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The Future of Viral Diagnostics: One Test For Every Human And Animal-Borne Virus
#1
This is post no. 1 under the main topic.
The Future of Viral Diagnostics: 

One Test For Every Human and Animal-borne Virus




[Image: 770px-Ebola_virus_(2).jpg]

The Ebola Virus






INTRODUCTION:

A September 2015 study published in the American medical journal Genome Research examines a revolutionary new diagnostic method known as “Enhanced Virome Sequencing Using Targeted Sequence Capture,” or ViroCap.

Developed jointly by the McDonnell Genome Institute and the Department of Pediatrics at Washington University School Of Medicine, the test claims to detect nearly all viruses which affect both humans and animals, and with far greater accuracy than standard diagnostic techniques.

This unique synthesis of scope and precision is expected to yield a wide range of health-care benefits for all people, from identifying lethal viruses, treating common infections, perhaps even the discovery of new, previously unknown diseases.





THE STANDARD MODEL: METAGENOMIC SHOTGUN SEQUENCING


Before looking at ViroCap an investigation of the prevailing technique is required. This way, the reader can better judge how the two systems compare.

The current model used in analyzing viruses is known as Metagenomic Shotgun Sequencing (or MSS), so called because the DNA sequence is “randomly sheared into small pieces” like a shotgun blast (California State University).  It can be described thus: 


Quote: "a relatively unbiased, culture-independent method in which nucleic acid extracted from a sample is sequenced [and] classified based on similarity to reference genomes. This approach allows comprehensive study of the viral component...."

Genome Research (September 22, 2015)

[Image: Whole_genome_shotgun_sequencing_versus_H...encing.png]

MSS:  Metagenomic Shotgun Sequencing


Or to put it in simpler terms, the benefits of MSS include:

  • Providing vital genetic information
  • Ability to classify data into groups
  • Culture-independence (samples do not have to be grown in a lab and can be taken directly from a patient/environment) 

MSS is “particularly useful to studies of the human microbiome, or in layman’s terms, all of the bacteria/viruses/fungi that live in our bodies,” explains MassGenomics.org, an American medical blog dedicated to in-depth analysis of the latest research papers.

However, MSS also has its drawbacks.

According to Dan Koboldt, head of the Human Genetics Analysis Group at Washington University's Genome Institute, “Most efforts to chart the human microbiome have focused on bacteria [which have] relatively stable genomes....Viruses, in contrast, are somewhat under-studied. Part of that is due to the small size and highly variable nature of viral genomes.”


[Image: 593px-Skin-Microbiome-Human.png]
The Human Microbiome


Although MSS is well-adapted for studying the human microbiome, the quote above reveals most of these inquiries have focused on bacterial genomes due to their relative simplicity. Viruses, however, are far more complex and volatile, and therefore less suited to the MSS model.

Another significant flaw of MSS and various diagnostic techniques is their lack of precision. Identifying the countless viruses which infect humans can prove difficult, often requiring several unnecessary tests before a correct diagnosis is found. “That’s because current tests aren’t sensitive enough to detect low levels of viral bugs,” say researchers at Washington University, or they're “limited to detecting only those viruses suspected of being responsible for a patient’s illness.”

Despite its advantages, the statement above shows MSS as less than ideal when it comes to pinpointing viruses. Either the test is not keen enough to find more elusive strains, or multiple attempts are required before determining the correct illness. 

This makes the present system of diagnosing viruses a process of elimination. But sometimes patients do not have any time to spare; while their doctors scramble to learn the cause of their sickness the patient may already be dying.

The recent Ebola outbreak is vivid proof of that reality.

According to a September 2015 report from the World Health Organization, the Ebola virus has left over 11,300 dead. If, however, the lethal virus had been correctly diagnosed back in December 2013, that may have prevented it from spreading beyond Guinean borders into neighboring regions and eventually to faraway nations such as Italy, Spain, the United Kingdom and America.



[Image: 14632566347_50dabfef42_b.jpg]


HEALTH-CARE WORKERS TAKING PRECAUTIONS AGAINST EBOLA


All of these facts and statements demonstrate just how flawed our present day system can be for identifying viruses.

Now let's compare it to the ViroCap test. 




VIROCAP: WHAT IS IT AND HOW DOES IT WORK?


ViroCap is an alternate method used to enrich the genome sequence of a virus. To develop the test, researchers targeted unique stretches of DNA and RNA from every known group of viruses that infect both humans and animals, according to researchers at Washington University.

