propagation is a challenging issue. It has been attracting interests in both theoretical and empirical studies. However, most of the recent developments are limited to the simplified single-layered networks. Multiplex social networks are social networks with multiplelayers where the same set of nodes appear in different layers. Consequently, a single attack can trigger simultaneous propagation in all corresponding layers. Therefore, suppressing propagation in multiplex topologies is more challenging given the fact that each layer also has a different structure. In this paper, we address the problem of suppressing the epidemic propagation in multiplex social networks by allocating protection resources throughout different layers. Given a multiplex graph, such as a social network, and k budget of protection resources, we aim to protect a set of nodes such that the percentage of survived nodes at the end of epidemics is maximized. We propose MultiplexShield, which employs the role of graph spectral properties, degree centrality and layer-wise stochastic propagation rate to pre-emptively select k nodes for protection. We also comprehensively evaluate our proposal in two different approaches: multiplex-based and layer-based node protection schemes. Furthermore, two kinds of common attacks are also evaluated: random and targeted attack. Experimental results show the effectiveness of our proposal on real-world datasets.
| S-EPMC6214285 | biostudies-other
Project description:The propagation of epileptic seizure activity in the brain is a widespread pathophysiology that, in principle, should yield to intervention techniques guided by mathematical models of neuronal ensemble dynamics. During a seizure, neural activity will deviate from its current dynamical regime to one in which there are significant signal fluctuations. In silico treatments of neural activity are an important tool for the understanding of how the healthy brain can maintain stability, as well as of how pathology can lead to seizures. The hope is that, contained within the mathematical foundations of such treatments, there lie potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the dynamic causal modelling neuronal state equation generalises to a Fokker-Planck formalism if one extends the framework to model the ways in which activity propagates along the structural connections of neural systems. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity-i.e., by lowering the rate at which neuronal fluctuations disperse to neighbouring regions. We show, for neural systems prone to epileptic seizures, that such a reduction in diffusivity can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror the activity profile of a pathological region in its functionally connected areas. This counter-intuitive method is intended to be used pre-emptively-i.e., in order to mitigate the effects of the seizure, or ideally even prevent it from occurring in the first place. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network prior to seizure onset. Our hope is that this technique can form the basis for future real-time monitoring and intervention devices that are capable of treating epilepsy in a non-invasive manner.
| S-EPMC7732083 | biostudies-literature
Project description:Wheat (Triticum aestivum L.) is the most widely grown cereal crop in the world and is staple food to half the world's population. The current world population is expected to reach 9.8 billion people by 2050, but food production is not expected to keep pace with demand in developing countries. Significant opportunities exist for traditional grain exporters to produce and export greater amounts of wheat to fill the gap. Karnal bunt, however, is a major threat, due to its use as a non-tariff trade barrier by several wheat-importing countries. The cultivation of resistant varieties remains the most cost-effective approach to manage the disease, but in countries that are free of the disease, genetic improvement is difficult due to quarantine restrictions. Here we report a study on pre-emptive breeding designed to identify linked molecular markers, evaluate the prospects of genomic selection as a tool, and prioritise wheat genotypes suitable for use as parents. In a genome-wide association (GWAS) study, we identified six DArTseq markers significantly linked to Karnal bunt resistance, which explained between 7.6 and 29.5% of the observed phenotypic variation. The accuracy of genomic prediction was estimated to vary between 0.53 and 0.56, depending on whether it is based solely on the identified Quantitative trait loci (QTL) markers or the use of genome-wide markers. As genotypes used as parents would be required to possess good yield and phenology, further research was conducted to assess the agronomic value of Karnal bunt resistant germplasm from the International Maize and Wheat Improvement Center (CIMMYT). We identified an ideal genotype, ZVS13_385, which possessed similar agronomic attributes to the highly successful Australian wheat variety, Mace. It is phenotypically resistant to Karnal bunt infection (<1% infection) and carried all the favourable alleles detected for resistance in this study. The identification of a genotype combining Karnal bunt resistance with adaptive agronomic traits overcomes the concerns of breeders regarding yield penalty in the absence of the disease.
| S-EPMC8358121 | biostudies-literature
Project description:BACKGROUND:Artemisinin-based combination therapies are the first line of treatment for Plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in Southeast Asia over the past decade. Mutations in the kelch13 gene have been implicated in this resistance. We used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. We retrospectively sequenced the genomes of 194 P. falciparum isolates from five sites in Northwest Thailand, over the period of a rapid increase in the emergence of artemisinin resistance (2001-2014). RESULTS:We evaluate statistical metrics for temporal change in the frequency of individual SNPs, assuming that SNPs associated with resistance increase in frequency over this period. After Kelch13-C580Y, the strongest temporal change is seen at a SNP in phosphatidylinositol 4-kinase, which is involved in a pathway recently implicated in artemisinin resistance. Furthermore, other loci exhibit strong temporal signatures which warrant further investigation for involvement in artemisinin resistance evolution. Through genome-wide association analysis we identify a variant in a kelch domain-containing gene on chromosome 10 that may epistatically modulate artemisinin resistance. CONCLUSIONS:This analysis demonstrates the potential of a longitudinal genomic surveillance approach to detect resistance-associated gene loci to improve our mechanistic understanding of how resistance develops. Evidence for additional genomic regions outside of the kelch13 locus associated with artemisinin-resistant parasites may yield new molecular markers for resistance surveillance, which may be useful in efforts to reduce the emergence or spread of artemisinin resistance in African parasite populations.
