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Markov Chains

A visual explanation by Victor Powell/w text by Lewis Lehe
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Virology and Bioinformatics from Virology.ca
Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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It's a group effort - the curators:

It's a group effort - the curators: | Virology and Bioinformatics from Virology.ca | Scoop.it

get in touch if you want to help curate this topic

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PolyCTLDesigner: a computational tool for constructing polyepitope T-cell antigens - BMC Research Notes

Construction of artificial polyepitope antigens is one of the most promising strategies for developing more efficient and safer vaccines evoking T-cell immune responses. Epitope rearrangements and utilization of certain spacer sequences have been proven to greatly influence the immunogenicity of polyepitope constructs. However, despite numerous efforts towards constructing and evaluating artificial polyepitope immunogens as well as despite numerous computational methods elaborated to date for predicting T-cell epitopes, peptides binding to TAP and for antigen processing prediction, only a few computational tools were currently developed for rational design of polyepitope antigens.

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Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge : Nature Medicine : Nature Publishing Group

A chimpanzee adenovirus-based vaccination approach elicits acute and long-term protection against ebolavirus challenge in nonhuman primates.

Via Mel Melendrez-Vallard
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Emerging Viral Diseases: Confronting Threats with New Technologies

Abstract

Emerging viral diseases pose ongoing health threats, particularly in an era of globalization; however, new biomedical research technologies such as genome sequencing and structure-based vaccine and drug design have improved our ability to respond to viral threats.

 
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Rabies Rapid Transit System

Rabies Rapid Transit System | Virology and Bioinformatics from Virology.ca | Scoop.it
Rabies virus hijacks the transport systems of neurons, manipulating axonal transport machinery to get to the central nervous system at maximum speed.
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Reverse genetics system could ease norovirus research

Reverse genetics system could ease norovirus research | Virology and Bioinformatics from Virology.ca | Scoop.it
Finding may allow scientists to manipulate viral genome.
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Major alteration in coxsackievirus B3 genomic RNA structure distinguishes a virulent strain from an avirulent strain

Coxsackievirus B3 (CV-B3) is a cardiovirulent enterovirus that utilizes a 5′ untranslated region (5′UTR) to complete critical viral processes. Here, we directly compared the structure of a 5′UTR from a virulent strain with that of a naturally occurring avirulent strain. Using chemical probing analysis, we identified a structural difference between the two 5′UTRs in the highly substituted stem-loop II region (SLII). For the remainder of the 5′UTR, we observed conserved structure. Comparative sequence analysis of 170 closely related enteroviruses revealed that the SLII region lacks conservation. To investigate independent folding and function, two chimeric CV-B3 strains were created by exchanging nucleotides 104–184 and repeating the 5′UTR structural analysis. Neither the parent SLII nor the remaining domains of the background 5′UTR were structurally altered by the exchange, supporting an independent mechanism of folding and function. We show that the attenuated 5′UTR lacks structure in the SLII cardiovirulence determinant.

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MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1

The IFN-α-inducible restriction factor MxB blocks HIV-1 infection after reverse transcription but prior to integration. Genetic evidence suggested that capsid is the viral determinant for restriction by MxB. This work explores the ability of MxB to bind to the HIV-1 core, and the role of capsid-binding in restriction

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TWiV 301: Marine viruses and insect defense

TWiV 301: Marine viruses and insect defense | Virology and Bioinformatics from Virology.ca | Scoop.it
Vincent speaks with Carla and Curtis about RNA interference and antiviral defense in fruit flies, and viruses in the sea, the greatest biodiversity on Earth.

Via Ed Rybicki
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Inferring Heterogeneous Evolutionary Processes Through Time: from Sequence Substitution to Phylogeography

Molecular phylogenetic and phylogeographic reconstructions generally assume time-homogeneous substitution processes. Motivated by computational convenience, this assumption sacrifices biological realism and offers little opportunity to uncover the temporal dynamics in evolutionary histories. Here, we propose an evolutionary approach that explicitly relaxes the time-homogeneity assumption by allowing the specification of different infinitesimal substitution rate matrices across different time intervals, called epochs, along the evolutionary history. We focus on an epoch model implementation in a Bayesian inference framework that offers great modeling flexibility in drawing inference about any discrete data type characterized as a continuous-time Markov chain, including phylogeographic traits. To alleviate the computational burden that the additional temporal heterogeneity imposes, we adopt a massively parallel approach that achieves both fine- and coarse-grain parallelization of the computations across branches that accommodate epoch transitions, making extensive use of graphics processing units. Through synthetic examples, we assess model performance in recovering evolutionary parameters from data generated according to different evolutionary scenarios that comprise different numbers of epochs for both nucleotide and codon substitution processes. We illustrate the usefulness of our inference framework in two different applications to empirical data sets: the selection dynamics on within-host HIV populations throughout infection and the seasonality of global influenza circulation. In both cases, our epoch model captures key features of temporal heterogeneity that remained difficult to test using ad hoc procedures. [Bayesian inference; BEAGLE; BEAST; Epoch Model; phylogeography; Phylogenetics.]

