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Genomic Variation in Seven Khoe-San Groups Reveals Adaptation and Complex African History

"The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ∼2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history."

 

Ex Africa, semper aliquid novi...or old, in this case!

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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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BMC Bioinformatics | Full text | ReformAlign: improved multiple sequence alignments using a profile-based meta-alignment approach

Obtaining an accurate sequence alignment is fundamental for consistently analyzing biological data. Although this problem may be efficiently solved when only two sequences are considered, the exact inference of the optimal alignment easily gets computationally intractable for the multiple sequence alignment case. To cope with the high computational expenses, approximate heuristic methods have been proposed that address the problem indirectly by progressively aligning the sequences in pairs according to their relatedness. These methods however are not flexible to change the alignment of an already aligned group of sequences in the view of new data, resulting thus in compromises on the quality of the deriving alignment. In this paper we present ReformAlign, a novel meta-alignment approach that may significantly improve on the quality of the deriving alignments from popular aligners. We call ReformAlign a meta-aligner as it requires an initial alignment, for which a variety of alignment programs can be used. The main idea behind ReformAlign is quite straightforward: at first, an existing alignment is used to construct a standard profile which summarizes the initial alignment and then all sequences are individually re-aligned against the formed profile. From each sequence-profile comparison, the alignment of each sequence against the profile is recorded and the final alignment is indirectly inferred by merging all the individual sub-alignments into a unified set. The employment of ReformAlign may often result in alignments which are significantly more accurate than the starting alignments.
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▶ Webinar: BLAST in the Cloud - YouTube

Presented July 30, 2014 and covering: an NCBI BLAST AMI at Amazon Web Services; introduction to AWS and setting up an instance; running command line BLAST an...
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Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses

Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses | Virology and Bioinformatics from Virology.ca | Scoop.it
Significance

Studies using novel “shotgun glycan microarray” technology identify, for the first time to our knowledge, the endogenous receptors for influenza viruses from a natural host, the pig. Libraries of total N-glycans from pig lung were probed for binding properties using a panel of influenza viruses isolated from humans, birds, and swine. Natural glycan receptors were identified for all viruses examined, and although some displayed the rather broad α2,3 or α2,6 sialic acid linkage specificity conventionally associated with avian or human viruses, other strains were highly specific, revealing a complexity that has not been demonstrated previously. Because pigs are often implicated as intermediate hosts for pandemic viruses, these results and the approaches described will transform our understanding of influenza host range, transmission, and pathogenicity.

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Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses

Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent clinical phenotype seen in human LAIV inoculation.

 

Ed Rybicki's insight:

Well, of course they do: they engage ALL the levers making the immune system work!

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Next-Gen Sequencing Is A Numbers Game | August 18, 2014 Issue - Vol. 92 Issue 33 | Chemical & Engineering News

Next-Gen Sequencing Is A Numbers Game | August 18, 2014 Issue - Vol. 92 Issue 33 | Chemical & Engineering News | Virology and Bioinformatics from Virology.ca | Scoop.it
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VDU's blog: Ebola Virus Disease (EVD) 2014 West African outbreak..

VDU's blog: Ebola Virus Disease (EVD) 2014 West African outbreak.. | Virology and Bioinformatics from Virology.ca | Scoop.it
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40 Greatest Rock Documentaries

40 Greatest Rock Documentaries | Virology and Bioinformatics from Virology.ca | Scoop.it
From meeting the Beatles to Hendrix burning guitars, here are the 40 greatest rock documentaries of all time.
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Just because...

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Ed Rybicki's curator insight, August 20, 10:16 PM

This is one of those "other things" that this site is for B-)

 

Of course, they fail badly by not including "Mad Dogs and Englishmen", but I suppose they got it mostly right.

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The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin - Elife. 2014

The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin - Elife. 2014 | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.

 

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How a Canadian Prairie city made an Ebola vaccine

How a Canadian Prairie city made an Ebola vaccine | Virology and Bioinformatics from Virology.ca | Scoop.it
An experimental Ebola vaccine that is offering some hope for West Africa was invented in a small Canadian Prairie city and had its roots in the Cold War, the German town of Marburg and a disease scare that panicked Toronto in the 1970s.
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Mutational tolerance helps influenza evade the immune system

Mutational tolerance helps influenza evade the immune system | Virology and Bioinformatics from Virology.ca | Scoop.it
The influenza protein hemagglutinin is highly tolerant of mutations in its antigenic sites, allowing rapid evolution to evade the immune system.
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How Viruses Hijack the ERAD Tuning Machinery

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An essential step during the intracellular life cycle of many positive-strand RNA viruses is the rearrangement of host cell membranes to generate membrane-bound replication platforms. For example, Nidovirales and Flaviviridae subvert the membrane of the endoplasmic reticulum (ER) for their replication. However, the absence of conventional ER and secretory pathway markers in virus-induced ER-derived membranes has for a long time hampered a thorough understanding of their biogenesis.