| S-EPMC5410087 | biostudies-literature
Project description:We have investigated how birds avoid mid-air collisions during head-on encounters. Trajectories of birds flying towards each other in a tunnel were recorded using high speed video cameras. Analysis and modelling of the data suggest two simple strategies for collision avoidance: (a) each bird veers to its right and (b) each bird changes its altitude relative to the other bird according to a preset preference. Both strategies suggest simple rules by which collisions can be avoided in head-on encounters by two agents, be they animals or machines. The findings are potentially applicable to the design of guidance algorithms for automated collision avoidance on aircraft.
| S-EPMC5040264 | biostudies-literature
Project description:Patients with breast cancer often receive many drugs to manage the cancer, side effects associated with cancer treatment, and co-morbidities (i.e., polypharmacy). Drug-drug and drug-gene interactions contribute to the risk of adverse events (AEs), which could lead to non-adherence and reduced efficacy. Here we investigated several well-characterized inherited (germline) pharmacogenetic (PGx) targets in 225 patients with breast cancer. All relevant clinical, pharmaceutical, and PGx diplotype data were aggregated into a single unifying informatics platform to enable an exploratory analysis of the cohort and to evaluate pharmacy ordering patterns. Of the drugs recorded, there were 38 for which high levels of evidence for clinical actionability with PGx was available from the US FDA and/or the Clinical Pharmacogenetics Implementation Consortium (CPIC). These data were associated with 10 pharmacogenes: DPYD, CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP4F2, G6PD, MT-RNR1, SLCO1B1, and VKORC1. All patients were taking at least one of the 38 drugs and had inherited at least one actionable PGx variant that would have informed prescribing decisions if this information had been available pre-emptively. The non-cancer drugs with PGx implications that were common (prescribed to at least one-third of patients) included anti-depressants, anti-infectives, non-steroidal anti-inflammatory drugs, opioids, and proton pump inhibitors. Based on these results, we conclude that pre-emptive PGx testing may benefit patients with breast cancer by informing drug and dose selection to maximize efficacy and minimize AEs.
| S-EPMC7998388 | biostudies-literature
Project description:Transient phosphorylation of the alpha-subunit of translation initiation factor 2 (eIF2alpha) represses translation and activates select gene expression under diverse stressful conditions. Defects in the eIF2alpha phosphorylation-dependent integrated stress response impair resistance to accumulation of malfolded proteins in the endoplasmic reticulum (ER stress), to oxidative stress and to nutrient deprivations. To study the hypothesized protective role of eIF2alpha phosphorylation in isolation of parallel stress signaling pathways, we fused the kinase domain of pancreatic endoplasmic reticulum kinase (PERK), an ER stress-inducible eIF2alpha kinase that is normally activated by dimerization, to a protein module that binds a small dimerizer molecule. The activity of this artificial eIF2alpha kinase, Fv2E-PERK, is subordinate to the dimerizer and is uncoupled from upstream stress signaling. Fv2E-PERK activation enhanced the expression of numerous stress-induced genes and protected cells from the lethal effects of oxidants, peroxynitrite donors and ER stress. Our findings indicate that eIF2alpha phosphorylation can initiate signaling in a cytoprotective gene expression pathway independently of other parallel stress-induced signals and that activation of this pathway can single-handedly promote a stress-resistant preconditioned state.
| S-EPMC1271668 | biostudies-literature
Project description:The potential of the systemic antifungal treatment of non-immunocompromised patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown, although it represents three out of four antifungal treatments prescribed in intensive care units. It may allow an early treatment of invasive fungal infection at incubation phase, but exposes patients to unnecessary antifungal treatments with subsequent costs and antifungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered insufficient, the potential of this strategy needs to be demonstrated by a randomized controlled trial. Such a trial is currently ongoing.
| S-EPMC4335794 | biostudies-literature
Project description:Junior doctors are commonly asked to prescribe simple medications for symptom relief for patients out of hours. Unfortunately, time constraints and other pressures may lead to delays before the medications are prescribed. A quality improvement project was conducted at a large university teaching hospital to establish the extent of the problem, with the aim of finding measures to improve preemptive prescribing for patients. Baseline data was gathered over three busy wards to calculate the total of new prescriptions made over the course of a weekend. There were 24 new prescriptions required over the weekend, a percentage increase of 14.9% compared to the existing prescriptions on a Friday. Following the first intervention this decreased to 10.2%, and by the second intervention the rate was 4.9%. Data collected several months later confirmed that the interventions remained successful, and preemptive prescribing continued. Overall, our interventions have shown that the number of new prescriptions required out of hours can be reduced by educating junior doctors on preemptive prescribing.
| S-EPMC4949621 | biostudies-literature
Project description:This paper makes the case for immediate planning for a COVID-19 vaccination uptake strategy in advance of vaccine availability for two reasons: first, the need to build a consensus about the order in which groups of the population will get access to the vaccine; second, to reduce any fear and concerns that exist in relation to vaccination and to create demand for vaccines. A key part of this strategy is to counter the anti-vaccination movement that is already promoting hesitancy and resistance. Since the beginning of the COVID-19 pandemic there has been a tsunami of misinformation and conspiracy theories that have the potential to reduce vaccine uptake. To make matters worse, sections of populations in many countries display low trust in governments and official information about the pandemic and how the officials are tackling it. This paper aims to set out in short form critical guidelines that governments and regional bodies should take to enhance the impact of a COVID-19 vaccination strategy. We base our recommendations on a review of existing best practice guidance. This paper aims to assist those responsible for promoting COVID-19 vaccine uptake to digest the mass of guidance that exists and formulate an effective locally relevant strategy. A summary of key guidelines is presented based on best practice guidance.
| S-EPMC7459701 | biostudies-literature