 
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Genomic analysis of vaccinia virus strain TianTan provides new insights into the evolution and evolutionary relationships between Orthopoxviruses

Genomic analysis of vaccinia virus strain TianTan provides new insights into the evolution and evolutionary relationships between Orthopoxviruses | Virology and Bioinformatics from Virology.ca | Scoop.it

Vaccinia virus (VACV) strain TianTan was used for much of China's modern history to vaccinate against smallpox, however the only genome sequence contains errors. We have sequenced additional examples of TianTan to obtain a better picture of this important virus. We detected two different subclones. One (TP03) encodes large deletions in the terminal repeats that extend into both VEGF genes and create a small plaque variant. The second clone (TP05) encodes a nearly intact complement of genes in the terminal repeats, except for an insertion of sequences resembling the telomeric 69 bp repeats. The TP05 genome spans 196,260 bp and encodes 219 genes. The revised sequence documents the integrity of all the genes in the conserved virus core. Phylogenetic methods show that TianTan belongs to a unique clade of VACV, but probably also share a common origin with strains belonging to the Copenhagen/Lister lineage and distinct from the Wyeth/Dryvax lineage.

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Changes in the hemagglutinin of H5N1 viruses during human infection – Influence on receptor binding

Changes in the hemagglutinin of H5N1 viruses during human infection – Influence on receptor binding | Virology and Bioinformatics from Virology.ca | Scoop.it
Abstract

As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process.

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GuavaH: a compendium of host genomic data in HIV biology and disease - Retrovirology

GuavaH: a compendium of host genomic data in HIV biology and disease - Retrovirology | Virology and Bioinformatics from Virology.ca | Scoop.it
AbstractBackground

There is an ever-increasing volume of data on host genes that are modulated during HIV infection, influence disease susceptibility or carry genetic variants that impact HIV infection. We created GuavaH (Genomic Utility for Association and Viral Analyses in HIV, http://www.GuavaH.orgwebcite), a public resource that supports multipurpose analysis of genome-wide genetic variation and gene expression profile across multiple phenotypes relevant to HIV biology.

Findings

We included original data from 8 genome and transcriptome studies addressing viral and host responses in and ex vivo. These studies cover phenotypes such as HIV acquisition, plasma viral load, disease progression, viral replication cycle, latency and viral-host genome interaction. This represents genome-wide association data from more than 4,000 individuals, exome sequencing data from 392 individuals, in vivo transcriptome microarray data from 127 patients/conditions, and 60 sets of RNA-seq data. Additionally, GuavaH allows visualization of protein variation in ~8,000 individuals from the general population. The publicly available GuavaH framework supports queries on (i) unique single nucleotide polymorphism across different HIV related phenotypes, (ii) gene structure and variation, (iii) in vivo gene expression in the setting of human infection (CD4+ T cells), and (iv) in vitro gene expression data in models of permissive infection, latency and reactivation.

Conclusions

The complexity of the analysis of host genetic influences on HIV biology and pathogenesis calls for comprehensive motors of research on curated data. The tool developed here allows queries and supports validation of the rapidly growing body of host genomic information pertinent to HIV research.

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SearchSmallRNA: a graphical interface tool for the assemblage of viral genomes using small RNA libraries data - Virology Journal

SearchSmallRNA: a graphical interface tool for the assemblage of viral genomes using small RNA libraries data - Virology Journal | Virology and Bioinformatics from Virology.ca | Scoop.it
Next-generation parallel sequencing (NGS) allows the identification of viral pathogens by sequencing the small RNAs of infected hosts. Thus, viral genomes may be assembled from host immune response products without prior virus enrichment, amplification or purification. However, mapping of the vast information obtained presents a bioinformatics challenge.
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Ten Simple Rules for Better Figures

Ten Simple Rules for Better Figures | Virology and Bioinformatics from Virology.ca | Scoop.it

"Scientific visualization is classically defined as the process of graphically displaying scientific data. However, this process is far from direct or automatic. There are so many different ways to represent the same data: scatter plots, linear plots, bar plots, and pie charts, to name just a few. Furthermore, the same data, using the same type of plot, may be perceived very differently depending on who is looking at the figure. A more accurate definition for scientific visualization would be a graphical interface between people and data. In this short article, we do not pretend to explain everything about this interface; rather, see [1], [2] for introductory work. Instead we aim to provide a basic set of rules to improve figure design and to explain some of the common pitfalls."

