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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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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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Friendly Viruses Protect Us Against Bacteria

Friendly Viruses Protect Us Against Bacteria | Virology and Bioinformatics from Virology.ca | Scoop.it
Viruses in mucus may be important line of defense against disease
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Mutational and fitness landscapes of an RNA virus revealed through population sequencing : Nature

Mutational and fitness landscapes of an RNA virus revealed through population sequencing : Nature | Virology and Bioinformatics from Virology.ca | Scoop.it
RNA viruses exist as genetically diverse populations. It is thought that diversity and genetic structure of viral populations determine the rapid adaptation observed in RNA viruses and hence their pathogenesis. However, our understanding of the mechanisms underlying virus evolution has been limited by the inability to accurately describe the genetic structure of virus populations. Next-generation sequencing technologies generate data of sufficient depth to characterize virus populations, but are limited in their utility because most variants are present at very low frequencies and are thus indistinguishable from next-generation sequencing errors. Here we present an approach that reduces next-generation sequencing errors and allows the description of virus populations with unprecedented accuracy. Using this approach, we define the mutation rates of poliovirus and uncover the mutation landscape of the population. Furthermore, by monitoring changes in variant frequencies on serially passaged populations, we determined fitness values for thousands of mutations across the viral genome. Mapping of these fitness values onto three-dimensional structures of viral proteins offers a powerful approach for exploring structure-function relationships and potentially uncovering new functions. To our knowledge, our study provides the first single-nucleotide fitness landscape of an evolving RNA virus and establishes a general experimental platform for studying the genetic changes underlying the evolution of virus populations.
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A novel codon-optimized SIV gag-pol immunogen for gene-based vaccination

A novel codon-optimized SIV gag-pol immunogen for gene-based vaccination | Virology and Bioinformatics from Virology.ca | Scoop.it

Simian immunodeficiency virus (SIV) is a robust pathogen used in non-human primates to model HIV vaccines. SIV encodes a number of potential vaccine targets. By far the largest and most conserved protein target in SIV is gag-pol encodes many epitopes with potential to drive multivalent T cell responses. While it is an attractive antigen, pol is only translated after a frame shift from gag so that only 1 in 10 gag proteins include this larger antigen. The codon bias of native lentiviral genes are also mismatched with the abundance of tRNAs in mammalian cells resulting in poor expression of unmodified SIV genes. To provide a better SIV gag-pol immunogen for gene-based vaccination, we codon-optimized the full gag-pol sequence from SIVmac239. To increase pol expression, we artificially moved the pol sequence in frame to gag to bypass the need for a translational frame shift for its expression. Finally, we inserted four “self-cleaving” picornavirus sequences into gag p24, protease, reverse transcriptase, and into integrase to fragment the proteins for potentially better immune presentation. We demonstrate that these immunogens are well expressed in vitro and drive similar antibody and T cell responses with or without cleavage sequences.

  
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Adaptive Evolution and Environmental Durability Jointly Structure Phylodynamic Patterns in Avian Influenza Viruses

Adaptive Evolution and Environmental Durability Jointly Structure Phylodynamic Patterns in Avian Influenza Viruses | Virology and Bioinformatics from Virology.ca | Scoop.it
Avian influenza viruses (AIVs) have been pivotal to the origination of human pandemic strains. Despite their scientific and public health significance, however, there remains much to be understood about the ecology and evolution of AIVs in wild birds, where major pools of genetic diversity are generated and maintained. Here, we present comparative phylodynamic analyses of human and AIVs in North America, demonstrating (i) significantly higher standing genetic diversity and (ii) phylogenetic trees with a weaker signature of immune escape in AIVs than in human viruses. To explain these differences, we performed statistical analyses to quantify the relative contribution of several potential explanations. We found that HA genetic diversity in avian viruses is determined by a combination of factors, predominantly subtype-specific differences in host immune selective pressure and the ecology of transmission (in particular, the durability of subtypes in aquatic environments). Extending this analysis using a computational model demonstrated that virus durability may lead to long-term, indirect chains of transmission that, when coupled with a short host lifespan, can generate and maintain the observed high levels of genetic diversity. Further evidence in support of this novel finding was found by demonstrating an association between subtype-specific environmental durability and predicted phylogenetic signatures: genetic diversity, variation in phylogenetic tree branch lengths, and tree height. The conclusion that environmental transmission plays an important role in the evolutionary biology of avian influenza viruses—a manifestation of the “storage effect”—highlights the potentially unpredictable impact of wildlife reservoirs for future human pandemics and the need for improved understanding of the natural ecology of these viruses.
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Data sharing: Make outbreak research open access

