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PLOS Computational Biology: The Roots of Bioinformatics in ISMB

PLOS Computational Biology: The Roots of Bioinformatics in ISMB | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS Computational Biology is an open-access
Nicolas Palopoli's insight:

Besides the interesting recall of the Intelligent Systems for Molecular Biology (ISMB) annual conferences on computational biology, it offers a nice insight into current state-of-the-art methodologies and upcoming trends in the discipline.

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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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This topic is a collaborative effort:

This topic is a collaborative effort: | Virology and Bioinformatics from Virology.ca | Scoop.it
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Proteomic analysis at the subcellular level for host targets against influenza A virus (H1N1). - Antiviral Res. 2013

Influenza viruses (IVs) trigger a series of intracellular signaling events and induce complex cellular responses from the infected host cell. Accumulating evidence suggests that host cell proteins play an essential role in viral propagation and represent novel antiviral therapeutic targets. Subcellular proteomic technology provides a method for understanding regional differences at the protein level. The present study, which utilized subcellular proteomic technology, aimed to identify host cell proteins involved in influenza virus (HIN1) infection. Two-dimensional gel electrophoresis (2-DE) combined with mass spectrum (MS) was performed on protein extracts from the nuclei, cytoplasm, and mitochondria of infected and control human lung epithelial cells (A549). In total, 112 differentially expressed protein molecules were identified; 80 protein spots were successfully validated using MS. The differential expression of ISG15, MIF, PDCD5, and UCHL1 was confirmed by western blot. Furthermore, antisense oligodeoxyribonucleotide (ODN) targeting ISG15, MIF, PDCD5, and UCHL1 significantly mitigated HIN1 propagation, cytopathic effects, vRNA by RT-qPCR, and rescued cell viability in A549 cells. Taken together, the differentially expressed proteins identified in this study might provide novel targets for anti-influenza drug development.

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Media Availability: Genetic Defect May Confer Resistance to Certain Viral Infections

Media Availability: Genetic Defect May Confer Resistance to Certain Viral Infections | Virology and Bioinformatics from Virology.ca | Scoop.it
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Positive selection and evolution of dengue type-3 virus in the Indian subcontinent - J Vector Borne Dis. 2013

AbstractBACKGROUND:

Dengue virus infection has recently taken endemic proportions in India with dengu type-3 (DEN-3) as a predominant serotype. In this study, we carried out the selection pressure analysis of three critical immunogenic regions of DEN-3. Phylogenetic analysis was then carried out on the positively selected genomic region in the DEN-3 virus strains isolated in the Indian subcontinent over a time span of 25 yr (1984-2008). Bayesian Markov chain Monte Carlo (MCMC) calculation of the substitution rate was carried out for the DEN-3 genotype-III sequences.

METHODS:

Sequences corresponding to the C-prM, E-NS1 and NS1 sequence regions of DEN-3 strains were taken for the positive selection analysis. The C-prM junction sequences were then used to construct a maximum likelihood (ML) phylogenetic tree. Substitution rates were also calculated under various models of population growth.

RESULTS:

It was found that codon 86, corresponding to a conserved arginine residue in a crucial T-cell epitope of the C-protein was under significant positive selection. The K86R substitution was found to exist in almost all the Indian strains isolated after 2004. The ML tree constructed from the C-prM junction sequences indicated that strains from the 2006 dengue incidences in Delhi, namely: 04/03/del2006, 05/03/del2006, and 06/03/del2006 were the most rapidly evolving. Substitution rates of a DEN-3 genotype-III sequences from the Indian subcontinent were found to be ~3.0 times higher than those reported from other parts of the world.

CONCLUSION:

Positive selection in the codon corresponding to R86 of the highly conserved surface C-protein is important in view of its occurrence in a T-cell epitope as well as its strict conservation in all the DEN strains. Phylogenetic analysis of the C-prM junction sequences showed that three strains of 2006 are rapidly evolving. These results were also supported by calculations of the substitution rates. Their significance in the expansion of viral epidemics requires to be investigated.