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ImmunizeCA App - Immunize Canada

ImmunizeCA App - Immunize Canada | Virology and Bioinformatics from Virology.ca | Scoop.it
The Canadian Public Health Association, Immunize Canada and the Ottawa Hospital Research Institute collaborated to develop an app for mobile devices that will help Canadians keep track of their vaccinations. The app is FREE and can be downloaded from iTunes, Google Play of BlackBerry World.
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Microbiology: Bacteria get vaccinated

Microbiology: Bacteria get vaccinated | Virology and Bioinformatics from Virology.ca | Scoop.it
Infection by defective bacterial viruses that cannot replicate has now been found to be the key feature enabling bacteria to rapidly develop adaptive immunity against functional viruses.
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A fish, a rabbit — same thing, to a creationist

A fish, a rabbit — same thing, to a creationist | Virology and Bioinformatics from Virology.ca | Scoop.it
JBS Haldane is said to have responded to a question about how evolution could be disproved by saying, “A Precambrian rabbit”. What was meant by this, of course, is any substantial discovery that greatly disrupted the evidence for the chronological pattern of descent observed in Earth’s life. That pattern of descent is one of the…
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A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection | Virology and Bioinformatics from Virology.ca | Scoop.it

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.

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Human Immunodeficiency Virus gag and protease: partners in resistance

Human Immunodeficiency Virus gag and protease: partners in resistance | Virology and Bioinformatics from Virology.ca | Scoop.it

Human Immunodeficiency Virus (HIV) maturation plays an essential role in the viral life cycle by enabling the generation of mature infectious virus particles through proteolytic processing of the viral Gag and GagPol precursor proteins. An impaired polyprotein processing results in the production of non-infectious virus particles. Consequently, particle maturation is an excellent drug target as exemplified by inhibitors specifically targeting the viral protease (protease inhibitors; PIs) and the experimental class of maturation inhibitors that target the precursor Gag and GagPol polyproteins. Considering the different target sites of the two drug classes, direct cross-resistance may seem unlikely. However, coevolution of protease and its substrate Gag during PI exposure has been observed both in vivo and in vitro. This review addresses in detail all mutations in Gag that are selected under PI pressure. We evaluate how polymorphisms and mutations in Gag affect PI therapy, an aspect of PI resistance that is currently not included in standard genotypic PI resistance testing. In addition, we consider the consequences of Gag mutations for the development and positioning of future maturation inhibitors.

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Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: a systematic review of the literature - BMC Infectious Diseases

Background

The potential impact of an influenza pandemic can be assessed by calculating a set of transmissibility parameters, the most important being the reproduction number (R), which is defined as the average number of secondary cases generated per typical infectious case.

Methods

We conducted a systematic review to summarize published estimates of R for pandemic or seasonal influenza and for novel influenza viruses (e.g. H5N1). We retained and summarized papers that estimated R for pandemic or seasonal influenza or for human infections with novel influenza viruses.

Results

The search yielded 567 papers. Ninety-one papers were retained, and an additional twenty papers were identified from the references of the retained papers. Twenty-four studies reported 51 R values for the 1918 pandemic. The median R value for 1918 was 1.80 (interquartile range [IQR]: 1.47-2.27). Six studies reported seven 1957 pandemic R values. The median R value for 1957 was 1.65 (IQR: 1.53-1.70). Four studies reported seven 1968 pandemic R values. The median R value for 1968 was 1.80 (IQR: 1.56-1.85). Fifty-seven studies reported 78 2009 pandemic R values. The median R value for 2009 was 1.46 (IQR: 1.30-1.70) and was similar across the two waves of illness: 1.46 for the first wave and 1.48 for the second wave. Twenty-four studies reported 47 seasonal epidemic R values. The median R value for seasonal influenza was 1.28 (IQR: 1.19-1.37). Four studies reported six novel influenza R values. Four out of six R values were <1.

Conclusions

These R values represent the difference between epidemics that are controllable and cause moderate illness and those causing a significant number of illnesses and requiring intensive mitigation strategies to control. Continued monitoring of R during seasonal and novel influenza outbreaks is needed to document its variation before the next pandemic.

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Ecology and evolution of viruses infecting uncultivated SUP05 bacteria

Ecology and evolution of viruses infecting uncultivated SUP05 bacteria | Virology and Bioinformatics from Virology.ca | Scoop.it

Viruses modulate microbial communities and alter ecosystem functions. However, due to cultivation bottlenecks specific virus-host interaction dynamics remain cryptic. Here we examined 127 single-cell amplified genomes (SAGs) from uncultivated SUP05 bacteria isolated from a marine oxygen minimum zone (OMZ) to identify 69 viral contigs representing five new genera within dsDNACaudoviralesand ssDNAMicroviridae. Infection frequencies suggest that ~1/3 of SUP05 bacteria are viral-infected, with higher infection frequency where oxygen-deficiency was most severe. ObservedMicroviridaeclonality suggests recovery of bloom-terminating viruses, while systematic co-infection between dsDNA and ssDNA viruses posits previously unrecognized cooperation modes. Analyses of 186 microbial and viral metagenomes revealed that SUP05 viruses persisted for years, but remained endemic to the OMZ. Finally, identification of virus-encoded dissimilatory sulfite reductase suggests SUP05 viruses reprogram their host's energy metabolism. Together these results demonstrate closely coupled SUP05 virus-host co-evolutionary dynamics with potential to modulate biogeochemical cycling in climate-critical and expanding OMZs.