The creators of ViroCap describe their new technology as: 


Quote: a comprehensive viral targeted sequence capture panel that could be used to 1) assess all viruses known to infect vertebrate cells and 2) detect divergent viruses. To this end, we created ViroCap, a targeted sequence capture panel that enhances the detection of a
comprehensive set of viruses with vertebrate hosts.”
Genome Research (September 22, 2015)


In short, ViroCap differs from MSS in that it specifically targets a certain group of viral genes. Unlike a shotgun blast, ViroCap is more akin to a sniper rifle. However, the data it yields is both detailed and comprehensive.

Additionally, the new test is far more ambitious in scope than MSS: its goal is to analyze all viruses that infect vertebrate cells and even variant strains.

Now as to the question of evidence....




CLINICAL STUDIES 


To prove ViroCap's superiority researchers performed two human clinical studies, comparing MSS against ViroCap's targeted sequence capture to see which was better at detecting DNA and RNA viruses.

(Note: the virus samples used in both experiments had already been tested positive by the virology lab at St. Louis Children's Hospital)


Process


In each study the same data was sequenced: first, without targeted sequence capture (pre-capture), and then by targeted sequence capture using ViroCap (post-capture). 


Experiment 1:


A total of 14 viruses were present in the clinical samples.


Results:

  • 10 viruses were found using MSS pre-capture method
  • 14 viruses were found using ViroCap's targeted sequence capture
  • Median percent increase of viral reads was 674 (range >13 to 9335)
  • Median breadth of coverage increased from 2.1% (range 0 to 89.8%) to 83.2% (range 0.8 to 100%)

Researchers describe their findings thus:


Quote:
 Targeted sequence capture resulted in dramatic improvements in all sequence coverage metrics...including number and percent viral reads, breadth and depth of coverage...."
— Genome Research (Sept 22, 2015)


Primary results have so far established ViroCap as a leader in accuracy, having identified 100% or 4 more viruses than MSS with its targeted sequence capture approach.


Experiment 2:


A total of 18 viruses were present in the clinical samples.


Results:

  • 11 viruses were found using MSS pre-capture method
  • 18 viruses were found using ViroCap's targeted sequence capture
  • Median percent increase of viral reads was 296 (range >56 to 2,722)
  • Median breadth of coverage increased from 2.0% (range 0 to 99.9%) to 75.6% (range 13.5 to 100%)

Once more ViroCap was the superior of MSS.  In Experiment 2, researchers “again found that targeted sequence capture resulted in dramatic improvements in sequencing parameters.”

The evidence is strong: combining data from both experiments, we discover ViroCap identified a total of 32 viruses compared to MSS's 21, an increase of 52%.






ADDITIONAL EXPERIMENT DATA

  • ViroCap can generate complete/nearly complete genome sequences directly from clinical samples without first culturing the virus

  • ViroCap can identify RHINOVIRUSES by type

  • ViroCap can distinguish between HERPESVIRUS 6B and 6A, ADENOVIRUS types A and C, and POLYOMAVIRUSES JC and BK

  • MSS identified INFLUENZA A pre-capture, but ViroCap classified it specifically as type H3N2 post-capture

  • ViroCap also sequenced ENTEROVIRUS D68 genome directly from clinical samples

[Image: 482px-Rhinovirus.PNG]

RHINOVIRUS

Once again the facts reinforce ViroCap's targeted sequence capture over the conventional MSS model. Not only can it fully map the genome sequences of a virus, but it does so with remarkable precision.

The significance of this last point cannot be overstated:


Quote:
...while standard testing identified a virus as influenza A, which causes seasonal flu, [ViroCap] indicated that the virus was a particularly harsh subtype called H3N2. Last flu season, H3N2 contributed to some 36,000 deaths in the United States.”
Washington University (September 29, 2015)

In the case above, standard MSS testing detected the influenza A virus but failed to pinpoint the H3N2 strain. 
The result? 

36,000 deaths last year in the United States alone; 28,800 in England (DailyMail.uk), and over 600 in Canada (Public Health Agency of Canada). 
Media outlets publicized the large death-toll with headlines like “Flu Season Declared An Epidemic Due To Mutating H3N2 Virus, Ineffective Vaccines (International Business Times).”


[Image: 500px-InfluenzaNomenclatureDiagram.svg.png]

H3N2 Strain of Influenza A


But as the experiments revealed, ViroCap was able to precisely identify the virus subtype, “And in some patients – particularly young children, older adults...knowing that the H3N2 strain is present may alter treatment (Washington University).” 

ViroCap's ability to collect detailed genetic data may have helped identify the H3N2 strain of Influenza last year, giving doctors vital knowledge of how to fight the virus and lower the immense death-count.  