  
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Measles Outbreak Traced to Fully Vaccinated Patient for First Time

Measles Outbreak Traced to Fully Vaccinated Patient for First Time | Virology and Bioinformatics from Virology.ca | Scoop.it

Get the measles vaccine, and you won’t get the measles—or give it to anyone else. Right? Well, not always. A person fully vaccinated against measles has contracted the disease and passed it on to others. The startling case study contradicts received wisdom about the vaccine and suggests that a recent swell of measles outbreaks in developed nations could mean more illnesses even among the vaccinated.

 

When it comes to the measles vaccine, two shots are better than one. Most people in the United States are initially vaccinated against the virus shortly after their first birthday and return for a booster shot as a toddler. Less than 1% of people who get both shots will contract the potentially lethal skin and respiratory infection. And even if a fully vaccinated person does become infected—a rare situation known as “vaccine failure”—they weren’t thought to be contagious.

 

That’s why a fully vaccinated 22-year-old theater employee in New York City who developed the measles in 2011 was released without hospitalization or quarantine. But like Typhoid Mary, this patient turned out to be unwittingly contagious. Ultimately, she transmitted the measles to four other people, according to a recent report in Clinical Infectious Diseases that tracked symptoms in the 88 people with whom “Measles Mary” interacted while she was sick. Surprisingly, two of the secondary patients had been fully vaccinated. And although the other two had no record of receiving the vaccine, they both showed signs of previous measles exposure that should have conferred immunity.

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Pandemic Influenza: The Perpetual Challenge

Pandemic Influenza: The Perpetual Challenge | Virology and Bioinformatics from Virology.ca | Scoop.it
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DNA nanobots deliver drugs in living cockroaches - health - 08 April 2014 - New Scientist

DNA nanobots deliver drugs in living cockroaches - health - 08 April 2014 - New Scientist | Virology and Bioinformatics from Virology.ca | Scoop.it

It's a computer – inside a cockroach. Nano-sized entities made of DNA that are able to perform the same kind of logic operations as a silicon-based computer have been introduced into a living animal.

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rougeforfire's curator insight, April 10, 4:54 PM

WOOOO !!!! Nanobots are here !!

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Targeted Prostaglandin E2 Inhibition Enhances Antiviral Immunity through Induction of Type I Interferon and Apoptosis in Macrophages: Immunity

Targeted Prostaglandin E2 Inhibition Enhances Antiviral Immunity through Induction of Type I Interferon and Apoptosis in Macrophages: Immunity | Virology and Bioinformatics from Virology.ca | Scoop.it
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Whooping cough bounces back | Science News

Whooping cough bounces back | Science News | Virology and Bioinformatics from Virology.ca | Scoop.it
A new type of pertussis vaccine introduced in the late 1990s may have led to the return of a disease that was nearly eradicated 40 years ago. Public opposition to vaccination hasn’t helped matters.
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Bananageddon: Millions face hunger as deadly fungus Panama disease decimates global banana crop

Bananageddon: Millions face hunger as deadly fungus Panama disease decimates global banana crop | Virology and Bioinformatics from Virology.ca | Scoop.it
Scientists have warned that the world’s banana crop, worth £26 billion and a crucial part of the diet of more than 400 million people, is facing “disaster” from virulent diseases immune to pesticides or other forms of control.
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Will omics help to cure the flu?

