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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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New Treatment for Melanoma Uses a Form of the Herpes Virus

New Treatment for Melanoma Uses a Form of the Herpes Virus | Virology and Bioinformatics from Virology.ca | Scoop.it

The American Cancer Society estimates that about 74,000 Americans will be diagnosed with melanoma this year and almost 10,000 will die from this deadliest form of skin cancer. Over the past several years, treatment of advanced cases of melanoma has been transformed as new FDA-approved therapies developed by several different companies have come onto the market. An FDA advisory committee recently approved a therapy that takes a totally novel approach that involves injecting a live attenuated virus directly into regionally or distant metastatic melanoma tumors.

 

HSV-1 infections cause cold sores and sometimes genital herpes, although infection with human simplex virus 2 is more often the cause of genital herpes. Researchers have characterized the virulence genes of the virus. Talimogene laherparepvec, sometimes shortened to T-VEC, is made by depleting those virulence genes and inserting sequences that generate GM-CSF. It’s believed that removal of the virulence genes decreases the chances that the virus will infect nerve cells and will instead home in on tumor cells. By delivering GM-CSF, the genetically engineered virus enhances tumor antigen presentation to the immune system and induction of immune system attack on the malignancy.

Encouraging durable response results


Talimogene laherparepvec was studied in a randomized, open label phase 3 study to compare the new therapy with GM-CSF injections in subjects with unresectable stage IIIB, IIIC, and IV melanoma. A total of 437 subjects were randomized into the study at 64 study sites. The study was designed to demonstrate an improvement in durable response rate, which was defined as a complete response or partial response maintained for at least six months. Subjects were to receive therapy until Week 24, even if their melanoma was progressing. GM-CSF was used for comparison purposes because at the time that this study was designed, it was also in clinical studies as a treatment for melanoma. It is unclear, though, if GM-CSF by itself has any therapeutic value.


To be enrolled in the study, people had to be age 18 or older, have a histologically confirmed malignant melanoma of the stages listed in the previous paragraph, measurable disease of at least 1 cm, injectable disease (either on the surface of the skin or through the use of ultrasound guidance), ECOG performance of 0 or 1, and a life expectancy greater than four months from date of randomization. The study exclusions included active cerebral disease, any bone metastases, history of secondary cancer unless disease-free for at least five years, open herpetic skin lesions, and primary ocular or mucosal melanoma.


Via Krishan Maggon , Dr. Stefan Gruenwald
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U of T stands by health-studies course with anti-vaccine material

The University of Toronto says it stands by a health-studies course in which students were required to read and watch material stating vaccines are toxic and linked to serious health problems.

Chris Upton + helpers's insight:

UofT going down hill...   here's more evidence

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Scientists reveal structure of vesicular stomatitis virus protein

Scientists reveal structure of vesicular stomatitis virus protein | Virology and Bioinformatics from Virology.ca | Scoop.it
Viruses need us. In order to multiply, viruses have to invade a host cell and copy their genetic information. To do so, viruses encode their own replication machinery or components that subvert the host replication machinery to their advantage.

Ebola virus and rabies virus, two of the most lethal pathogens known to humans, belong to an order of RNA viruses that share a common strategy for copying their genomes inside their hosts. Other relatives include Marburg virus, measles, mumps, respiratory syncytial virus and vesicular stomatitis virus (VSV). Scientists study VSV, which causes acute disease in livestock but typically does not lead to illness in people, as a model for viruses that are harmful to humans.

Now a team from Harvard Medical School, using electron cryomicroscopy (imaging frozen specimens to reduce damage from electron radiation), has for the first time revealed the structure of a VSV protein at the atomic level. Called polymerase protein L, it is required for viral replication in this group of RNA viruses. The findings are published in Cell.

"We now have a better understanding of how RNA synthesis works for these viruses," said Sean Whelan, HMS professor of microbiology and immunobiology and senior author of the paper. "I think if you were trying to develop a viral-specific target to block the replication of one of these viruses, having the structure of the polymerase protein would help."

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Developing disease-resistant poultry may be solution for multiple virus issues

Developing disease-resistant poultry may be solution for multiple virus issues | Virology and Bioinformatics from Virology.ca | Scoop.it
Poultry disease is an international issue, especially when there is an outbreak close to home. However, it's a particularly costly problem in developing countries.


Developing animals resistant to disease may be one of the long-term solutions. University of Georgia researchers in the Regenerative Bioscience Center have spent the last four years gathering data that could make the process a reality.
The team, which includes Steven Stice and Franklin West in the College of Agricultural and Environmental Sciences and Claudio Afonso at the Southeast Poultry Research Laboratory of the U.S. Department of Agriculture's Agricultural Research Service, used a technology platform called shRNA—single strands of RNA that fold back on themselves—to selectively stop the production of nucleic acids that cause disease, such as the Newcastle disease virus.
Ed Rybicki's insight:

Genetically engineering livestock!!  It's going to happen, people: if we want to eat them, then why shouldn't we engineer tham?