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Molecular Flipbook: easy way to make videos with structures

Molecular Flipbook: easy way to make videos with structures | Virology and Bioinformatics from Virology.ca | Scoop.it
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Coordinated Evolution of Influenza A Surface Proteins

Coordinated Evolution of Influenza A Surface Proteins | Virology and Bioinformatics from Virology.ca | Scoop.it

Surface proteins hemagglutinin (HA) and neuraminidase (NA) of the human influenza A virus evolve under selection pressure to escape the human adaptive immune response and antiviral drug treatments. In addition to these external selection pressures, some mutations in HA are known to affect the adaptive landscape of NA, and vice versa, because these two proteins are physiologically interlinked. However, the extent to which evolution of one protein affects the evolution of the other is unknown. Here we develop a novel phylogenetic method for detecting the signatures of such genetic interactions between mutations in different genes, that is, inter-gene epistasis. Using this method, we show that influenza surface proteins evolve in a coordinated way, with substitutions in HA affecting substitutions in NA and vice versa, at many sites. Of particular interest is our finding that the oseltamivir-resistance mutations in NA in subtype H1N1 were likely facilitated by prior mutations in HA. Our results illustrate that the adaptive landscape of a viral protein is remarkably sensitive to its genomic context and, more generally, imply that the evolution of any single protein must be understood within the context of the entire evolving genome.

 
Ed Rybicki's insight:

Cool stuff - and so is the fact that they used BioRxiv, the "Preprint Server for Biology".  Some day, most biological papers may be done like this...B-)

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The 3 Dumbest Things About Whole Foods Market

The 3 Dumbest Things About Whole Foods Market | Virology and Bioinformatics from Virology.ca | Scoop.it
Whole Foods Market sells wonderful fresh food, but they also sell homeopathic remedies and nutritional supplements, promoting them with little more than hand-waving claims about "immune support." For real medicine, go somewhere else.
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Progress in the Prevention and Treatment of RSV Infection — NEJM

At long last, gratifying progress is evident on many fronts in combating respiratory syncytial virus (RSV) infection. RSV was discovered in 1956 as an agent causing coryza in chimpanzees.1 Its clinical effects became evident shortly thereafter through a strong epidemiologic association of RSV infection with bronchiolitis and pneumonia in young infants.2 In the almost 60 years since the virus was identified, the highlights of RSV research have been relatively few, in spite of dedicated groups working in this field. The reasons for this include the difficulty of working with RSV in the laboratory; the confinement of RSV replication in humans . . .

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Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza A and B viruses cocirculate in humans and together cause disease and seasonal epidemics. These two types of influenza viruses are evolutionarily divergent, and exchange of genetic segments inside coinfected cells occurs frequently within types but never between influenza A and B viruses. Possible mechanisms inhibiting the intertypic reassortment of genetic segments could be due to incompatible protein functions of segment homologs, a lack of processing of heterotypic segments by influenza virus RNA-dependent RNA polymerase, an inhibitory effect of viral proteins on heterotypic virus function, or an inability to specifically incorporate heterotypic segments into budding virions. Here, we demonstrate that the full-length hemagglutinin (HA) of prototype influenza B viruses can complement the function of multiple influenza A viruses. We show that viral noncoding regions were sufficient to drive gene expression for either type A or B influenza virus with its cognate or heterotypic polymerase. The native influenza B virus HA segment could not be incorporated into influenza A virus virions. However, by adding the influenza A virus packaging signals to full-length influenza B virus glycoproteins, we rescued influenza A viruses that possessed HA, NA, or both HA and NA of influenza B virus. Furthermore, we show that, similar to single-cycle infectious influenza A virus, influenza B virus cannot incorporate heterotypic transgenes due to packaging signal incompatibilities. Altogether, these results demonstrate that the lack of influenza A and B virus reassortants can be attributed at least in part to incompatibilities in the virus-specific packaging signals required for effective segment incorporation into nascent virions.