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Ed Rybicki's comment, April 14, 6:51 AM
Nah. Just like it won't help cure HIV, HCV, HBV....
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Antiviral strategies against influenza virus: towards new therapeutic approaches - Online First - Springer

Antiviral strategies against influenza virus: towards new therapeutic approaches - Online First - Springer | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza viruses are major human pathogens responsible for respiratory diseases affecting millions of people worldwide and characterized by high morbidity and significant mortality. Influenza infections can be controlled by vaccination and antiviral drugs. However, vaccines need annual updating and give limited protection. Only two classes of drugs are currently approved for the treatment of influenza: M2 ion channel blockers and neuraminidase inhibitors. However, they are often associated with limited efficacy and adverse side effects. In addition, the currently available drugs suffer from rapid and extensive emergence of drug resistance. All this highlights the urgent need for developing new antiviral strategies with novel mechanisms of action and with reduced drug resistance potential. Several new classes of antiviral agents targeting viral replication mechanisms or cellular proteins/processes are under development. This review gives an overview of novel strategies targeting the virus and/or the host cell for counteracting influenza virus infection.

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Inferring Influenza Infection Attack Rate from Seroprevalence Data

Inferring Influenza Infection Attack Rate from Seroprevalence Data | Virology and Bioinformatics from Virology.ca | Scoop.it

Seroprevalence survey is the most practical method for accurately estimating infection attack rate (IAR) in an epidemic such as influenza. These studies typically entail selecting an arbitrary titer threshold for seropositivity (e.g. microneutralization [MN] 1:40) and assuming the probability of seropositivity given infection (infection-seropositivity probability, ISP) is 100% or similar to that among clinical cases. We hypothesize that such conventions are not necessarily robust because different thresholds may result in different IAR estimates and serologic responses of clinical cases may not be representative. To illustrate our hypothesis, we used an age-structured transmission model to fully characterize the transmission dynamics and seroprevalence rises of 2009 influenza pandemic A/H1N1 (pdmH1N1) during its first wave in Hong Kong. We estimated that while 99% of pdmH1N1 infections became MN1:20 seropositive, only 72%, 62%, 58% and 34% of infections among age 3–12, 13–19, 20–29, 30–59 became MN1:40 seropositive, which was much lower than the 90%–100% observed among clinical cases. The fitted model was consistent with prevailing consensus on pdmH1N1 transmission characteristics (e.g. initial reproductive number of 1.28 and mean generation time of 2.4 days which were within the consensus range), hence our ISP estimates were consistent with the transmission dynamics and temporal buildup of population-level immunity. IAR estimates in influenza seroprevalence studies are sensitive to seropositivity thresholds and ISP adjustments which in current practice are mostly chosen based on conventions instead of systematic criteria. Our results thus highlighted the need for reexamining conventional practice to develop standards for analyzing influenza serologic data (e.g. real-time assessment of bias in ISP adjustments by evaluating the consistency of IAR across multiple thresholds and with mixture models), especially in the context of pandemics when robustness and comparability of IAR estimates are most needed for informing situational awareness and risk assessment. The same principles are broadly applicable for seroprevalence studies of other infectious disease outbreaks.

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Running mothur from within iPython

Running mothur from within iPython | Virology and Bioinformatics from Virology.ca | Scoop.it
ipython-mothurmagic - IPython extension for running mothur commands in an IPython notebook
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Constraints from protein structure and intra-molecu... [Virology. 2014] - PubMed - NCBI

A major challenge for developing effective treatments for HIV-1 is the viruses' ability to generate new variants. Inter-strain recombination is a major contributor to this high evolutionary rate, since at least 20% of viruses are observed to be recombinant. However, the patterns of recombination vary across the viral genome. A number of factors influence recombination, including sequence identity and secondary RNA structure. In addition the recombinant genome must code for a functional virus, and expressed proteins must fold to stable and functional structures. Any intragenic recombination that disrupts internal residue contacts may therefore produce an unfolded protein. Here we find that contact maps based on protein structures predict recombination breakpoints observed in the HIV-1 pandemic. Moreover, many pairs of contacting residues that are unlikely to be disrupted by recombination are coevolving. We conclude that purifying selection arising from protein structure and intramolecular coevolutionary changes shapes the observed patterns of recombination in HIV-1.