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Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers

There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)–specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo–electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 “locks” two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.

Ed Rybicki's insight:

Sigh...it's ALWAYS going to help make vaccines, or be a major breakthrough, or enable therapy.  Be nice if it does, but I'm not holding my breath.

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Alteration of Protein Levels during Influenza Virus H1N1 Infection in Host Cells: A Proteomic Survey of Host and Virus Reveals Differential Dynamics

Alteration of Protein Levels during Influenza Virus H1N1 Infection in Host Cells: A Proteomic Survey of Host and Virus Reveals Differential Dynamics | Virology and Bioinformatics from Virology.ca | Scoop.it
We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1) infected Madin-Darby canine kidney cells up to 12 hours post infection by mass spectrometry based quantitative proteomics using the approach of stable isotope labeling by amino acids in cell culture (SILAC). We identified 1311 cell proteins and, apart from the proton channel M2, all major virus proteins. Based on their abundance two groups of virus proteins could be distinguished being in line with the function of the proteins in genesis and formation of new virions. Further, the data indicate a correlation between the amount of proteins synthesized and their previously determined copy number inside the viral particle. We employed bioinformatic approaches such as functional clustering, gene ontology, and pathway (KEGG) enrichment tests to uncover co-regulated cellular protein sets, assigned the individual subsets to their biological function, and determined their interrelation within the progression of viral infection. For the first time we are able to describe dynamic changes of the cellular and, of note, the viral proteome in a time dependent manner simultaneously. Through cluster analysis, time dependent patterns of protein abundances revealed highly dynamic up- and/or down-regulation processes. Taken together our study provides strong evidence that virus infection has a major impact on the cell status at the protein level.
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Evolutionary non-linear modelling for selecting vaccines against antigenically variable viruses

Evolutionary non-linear modelling for selecting vaccines against antigenically variable viruses | Virology and Bioinformatics from Virology.ca | Scoop.it
Motivation: In vitro and in vivo selection of vaccines is time consuming, expensive and the selected vaccines may not be able to provide protection against broad-spectrum viruses because of emerging antigenically novel disease strains. A powerful computational model that incorporates these protein/DNA or RNA level fluctuations can effectively predict antigenically variant strains, and can minimize the amount of resources spent on exclusive serological testing of vaccines and make wide spectrum vaccines possible for many diseases. However, in silico vaccine prediction remains a grand challenge. To address the challenge, we investigate the use of linear and non-linear regression models to predict the antigenic similarity in foot-and-mouth disease virus strains and in influenza strains, where the structure and parameters of the non-linear model are optimized using an evolutionary algorithm (EA). In addition, we examine two different scoring methods for weighting the type of amino acid substitutions in the linear and non-linear models. We also test our models with some unseen data.

Results: We achieved the best prediction results on three datasets of SAT2 (Foot-and-Mouth disease), two datasets of serotype A (Foot-and-Mouth disease) and two datasets of influenza when the scoring method based on biochemical properties of amino acids is employed in combination with a non-linear regression model. Models based on substitutions in the antigenic areas performed better than those that took the entire exposed viral capsid proteins. A majority of the non-linear regression models optimized with the EA performed better than the linear and non-linear models whose parameters are estimated using the least-squares method. In addition, for the best models, optimized non-linear regression models consist of more terms than their linear counterparts, implying a non-linear nature of influences of amino acid substitutions. Our models were also tested on five recently generated FMDV datasets and the best model was able to achieve an 80% agreement rate.
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ViRBase: a resource for virus–host ncRNA-associated interactions

ViRBase: a resource for virus–host ncRNA-associated interactions | Virology and Bioinformatics from Virology.ca | Scoop.it

Increasing evidence reveals that diverse non-coding RNAs (ncRNAs) play critically important roles in viral infection. Viruses can use diverse ncRNAs to manipulate both cellular and viral gene expression to establish a host environment conducive to the completion of the viral life cycle. Many host cellular ncRNAs can also directly or indirectly influence viral replication and even target virus genomes. ViRBase (http://www.rna-society.org/virbase) aims to provide the scientific community with a resource for efficient browsing and visualization of virus-host ncRNA-associated interactions and interaction networks in viral infection. The current version of ViRBase documents more than 12 000 viral and cellular ncRNA-associated virus–virus, virus–host, host–virus and host–host interactions involving more than 460 non-redundant ncRNAs and 4400 protein-coding genes from between more than 60 viruses and 20 hosts. Users can query, browse and manipulate these virus–host ncRNA-associated interactions. ViRBase will be of help in uncovering the generic organizing principles of cellular virus–host ncRNA-associated interaction networks in viral infection.