 

Flu virus mixing graphic from Russell Kightley Media

 

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Ebola Protein Discovery Could Clear Path For Treatment - YouTube

Researchers found Ebola's VP24 protein interferes with the body's immune response system. It's a finding that could lead to future treatment. Follow Jay Stru...
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Microbiology: Microbiome science needs a healthy dose of scepticism

Microbiology: Microbiome science needs a healthy dose of scepticism | Virology and Bioinformatics from Virology.ca | Scoop.it
To guard against hype, those interpreting research on the body's microscopic communities should ask five questions, says William P. Hanage.
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Profile Hidden Markov Models for the Detection of Viruses within Metagenomic Sequence Data

Profile Hidden Markov Models for the Detection of Viruses within Metagenomic Sequence Data | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
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Volunteers help British Museum in crowdsourcing archeology project

Volunteers help British Museum in crowdsourcing archeology project | Virology and Bioinformatics from Virology.ca | Scoop.it
Thousands log on to transcribe handwritten catalogue dating back to 18th century and put 30,000 ancient objects online Continue reading...
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WikiWand Makes Wikipedia Beautiful

WikiWand Makes Wikipedia Beautiful | Virology and Bioinformatics from Virology.ca | Scoop.it
Wikipedia is one of the Web’s most visited properties. From quantum mechanics to Laurel and Hardy, the online encyclopedia delivers good primers on just about any topic you can think... Keep reading →
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5 Viruses That Are More Frightening Than Ebola

5 Viruses That Are More Frightening Than Ebola | Virology and Bioinformatics from Virology.ca | Scoop.it

By Elizabeth Palermo, Staff Writer
Published: 08/15/2014 01:58 PM EDT on LiveScience
The Ebola virus has now killed more than 1,000 people in West Africa. Although the mortality rate of the most recent outbreak isn't as high as in previous events, it's still the case that most people who become infected with Ebola will not survive. (The mortality rate is about 60 percent for the current outbreak, compared with 90 percent in the past, according to the National Institutes of Health.)

1. Rabies

2. HIV

3. Influenza

4. Mosquito-borne viruses

5. Rotavirus

 

 
Ed Rybicki's insight:

Amen!  I have a fondness for Ebola simply because it is so spectacularly nasty, but it has killed fewer people in 40 years than flu or rotavirus does in 1.

Seriously: just like charismatic animals like elephants and tigers get all of the headlines when it comes to being endangered, rather than the humble tree frog(s), so do Ebola and Marburg get all of the attention when it comes to reportage on virus epidemics / pandemics.

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Influenza A Virus Attenuation by Codon Deoptimization of the NS Gene for Vaccine Development

Influenza viral infection represents a serious public health problem that causes contagious respiratory disease, which is most effectively prevented through vaccination to reduce transmission and future infection. The nonstructural (NS) gene of influenza A virus encodes an mRNA transcript that is alternatively spliced to express two viral proteins, the nonstructural protein 1 (NS1) and the nuclear export protein (NEP). The importance of the NS gene of influenza A virus for viral replication and virulence has been well described and represents an attractive target to generate live attenuated influenza viruses with vaccine potential.

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The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing

The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing | Virology and Bioinformatics from Virology.ca | Scoop.it
PLOS Biology is an open-access, peer-reviewed journal that features works of exceptional significance in all areas of biological science, from molecules to ecosystems, including works at the interface with other disciplines.
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A Sensitive Tool for Detecting Indels

A Sensitive Tool for Detecting Indels | Virology and Bioinformatics from Virology.ca | Scoop.it

A team from Cold Spring Harbor Laboratory has released an algorithm, called Scalpel, for finding insertions and deletions in next generation sequencing data sets. Scalpel, which is open source and available for download on SourceForge, outperformed the popular tools GATK HaplotypeCaller and SOAPindel in test runs on both simulated and real whole human exomes.

Like other indel callers, Scalpel works by performing de novo assembly of regions of interest, so that misalignment to the reference genome cannot obscure the presence of an insertion or deletion. Scalpel's innovation is to repeatedly check its assembly before comparing to the reference genome, to account for simple sequence repeats that are a regular source of error in indel calling. When Scalpel assembles an exon, it collects reads that map to that exon (including partial matches), splits them into k-mers, and creates a de Bruijn graph to span the exon; however, if it detects repeats in the map, it iteratively increases the size of the k-mers by one base until the repeats are eliminated. This ensures that the final assembly of the exon is highly accurate while minimizing compute time.

 
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