Data sharing: Make outbreak research open access | Virology and Bioinformatics from Virology.ca | Scoop.it
Establish principles for rapid and responsible data sharing in epidemics, urge Nathan L. Yozwiak, Stephen F. Schaffner and Pardis C. Sabeti.
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I wasn't always a scientist | Royal Society

Series of films about scientists who didn’t take traditional routes into their scientific careers.
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Researchers Use Polio Virus for Cancer Treatment

Researchers Use Polio Virus for Cancer Treatment | Virology and Bioinformatics from Virology.ca | Scoop.it
The cure to cancer could come from researchers at the Duke University Hospital Cancer Center.

 

Duke Medicine’s Dr. Matthias Gromeier has been working on a Glioblastoma treatment using a modified polio virus for more than 25-years.

Now, Duke researchers are testing the treatment and trials show it is working for some patients. 

After doctors told Clara Guy she had six to 18-months to live, she transferred to Duke Medicine’s Preston Robert Tisch Brain Tumor Center, where she became a stage four Glioblastoma research patient.  Glioblastoma is an aggressive and fast growing type of brain cancer.

"It's a big word...Glioblastoma is so much than a four letter word, and it really ought to be,” she said.

Guy was under the regulate vaccine trial.

"It turns your immune system onto high gear to teach it to fight the cancer cells,” she said. 

Neurooncologist Dr. Annick Desjardins is using the genetically modified polio virus as treatment for some patients during Phase One of the research. 


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How should journalists cover quacks like Dr. Oz or the Food Babe?

The media has always had a hard time dealing with popular peddlers of pseudoscience.
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Learning the Hard Way: My Journey from #AntiVaxx to Science

Learning the Hard Way: My Journey from #AntiVaxx to Science | Virology and Bioinformatics from Virology.ca | Scoop.it
Written by Tara Hills I’m writing this from quarantine, the irony of which isn’t lost on me. Emotionally I’m a bit raw. Mentally a bit taxed. Physically I’m fine.  All seven of my unvaccinated chil...
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Markov Chain Monte Carlo Without all the Bullshit

Markov Chain Monte Carlo Without all the Bullshit | Virology and Bioinformatics from Virology.ca | Scoop.it
I have a little secret: I don't like the terminology, notation, and style of writing in statistics. I find it unnecessarily complicated. This shows up when trying to read about Markov Chain Monte C...
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A Virus In Your Mouth Helps Fight The Flu

A Virus In Your Mouth Helps Fight The Flu | Virology and Bioinformatics from Virology.ca | Scoop.it
It's related to herpes. And it infects most of the world — about half of Americans, nearly all the developing world. But don't go out and get infected. The virus has a dark side, too.
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Replicating poxviruses for human cancer therapy. - PubMed - NCBI

Replicating poxviruses for human cancer therapy. - PubMed - NCBI | Virology and Bioinformatics from Virology.ca | Scoop.it

Naturally occurring oncolytic viruses are live, replication-proficient viruses that specifically infect human cancer cells while sparing normal cell counterparts. Since the eradication of smallpox in the 1970s with the aid of vaccinia viruses, the vaccinia viruses and other genera of poxviruses have shown various degrees of safety and efficacy in pre-clinical or clinical application for human anti-cancer therapeutics. Furthermore, we have recently discovered that cellular tumor suppressor genes are important in determining poxviral oncolytic tropism. Since carcinogenesis is a multi-step process involving accumulation of both oncogene and tumor suppressor gene abnormalities, it is interesting that poxvirus can exploit abnormal cellular tumor suppressor signaling for its oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ATM, and RB are known to play important roles in genomic fidelity/maintenance. Thus, tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to accumulation of genetic defects, which would in turn result in oncolytic virus susceptibility. This review outlines the characteristics of oncolytic poxvirus strains, including vaccinia, myxoma, and squirrelpox virus, recent progress in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and poxviral oncolytic tropism, and the associated preclinical/clinical implications. I would also like to propose future directions in the utility of poxviruses for oncolytic virotherapy.