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Correction: Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals

Correction: Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals | Virology and Bioinformatics from Virology.ca | Scoop.it
From molecules to physiology
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Are Bats Spreading Ebola Across Sub-Saharan Africa?

The first cases went unrecognized. Ebola had never been seen in Guinea before, so when people became ill with fever, muscle pain, vomiting, and diarrhea, health workers initially assumed Lassa fever or yellow fever—both endemic in the region—were to blame. No one put the pieces together until late March. By then, the virus had been spreading for months. Now, health workers are struggling to contain the outbreak, which has already killed more than 100 and has affected at least two neighboring countries. At the same time, scientists are combing the forests, and the genome of the virus itself, looking for clues to how this strain—well known in Central Africa—ended up so far west, and whether its spread suggests people in forested areas all across sub-Saharan Africa are at risk.

 

Ebola is not a complete stranger to West Africa. In the mid-1990s, two outbreaks hit chimpanzees in Taï National Park in the Ivory Coast, and one researcher studying the animals was infected. (She survived.) "We expected to find the Taï strain," says Sylvain Baize, a virologist at the Institut Pasteur in Lyon, France, who with his colleagues sequenced some of the first samples of the virus from Guinea. To their surprise, it turned out to be Ebola Zaire, the deadliest of the five known Ebola species.

 

"We have no idea how it's moved from Central Africa to Guinea," says primatologist Christophe Boesch of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. A leading suspect is fruit bats. In Central African rainforests, several species have shown evidence of infection with Ebola without getting sick. And at least one of the species, the little collared fruit bat, Myonycteris torquata, has a range that stretches as far west as Guinea. "We've always been very suspicious of bats," says William Karesh of EcoHealth Alliance in New York City, who studies the interactions among humans, animals, and infectious diseases.

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Ed Rybicki's curator insight, April 14, 6:50 AM

Thanks Torben Barsballe!

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BEAST 2: A Software Platform for Bayesian Evolutionary Analysis

BEAST 2: A Software Platform for Bayesian Evolutionary Analysis | Virology and Bioinformatics from Virology.ca | Scoop.it

We present a new open source, extensible and flexible software platform for Bayesian evolutionary analysis called BEAST 2. This software platform is a re-design of the popular BEAST 1 platform to correct structural deficiencies that became evident as the BEAST 1 software evolved. Key among those deficiencies was the lack of post-deployment extensibility. BEAST 2 now has a fully developed package management system that allows third party developers to write additional functionality that can be directly installed to the BEAST 2 analysis platform via a package manager without requiring a new software release of the platform. This package architecture is showcased with a number of recently published new models encompassing birth-death-sampling tree priors, phylodynamics and model averaging for substitution models and site partitioning. A second major improvement is the ability to read/write the entire state of the MCMC chain to/from disk allowing it to be easily shared between multiple instances of the BEAST software. This facilitates checkpointing and better support for multi-processor and high-end computing extensions. Finally, the functionality in new packages can be easily added to the user interface (BEAUti 2) by a simple XML template-based mechanism because BEAST 2 has been re-designed to provide greater integration between the analysis engine and the user interface so that, for example BEAST and BEAUti use exactly the same XML file format.

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Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus: Cell

Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus: Cell | Virology and Bioinformatics from Virology.ca | Scoop.it

Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3-linked to α2,6-linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.

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Leading virologists join together to address urgent viral threat

Causing victims to suffer severe fever and pain, chikungunya virus has reached the Caribbean and South America – and is predicted to soon cause outbreaks in the United States. For many years the virus has remained primarily in Africa, the Indian subcontinent and Southeast Asia. In response to the arrival of the virus in the Western Hemisphere, the Global Virus Network (GVN) announced today the formation of the GVN Chikungunya Task Force, comprised of top virologists from around the world.