 


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nucleotides · genome assembler benchmarking

An assembler catalogue: continuous, objective and reproducible evaluation of genome assemblers using docker containers
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The origins of giant viruses, virophages and their relatives in host genomes

Giant viruses have revealed a number of surprises that challenge conventions on what constitutes a virus. The Samba virus newly isolated in Brazil expands the known distribution of giant mimiviruses to a near-global scale. These viruses, together with the transposon-related virophages that infect them, pose a number of questions about their evolutionary origins that need to be considered in the light of the complex entanglement between host, virus and virophage genomes.

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Closing the loop: from paper to protein annotation using supervised Gene Ontology classification

Gene function curation of the literature with Gene Ontology (GO) concepts is one particularly time-consuming task in genomics, and the help from bioinformatics is highly requested to keep up with the flow of publications. In 2004, the first BioCreative challenge already designed a task of automatic GO concepts assignment from a full text. At this time, results were judged far from reaching the performances required by real curation workflows. In particular, supervised approaches produced the most disappointing results because of lack of training data. Ten years later, the available curation data have massively grown. In 2013, the BioCreative IV GO task revisited the automatic GO assignment task. For this issue, we investigated the power of our supervised classifier, GOCat. GOCat computes similarities between an input text and already curated instances contained in a knowledge base to infer GO concepts. The subtask A consisted in selecting GO evidence sentences for a relevant gene in a full text. For this, we designed a state-of-the-art supervised statistical approach, using a naïve Bayes classifier and the official training set, and obtained fair results. The subtask B consisted in predicting GO concepts from the previous output. For this, we applied GOCat and reached leading results, up to 65% for hierarchical recall in the top 20 outputted concepts. Contrary to previous competitions, machine learning has this time outperformed standard dictionary-based approaches. Thanks to BioCreative IV, we were able to design a complete workflow for curation: given a gene name and a full text, this system is able to select evidence sentences for curation and to deliver highly relevant GO concepts. Contrary to previous competitions, machine learning this time outperformed dictionary-based systems. Observed performances are sufficient for being used in a real semiautomatic curation workflow. GOCat is available at http://eagl.unige.ch/GOCat/.

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A histidine residue of the influenza virus hemagglutinin controls the pH dependence of the conformational change mediating membrane fusion. J Virol. 2014

Abstract

The conformational change of the influenza virus hemagglutinin (HA) protein mediating the fusion between the virus envelope and the endosomal membrane was hypothesized to be induced by protonation of specific histidine residues since their pKa matches the pH of late endosomes (pKa∼6.0). However, such critical key histidine residues remain to be identified. We investigated the highly conserved His184 at the HA1-HA1 interface and His110 at the HA1-HA2 interface of highly pathogenic H5N1 HA as potential pH sensors. By replacing both histidines by different amino acids and analyzing the effect of these mutations on conformational change and fusion we found that His184, but not His110, plays an essential role for the pH dependence of conformational change of HA. Computational modeling of the protonated His184 revealed that His184 is central of a conserved interaction network possibly regulating the pH dependence of conformational change via its pKa. As the propensity of histidine to get protonated largely depends on its local environment, mutation of residues in vicinity of histidine may affect its pKa. HA of highly pathogenic H5N1 viruses carries a Glu-to-Arg mutation at position 216 close to His184. By mutation of residue 216 in the highly as well as the low pathogenic H5 HA we observed a significant influence on the pH dependence of conformational change and fusion. These results are in support of a pKa modulating effect by neighboring residues.

IMPORTANCE:

The main pathogenic determinant of influenza viruses, the hemagglutinin (HA) protein, triggers a key step of the infection process: the fusion of the virus envelope with the endosomal membrane releasing the viral genome. Whereas essential aspects of the fusion inducing mechanism of HA at low pH are well understood, the molecular trigger of the pH dependent conformational change inducing fusion has been unclear. We provide evidence that His184 regulates the pH dependence of the HA conformational change via its pKa. Mutations of neighboring residues which may affect the pKa of His184 could play an important role of virus adaptation to a specific host. We suggest that mutation of neighboring residue 216, which is present in all highly pathogenic phenotypes of H5N1 influenza strains, contributed to the adaptation of these viruses to the human host via its effect on the pKa of His184.

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