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To prevent the next Ebola, scientists try to catch new viruses before they break out

To prevent the next Ebola, scientists try to catch new viruses before they break out | Virology and Bioinformatics from Virology.ca | Scoop.it
With the Ebola outbreak not yet behind us, global health workers are already scrambling to prevent what could be the next big outbreak of an emerging disease caused by a virus that jumped from animals into humans. In Tanzania, an organization is trying a new approach to tracking these new viruses and preventing another pandemic. #
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Near-atomic cryo-EM structure of the helical measles virus nucleocapsid - Science

Measles is a highly contagious human disease. We used cryo-electron microscopy and single particle-based helical image analysis to determine the 4.3 Å resolution structure of the helical nucleocapsid formed by the folded domain of the Measles Virus nucleoprotein encapsidating an RNA. The resulting pseudoatomic model of the Measles Virus nucleocapsid offers important insights into the mechanism of the helical polymerisation of nucleocapsids of negative-strand RNA viruses, in particular via the exchange subdomains of the nucleoprotein.The structure reveals the mode of the nucleoprotein-RNA interaction and explains why each nucleoprotein of Measles Virus binds six nucleotides whereas the Respiratory Syncytial Virus nucleoprotein binds seven. It provides a rational basis for further analysis of Measles Virus replication and transcription, and reveals potential targets for drug design.
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Ebolavirus is evolving but not changing: No evidence for functional change in EBOV from 1976 to the 2014 outbreak. - PubMed - NCBI

The 2014 epidemic of Ebola virus disease (EVD) has had a devastating impact in West Africa. Sequencing of ebolavirus (EBOV) from infected individuals has revealed extensive genetic variation, leading to speculation that the virus may be adapting to humans, accounting for the scale of the 2014 outbreak. We computationally analyze the variation associated with all EVD outbreaks, and find none of the amino acid replacements lead to identifiable functional changes. These changes have minimal effect on protein structure, being neither stabilizing nor destabilizing, are not found in regions of the proteins associated with known functions and tend to cluster in poorly constrained regions of proteins, specifically intrinsically disordered regions. We find no evidence that the difference between the current and previous outbreaks is due to evolutionary changes associated with transmission to humans. Instead, epidemiological factors are likely to be responsible for the unprecedented spread of EVD.

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A review on computational systems biology of pathogen–host interactions | Frontiers | Infectious Diseases

Pathogens manipulate the cellular mechanisms of host organisms via pathogen–host interactions (PHIs) in order to take advantage of the capabilities of host cells, leading to infections. The crucial role of these interspecies molecular interactions in initiating and sustaining infections necessitates a thorough understanding of the corresponding mechanisms. Unlike the traditional approach of considering the host or pathogen separately, a systems-level approach, considering the PHI system as a whole is indispensable to elucidate the mechanisms of infection. Following the technological advances in the post-genomic era, PHI data have been produced in large-scale within the last decade. Systems biology-based methods for the inference and analysis of PHI regulatory, metabolic, and protein–protein networks to shed light on infection mechanisms are gaining increasing demand thanks to the availability of omics data. The knowledge derived from the PHIs may largely contribute to the identification of new and more efficient therapeutics to prevent or cure infections. There are recent efforts for the detailed documentation of these experimentally verified PHI data through Web-based databases. Despite these advances in data archiving, there are still large amounts of PHI data in the biomedical literature yet to be discovered, and novel text mining methods are in development to unearth such hidden data. Here, we review a collection of recent studies on computational systems biology of PHIs with a special focus on the methods for the inference and analysis of PHI networks, covering also the Web-based databases and text-mining efforts to unravel the data hidden in the literature
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SNPer: An R Library for Quantitative Variant Analysis on Single Nucleotide Polymorphisms among Influenza Virus Populations. - PLoS One

Influenza virus (IFV) can evolve rapidly leading to genetic drifts and shifts resulting in human and animal influenza epidemics and pandemics. The genetic shift that gave rise to the 2009 influenza A/H1N1 pandemic originated from a triple gene reassortment of avian, swine and human IFVs. More minor genetic alterations in genetic drift can lead to influenza drug resistance such as the H274Y mutation associated with oseltamivir resistance. Hence, a rapid tool to detect IFV mutations and the potential emergence of new virulent strains can better prepare us for seasonal influenza outbreaks as well as potential pandemics. Furthermore, identification of specific mutations by closely examining single nucleotide polymorphisms (SNPs) in IFV sequences is essential to classify potential genetic markers associated with potentially dangerous IFV phenotypes. In this study, we developed a novel R library called "SNPer" to analyze quantitative variants in SNPs among IFV subpopulations. The computational SNPer program was applied to three different subpopulations of published IFV genomic information. SNPer queried SNPs data and grouped the SNPs into (1) universal SNPs, (2) likely common SNPs, and (3) unique SNPs. SNPer outperformed manual visualization in terms of time and labor. SNPer took only three seconds with no errors in SNP comparison events compared with 40 hours with errors using manual visualization. The SNPer tool can accelerate the capacity to capture new and potentially dangerous IFV strains to mitigate future influenza outbreaks.