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Scientists Generate 3D Structure for the Malaria Parasite Genome

Scientists Generate 3D Structure for the Malaria Parasite Genome | Virology and Bioinformatics from Virology.ca | Scoop.it

Abstract - "A research team led by a cell biologist at the University of California, Riverside has generated a 3D model of the human malaria parasite genome at three different stages in the parasite’s life cycle — the first time such 3D architecture has been generated during the progression of the life cycle of a parasite ."

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Activation of the Interferon Induction Cascade by Influenza A Viruses Requires Viral RNA Synthesis and Nuclear Export


Via Mel Melendrez-Vallard, Ken Yaw Agyeman-Badu
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Decoding the massive genome of loblolly pine using haploid DNA and novel assembly strategies

The size and complexity of conifer genomes has, until now, prevented full genome sequencing and assembly. The large research community and economic importance of loblolly pine, Pinus taeda L., made it an early candidate for reference sequence determination.

We develop a novel strategy to sequence the genome of loblolly pine that combines unique aspects of pine reproductive biology and genome assembly methodology. We use a whole genome shotgun approach relying primarily on next generation sequence generated from a single haploid seed megagametophyte from a loblolly pine tree, 20-1010, that has been used in industrial forest tree breeding. The resulting sequence and assembly was used to generate a draft genome spanning 23.2 Gbp and containing 20.1 Gbp with an N50 scaffold size of 66.9 kbp, making it a significant improvement over available conifer genomes. The long scaffold lengths allow the annotation of 50,172 gene models with intron lengths averaging over 2.7 kbp and sometimes exceeding 100 kbp in length. Analysis of orthologous gene sets identifies gene families that may be unique to conifers. We further characterize and expand the existing repeat library based on thede novo analysis of the repetitive content, estimated to encompass 82% of the genome.

In addition to its value as a resource for researchers and breeders, the loblolly pine genome sequence and assembly reported here demonstrates a novel approach to sequencing the large and complex genomes of this important group of plants that can now be widely applied.


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IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion - PLoS Pathog. 2014

Influenza viruses are major human pathogens responsible for respiratory diseases affecting millions of people worldwide and characterized by high morbidity and significant mortality. Influenza infections can be controlled by vaccination and antiviral drugs. However, vaccines need annual updating and give limited protection. Only two classes of drugs are currently approved for the treatment of influenza: M2 ion channel blockers and neuraminidase inhibitors. However, they are often associated with limited efficacy and adverse side effects. In addition, the currently available drugs suffer from rapid and extensive emergence of drug resistance. All this highlights the urgent need for developing new antiviral strategies with novel mechanisms of action and with reduced drug resistance potential. Several new classes of antiviral agents targeting viral replication mechanisms or cellular proteins/processes are under development. This review gives an overview of novel strategies targeting the virus and/or the host cell for counteracting influenza virus infection.

A

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The 2010 Cholera Outbreak in Haiti: How Science Solved a Controversy

The 2010 Cholera Outbreak in Haiti: How Science Solved a Controversy | Virology and Bioinformatics from Virology.ca | Scoop.it

On January 12, 2010, a catastrophic 7.0 magnitude earthquake struck Haiti, affecting 3,500,000 people [1], [2]. This severely damaged an already marginal public sanitation system, creating ideal conditions for outbreaks of major infectious diseases. In October 2010, nine months after the earthquake, an outbreak of cholera started, which quickly spread all across the country [3]. As of January 7, 2014, 8,534 deaths and 697,256 cholera cases have been reported by the Haitian Ministry of Public Health and Population [4]. Prior to 2010, there was no reported history of cholera in Haiti, despite devastating outbreaks in the Caribbean region in the 19th century [5]. Many wondered where the cholera in Haiti came from. Two hypotheses as to its origin were presented. The climatic hypothesis argued that nonpathogenic Vibrio cholerae, indigenous in the coastal waters of Haiti, was given the right environmental circumstances and evolved into a pathogenic strain [6]. On the other hand, the human transmission hypothesis suggested that cholera was introduced to Haiti by individuals infected in a foreign country.

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If You Can't Measure It, You Can't Manage It

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