VIROCAP—POTENTIAL MEDICAL BENEFITS


Because ViroCap is such a new medical development studies on its real-world use have yet to be published. According to Washington University it may take several years before the test is clinically available.
So, using my own reasoned arguments backed by proven facts, the following is a list of probable (though still theoretical) future benefits ViroCap may bring.


LOWER COST OF HEALTH-CARE


ViroCap's advantage lies in its precision and ability to detect the most elusive viruses, and for this reason I believe it will lower medical bills. “While PCR tests can screen for up to about 20 similar viruses at one time, it seems that ViroCap could theoretically test for virtually any virus,” reports MedicalNewsToday.com.  

Fewer tests mean lower prices. For example, diagnosing Ebola costs roughly $1000 (Mirror Daily) but according to Genome Research, “ViroCap achieves better viral coverage while requiring...fewer total sequence reads. This increased efficiency has the potential to lower sequencing costs.”

Therefore, it is logical to assume that one of ViroCap's potential benefits would be reduced health-care payments from less testing.



IMPROVED LIFE EXPECTANCY


Researchers at Washington University state: “current tests...are limited to detecting only those viruses suspected of being responsible for a patient’s illness.”  

Compare that to ViroCap:


Quote:
 “With this test, you don’t have to know what you’re looking for...It casts a broad net and can efficiently detect viruses that are present at very low levels...especially useful in situations where a diagnosis remains elusive after standard testing...” 

Washington University (September 29, 2015)


Doctors will no longer be limited to specific tests which they believe may help them identify a patient's illness, or move from one diagnostic tool to another in the hunt for obscure viruses, but can use a single, far more efficient means of finding the correct diagnosis.

And because it “casts a broad net,” ViroCap can reveal diseases no one was searching for but were nonetheless present. Simply put: the new test can save lives by detecting the nearly undetectable, or identify future health risks through early diagnosis.


BETTER PATIENT CARE


Instead of enduring multiple tests which may cause pain or distress (especially among children, the elderly and mentally impaired) ViroCap would cut down the number of procedures to just one, making hospital care less invasive for patients.

Less testing also reduces risk of infection. The World Health Organization states that every year “hundreds of millions of patients are affected by health care associated infections around the world.” 

As for their impact:     



Quote:
 “health care-associated infections create additional suffering and come at a high cost for patients and their families...prolong hospital stays, create long-term disability, increase resistance to antimicrobials, represent a massive additional financial burden for health systems...and cause unnecessary deaths.”

World Health Organization (May 5, 2011)


Among several leading causes of infection WHO cites “prolonged and inappropriate use of invasive devices.”

The key word is devices—meaning more than one.



[Image: Contaminated_surfaces_increase_cross-transmission.jpg]


HOSPITAL RELATED INFECTIONS ARE EVER-PRESENT


Of course, not all medical equipment is used for diagnostic purposes, but many still are. And if greater frequency of testing increases the chances of infection, ViroCap's single diagnostic capabilities would reduce the odds of contagion, thereby saving lives and money.



BETTER VETERINARY CARE + SAFER HUMAN-ANIMAL INTERACTIONS


For a vast majority of readers ViroCap's most obvious benefit would be improvements to human health, but it's also a blessing for pet owners and animal lovers. As stated previously, “researchers targeted unique stretches of DNA and RNA from every known group of viruses that infect both humans and animals.”

ViroCap has the power to identify all animal-borne viruses, which means owners can ensure their beloved pets receive the best care from veterinarians. Early detection can lead to early treatment, so our pets can live longer and healthier lives.


[Image: 7096472197_0eb4d836ab_b.jpg]


VIROCAP MAY HELP PETS LIVE LONGER THROUGH ACCURATE DETECTION OF VIRUSES


Furthermore, endangered species will have a better chance of surviving with this new technology. Zoos and animal sanctuaries often have breeding programs for at-risk creatures, and being able to identify and treat viruses quickly (such as the canine distemper virus which killed four rare Bengal tigers last year—theguardian.com) can prolong their lives, increase populations, and eventually free them from the constant threat of extinction.



[Image: Army_veterinarians,_an_ill_tiger_cub_and...n_Iraq.jpg]


VIROCAP HAS THE POTENTIAL TO SAVE ENDANGERED SPECIES THROUGH EARLY AND ACCURATE VIRUS DETECTION


Lions, tigers, polar bears and leopards, these rare and majestic creatures may have a brighter future thanks to ViroCap.

Lastly, safer human-animal interaction can be achieved through ViroCap's keen ability to detect viruses. According to livescience.com, “About 60 percent of all human diseases and 75 percent of all emerging infectious diseases are zoonotic,” meaning they're passed from animals to humans.