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Virology tidbits: Porcine Circovirus: Autophagy. Nucleolus, and Apoptosis

Virology tidbits: Porcine Circovirus: Autophagy. Nucleolus, and Apoptosis | Virology and Bioinformatics from Virology.ca | Scoop.it
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Cancer virology researchers reveal new pathway that controls how cells make proteins

Cancer virology researchers reveal new pathway that controls how cells make proteins | Virology and Bioinformatics from Virology.ca | Scoop.it
A serendipitous combination of technology and scientific discovery, coupled with a hunch, allowed University of Pittsburgh Cancer Institute (UPCI) researchers to reveal a previously invisible biological process that may be implicated in the rapid growth of some cancers.
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Genomics, Medicine, and Pseudoscience: How disruptive are MOOCs? Hopkins launches new genomic data science series.

Genomics, Medicine, and Pseudoscience: How disruptive are MOOCs? Hopkins launches new genomic data science series. | Virology and Bioinformatics from Virology.ca | Scoop.it
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GEN | Insight & Intelligence™:Targeting Kinases Essential to Malaria Parasites

GEN | Insight & Intelligence™:Targeting Kinases Essential to Malaria Parasites | Virology and Bioinformatics from Virology.ca | Scoop.it
A large unmet medical need exists for effective new treatments for malaria in the developing world.
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What Are Quadratic Equations?

What Are Quadratic Equations? | Virology and Bioinformatics from Virology.ca | Scoop.it
Quadratic equations are basic to algebra and are the math behind parabolas, projectiles, satellite dishes and the golden ratio.
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Mysterious Childhood Paralysis Linked to a Common Cold Virus

Mysterious Childhood Paralysis Linked to a Common Cold Virus | Virology and Bioinformatics from Virology.ca | Scoop.it

Scientists have found evidence that a polio-like virus called EV-D68 is behind a mysterious outbreak of paralysis in children [in the USA] last year.

 

LAST YEAR, HUNDREDS of children across the country got sick with what looked like a common cold. Nothing to worry about: body aches, runny nose, coughing and sneezing. But then, mysteriously, a handful of those kids became paralyzed—first, just in an arm or a leg, and then spreading so far that some children needed a ventilator to breathe. The CDC reports that since August 2014, at least 115 children in 34 states have developed unexplained muscle weakness or paralysis, which they’re now calling acute flaccid myelitis. Doctors have urgently been hunting down the origin of this strange illness for over half a year, and now they think they’ve finally identified the culprit: enterovirus D68.

 


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Ed Rybicki's curator insight, April 3, 7:46 AM

And it's going to spread...vaccine time, people!

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Virus Infects Winter Cereal Crops

Virus Infects Winter Cereal Crops | Virology and Bioinformatics from Virology.ca | Scoop.it
TWIN FALLS • A major disease threat to winter wheat and barley has appeared in fields across southern Idaho.

 

Barley yellow dwarf virus “is rampant from Parma to Ririe,” said Juliet Marshall, a University of Idaho Extension cereal pathologist in Idaho Falls. Some growers are killing infected fields and reseeding with other crops.

 


Via Ed Rybicki
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Ed Rybicki's curator insight, April 3, 7:42 AM

Ah, BYDV...back to my roots of 31 years ago, when I published a paper and a thesis on BYDV in SOuth African small grains.  It's never gone away.

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Video Tip of The Week: Jalview for multiple sequence alignment editing and visualization | The OpenHelix Blog

Video Tip of The Week: Jalview for multiple sequence alignment editing and visualization | The OpenHelix Blog | Virology and Bioinformatics from Virology.ca | Scoop.it
The multiple sequence alignment editing question recently on our What's the Answer? feature was popular. We have covered MSA editors in the past, and we include
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