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New Metrics for Evaluating Viral Respiratory Pathogenesis

New Metrics for Evaluating Viral Respiratory Pathogenesis | Virology and Bioinformatics from Virology.ca | Scoop.it
Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-ter
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Detection of significant protein coevolution

Motivation: The evolution of proteins cannot be fully understood without taking into account the coevolutionary linkages entangling them. From a practical point of view, coevolution between protein families has been used as a way of detecting protein interactions and functional relationships from genomic information. The most common approach to inferring protein coevolution involves the quantification of phylogenetic tree similarity using a family of methodologies termed mirrortree. In spite of their success, a fundamental problem of these approaches is the lack of an adequate statistical framework to assess the significance of a given coevolutionary score (tree similarity). As a consequence, a number of ad hoc filters and arbitrary thresholds are required in an attempt to obtain a final set of confident coevolutionary signals.

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EpiToolKit—a web-based workbench for vaccine design

EpiToolKit is a virtual workbench for immunological questions with a focus on vaccine design. It offers an array of immunoinformatics tools covering MHC genotyping, epitope and neo-epitope prediction, epitope selection for vaccine design, and epitope assembly. In its recently re-implemented version 2.0, EpiToolKit provides a range of new functionality and for the first time allows combining tools into complex workflows. For inexperienced users it offers simplified interfaces to guide the users through the analysis of complex immunological data sets.

 
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Genome researchers raise alarm over big data

Storing and processing genome data will exceed the computing challenges of running YouTube and Twitter, biologists warn.
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Dengue Fever Virus is Rapidly Evolving

Dengue Fever Virus is Rapidly Evolving | Virology and Bioinformatics from Virology.ca | Scoop.it

Scientists have been looking at dengue fever and they have concluded that the virus that causes the disease is capable of rapid evolution. This means finding ways to kill the virus is a very challenging task.

 

Dengue virus is prevalent in some 100 countries worldwide and the signs are that the disease is spreading to more territories. By spreading the genetic diversity of the virus has increased, meaning that the hunt for effective counter drugs becomes more difficult.


Dengue fever is a disease, spread by mosquitoes, that affects over 50 million people a year. The disease manifests as fever, headache, muscle and joint pains, accompanied by a skin rash. In some cases fatal dengue hemorrhagic fever can result, causing internal bleeding.


A researcher at Duke-NUS called Eng Eong Ooi has recently found a new strain of dengue, called serotype 2 virus (DENV-2). This stain has evolved from and replaced another form of the virus that was common during the 1990s, in Puerto Rico. The dengue virus has four known serotypes (DENV1-4) circulating in nature.


The virus was able to make this genetic transformation due to three mutations that have been discovered in the tail of the dengue viral genome. Through these mutations the viral strain was able to suppress the human antiviral response. This allowed the newly emerging strain to spread, infect more mosquitoes and thus infect more people.


The study is important because it provides a new understanding as to how the virus mutates and this insight might offer ways to combat the virus. Studying the virus at the genetic level also provides information about which stains of the virus are most likely to trigger epidemics. This information is useful in dengue surveillance.


The research has been published in the journal Science (“Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness.”)


Via Dr. Stefan Gruenwald
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Identification of Ebola virus microRNAs and their putative pathological function - Springer

Identification of Ebola virus microRNAs and their putative pathological function - Springer | Virology and Bioinformatics from Virology.ca | Scoop.it

Ebola virus (EBOV), a member of the filovirus family, is an enveloped negative-sense RNA virus that causes lethal infections in humans and primates. Recently, more than 1000 people have been killed by the Ebola virus disease in Africa, yet no specific treatment or diagnostic tests for EBOV are available. In this study, we identified two putative viral microRNA precursors (pre-miRNAs) and three putative mature microRNAs (miRNAs) derived from the EBOV genome. The production of the EBOV miRNAs was further validated in HEK293T cells transfected with a pcDNA6.2-GW/EmGFP-EBOV-pre-miRNA plasmid, indicating that EBOV miRNAs can be produced through the cellular miRNA processing machinery. We also predicted the potential target genes of these EBOV miRNAs and their possible biological functions. Overall, this study reports for the first time that EBOV may produce miRNAs, which could serve as non-invasive biomarkers for the diagnosis and prognosis of EBOV infection and as therapeutic targets for Ebola viral infection treatment.