Incredibly, over half the illnesses which affect people actually originate in the animal kingdom. And we're already familiar with some of them: Ebola, bird flu, West Nile, Hantavirus.

In most cases infection is spread to humans via livestock (livescience.com), but with ViroCap's ability to detect every known animal virus, there is a strong possibility of lowering the chances for transmission.
Therefore interactions with nature become less of a risk to our health.



[Image: EbolaCycle.png]

HOW VIRUSES ARE PASSED FROM ANIMALS TO HUMANS (ZOONOTICS) 






CONCLUSION


Although ViroCap is still years away from becoming clinically available it holds great potential. Its unique capacity for scanning a wide range of diseases coupled with its knife-like precision make it a vital tool in the identification and treatment of viruses.

Both humans and animals have a lot to gain from its success: lower health-care bills, increased efficiency and diagnostic speed, and quicker treatment, all of which promise longer, healthier lives.


The fact that the inventors of ViroCap are making their technology “publicly available to scientists and clinicians worldwide, for the benefit of patients and research” (Washington University) serves to help all nations, peoples and animals.






The following is a link to entire study published in Genome Research:  http://genome.cshlp.org/content/early/20...9.115.long







LIST OF SOURCES (In Alphabetical Order):



Brazier, Yvette. (2015). “A single test could detect almost any virus.” Medical News Today. Retrieved from http://www.medicalnewstoday.com/articles/300259.php


Bryner, Jeanna. (2012). “13 Animal-to-Human Diseases Kill 2.2 Million People Each Year.” livescience.com http://www.livescience.com/21426-global-zoonoses-diseases-hotspots.html


Glum, Julia. (2014) “2014-2015 Flu Season Declared An Epidemic Due To Mutating H3N2 Virus, Ineffective Vaccines.” International Business Times. Retrieved from http://www.ibtimes.com/2014-2015-flu-sea...es-1770728


Koboldt, Dan. (2015). “How to Catch a Virus: Targeted Capture for Viral Sequencing.” Mass Genomics. http://massgenomics.org/2015/10/targeted...ncing.html


Moore, Robert. (2015). “MAJOR MEDICAL BREAKTHROUGH: NEW VIRUS TEST KIT MIGHT DETECT ALL VIRUSES.” Mirror Daily. Retrieved from http://www.mirrordaily.com/breakthrough-...ses/24469/


Rogers, Amy. (2008). “Shotgun Sequencing.” California State University. Retrieved from http://www.csus.edu/indiv/r/rogersa/Bio1...hotgun.pdf


Todd N. Wylie, Kristine M. Wylie, Brandi N. Herter, and Gregory A. Storch. (2015). “Enhanced Virome Sequencing Using Targeted Sequence Capture.” Genome Research. Retrieved from http://genome.cshlp.org/content/early/20...9.115.long


(2015) “Influenza surveillance.” Public Health Agency of Canada. Retrieved from http://www.phac-aspc.gc.ca/influenza/ass...g.php#fig2


(2014). “Dog virus threatens India's dwindling tiger population.” The Guardian. Retrieved from http://www.theguardian.com/world/2014/ja...dia-tigers


(2011) “Health care-associated infections FACT SHEET.” World Health Organization. Retrieved from http://www.who.int/gpsc/country_work/gps...eet_en.pdf


(2015) “New test detects all viruses that infect people, animals.” Washington University In St. Louis. https://news.wustl.edu/news/Pages/28833.aspx












 
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#2
This is post no. 2 under the main topic.
ViroCap: Additional Medical Benefits


In the preceding article we analyzed the potential medical gains of the new ViroCap test. However, because the technology is so new there are no comprehensive studies performed on its real world application, which is why all the benefits listed are purely speculative.

At the same time it's effectiveness has been proven through clinical studies.

What follows is a list of additional health-care benefits ViroCap may bring in the future. All opinions are backed by facts and expanded upon through my own reasoned arguments. 






DIVERGENT STRAINS/BETTER CURES:


Besides its aptitude for detecting every known virus researchers also used ViroCap to identify divergent strains of infectious diseases. During an experiment, they tested multiple samples of the anellovirus, “a highly divergent group of ssDNA viruses which have a common genome structure, but may have up to 30 to 50% nucleotide sequence diversity....”

The results? In the own words:


Quote:
"targeted sequence capture using...ViroCap [allowed] us to identify variant virus sequences having as low as 58% nucleotide sequence identity."
Genome Research (September 22, 2015)


The above data further emphasizes ViroCap's accuracy: not only does it excel at pinpointing viruses, but it transcends other methods in locating divergent strains.



[Image: 2000px-Influenza_geneticshift.svg.png]

DIVERGENT STRAINS OF A VIRUS




Being able to identify a particular strain of infection, such as the complex and variable allenovirus, can help scientists to invent better cures—vaccines that specifically target a viral strain rather than the general group to which it belongs.

We saw in the preceding article how the 2014 flu season resulted in thousands of deaths and was declared an epidemic by the Center for Disease Control (dailymail.co.uk), all because standard testing failed to identify the H3N2 strain of Influenza which ViroCap successfully detected.

In fact, “about half of the H3N2 viruses don't match up with the corresponding strain in this year's vaccine (Center for Infectious Diseases Research and Policy).” 



[Image: ReverseGeneticsFlu.svg]

CREATING NEW VACCINES TO COMBAT FLU STRAINS


A cure is only effective if it works, and knowing how to distinguish between viral subtypes—which ViroCap has been proven to do—allows researchers to react quicker and create vaccines which target those unique subtypes and mutations soon after they happen. 


In the case of anellovirus, “the high degree of sequence variation present in TTV and related anelloviruses can pose technical problems for reliable detection by PCR or other amplification methods (Journal of General Virology).”  But we've seen how ViroCap is far superior to PCR and other technologies, and in the future may completely prevent (or at least reduce) the spread of all epidemics, first through early detection, then through identification of specific strains, both of which result in more effective cures.   








BROADER USE:


The inventors of ViroCap assert that their test,


Quote:
 "could also be modified into a tool for broader pathogen identification, which might include a comprehensive set of human pathogens: genes from viruses, bacteria (e.g. toxin genes, antibiotic resistance genes), fungi, protists, and other microbes."
Genome Research (September 22, 2015)



Not only does ViroCap hold the potential to classify viruses and their many variants, but it may be able to determine other pathogens, bacteria, genes and even fungi. This would potentially make the new technology indispensable to doctors, biologists, and environmental scientists.



[Image: Fungi_collage.jpg]


VARIOUS FUNGI WHICH VIROCAP MAY POTENTIALLY DETECT



Its scope would extend beyond the field of medicine to include natural as well. Furthermore, it wouldn't be limited to diagnosing only viruses, but could also pinpoint bacterial infections and toxins.





RESEARCH POTENTIAL:


One the most exciting benefits of ViroCap would be to gather data:  


Quote:
"Its research applications are far reaching, allowing a new, higher resolution view of eukaryotic DNA and RNA viruses in the microbiome. ViroCap should also help realize the potential of MSS as a clinical diagnostic tool that can simultaneously detect viruses as well as provide immediate characterization including taxonomic assignment, strain typing, virulence characteristics, and anti-viral drug resistance genotyping."
Genome Research (September 22, 2015)


[Image: InvestigadoresUR.JPG]


RESEARCH SCIENTISTS WORKING ON NEW CURES


In other words, ViroCap's ability to collect vast amounts of data has significant real world functions, including: 
  • 1) more detailed images of viruses (helpful for studying infections and learning their complex behaviors and mutations)
  • 2) rapid virus detection and classification (necessary to build databases of new viruses or to more accurately categorize older ones) 
  • 3) identifying new viral strains (vital for combating lethal variations of Influenza and preventing epidemics)
  • 4) understanding how and why viruses are resistant to certain drugs
The comprehensive data amassed by ViroCap may not have immediate payoffs, but in time researchers will be able to better understand the way viruses behave, evolve, and build tolerance to medications—all of which are sure to result in better treatments and a healthier society.






LIST OF SOURCES:


Todd N. Wylie, Kristine M. Wylie, Brandi N. Herter, and Gregory A. Storch. (2015). “Enhanced Virome Sequencing Using Targeted Sequence Capture.” Genome Research. Retrieved from http://genome.cshlp.org/content/early/20...9.115.long


Nye, James. (2014). “America gripped by flu epidemic.” DailyMail.co.uk. Retrieved from http://www.dailymail.co.uk/news/article-2891221/CDC-warns-nation-brink-flu-epidemic-virulent-mutated-strain-sweeps-22-states.html


Roos, Robert. (2014). “CDC's flu warning raises questions about vaccine match.” Center For Infectious Disease Research and Policy. Retrieved from http://www.cidrap.umn.edu/news-perspecti...cine-match


Shoko Nishiyama, Bernadette M. Dutia, James P. Stewart, Anna L. Meredith, Darren J. Shaw, Peter Simmonds, and Colin P. Sharp. (2014). “Identification of novel anelloviruses with broad diversity in UK rodents.” Journal of General Virology. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059270/
 
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