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Human antibody blocks dengue virus in mice - EurekAlert (press release)

Human antibody blocks dengue virus in mice - EurekAlert (press release) | Virology and Bioinformatics from Virology.ca | Scoop.it
Researchers have discovered that a human antibody specific to dengue virus serotype 2, called 2D22, protects mice from a lethal form of the virus -- and they suggest that the site where 2D22 binds to the virus could represent a potential vaccine...

Via Gilbert Faure au nom de l'ASSIM
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New Virus, Not EV-D68, Now Suspected in Childhood Paralysis

New Virus, Not EV-D68, Now Suspected in Childhood Paralysis | Virology and Bioinformatics from Virology.ca | Scoop.it
A novel virus from Peru and the Republic of Congo called enterovirus C105 is now suspected in last year's wave of mysterious cases of sudden childhood paralysis.
Ed Rybicki's insight:

It has always been my fear that PCR-based diagnostics only detect that which we know, or what is like what we know - and not what we don't.  And here all it took was a divergence in a supposedly conserved genomic region commonly used for PCR, for a virus not to be detected.  Broader spectrum detection needed, people!

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PLOS Computational Biology: Ten Years of PLoS‡ Computational Biology: A Decade of Appreciation and Innovation

PLOS Computational Biology: Ten Years of PLoS‡ Computational Biology: A Decade of Appreciation and Innovation | Virology and Bioinformatics from Virology.ca | Scoop.it
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VirHostNet 2.0: surfing on the web of virus/host molecular interactions data

VirHostNet 2.0: surfing on the web of virus/host molecular interactions data | Virology and Bioinformatics from Virology.ca | Scoop.it

VirHostNet release 2.0 (http://virhostnet.prabi.fr) is a knowledgebase dedicated to the network-based exploration of virus–host protein–protein interactions. Since the previous VirhostNet release (2009), a second run of manual curation was performed to annotate the new torrent of high-throughput protein–protein interactions data from the literature. This resource is shared publicly, in PSI-MI TAB 2.5 format, using a PSICQUIC web service. The new interface of VirHostNet 2.0 is based on Cytoscape web library and provides a user-friendly access to the most complete and accurate resource of virus–virus and virus–host protein–protein interactions as well as their projection onto their corresponding host cell protein interaction networks. We hope that the VirHostNet 2.0 system will facilitate systems biology and gene-centered analysis of infectious diseases and will help to identify new molecular targets for antiviral drugs design. This resource will also continue to help worldwide scientists to improve our knowledge on molecular mechanisms involved in the antiviral response mediated by the cell and in the viral strategies selected by viruses to hijack the host immune system.

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BMC Bioinformatics | Full text | TMFoldRec: a statistical potential-based transmembrane protein fold recognition tool

Transmembrane proteins (TMPs) are the key components of signal transduction, cell-cell adhesion and energy and material transport into and out from the cells. For the deep understanding of these processes, structure determination of transmembrane proteins is indispensable. However, due to technical difficulties, only a few transmembrane protein structures have been determined experimentally. Large-scale genomic sequencing provides increasing amounts of sequence information on the proteins and whole proteomes of living organisms resulting in the challenge of bioinformatics; how the structural information should be gained from a sequence.
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Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza

Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza | Virology and Bioinformatics from Virology.ca | Scoop.it
The human immune response to influenza vaccination depends in part on preexisting cross-reactive (heterosubtypic) immunity from previous infection by, and/or vaccination with, influenza strains that share antigenic determinants with the vaccine strains. However, current methods for assessing heterosubtypic antibody responses against influenza, including the hemagglutination-inhibition (HAI) assay and ELISA, are time and labor intensive, and require moderate amounts of serum and reagents. To add
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Unified representation of genetic variants

Summary: A genetic variant can be represented in the Variant Call Format (VCF) in multiple different ways. Inconsistent representation of variants between variant callers and analyses will magnify discrepancies between them and complicate variant filtering and duplicate removal. We present a software tool vt normalize that normalizes representation of genetic variants in the VCF. We formally define variant normalization as the consistent representation of genetic variants in an unambiguous and concise way and derive a simple general algorithm to enforce it. We demonstrate the inconsistent representation of variants across existing sequence analysis tools and show that our tool facilitates integration of diverse variant types and call sets.

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Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence

Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence | Virology and Bioinformatics from Virology.ca | Scoop.it
Author Summary Human influenza virus commonly causes disease in the winter months of temperate countries, but exhibits more complex patterns in tropical localities. Most studies of this complex seasonality have only considered viruses sampled within the “normal” influenza season. To help reveal the drivers of influenza seasonality we utilized viruses sampled outside of the normal influenza season, focusing on Australia which is characterized by a wide range of climates. Using a phylogenetic a
Ed Rybicki's insight:

Nice piece of work: helps reinforce the notion that influenza doesn't actually go away, especially in tropical and subtropical areas!

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