Outsmart Ebola Together Project: Statistics & Reflection

For the past semester, our group has been lending our computing power to World Community Grid's Outsmart Ebola Together Project.  In this project, researchers in the Ollmann Saphire laboratory of The Scripps Research Institute in La Jolle, California are using World Community Grid to search for drugs to treat patients infected with the Ebola virus.  The computational power donated by volunteers like us is being used to screen millions of compounds to identify those that show promise in disabling the Ebola virus.  The lab has identified two areas within the virus that are vulnerable and have the potential to be used as targets to hit in order to block key stages of the virus life cycle.  These target locations are:

• the surface protein on the Ebola virus that is solely responsible for infection of new human cells
• the shape-shifting "transformer" proteins of the Ebola virus, which adopt different forms at different times to achieve different functions

Once the best candidate drug molecules have been identified, further testings will be performed in order to ensure their potential use in this project.  Screenings like this save researchers from having to perform many years of laboratory work and bring us rapidly closer to finding an antiviral treatment for Ebola.

As of today, the Outsmart Ebola Together Project is only twenty-eight percent complete.  Throughout our time working with this group, our grid completed 9,406 units of work but there is still more to be done.  [See table below to view overall progress of this project]

The Outsmart Ebola Together Project has opened our eyes to both a different aspect of science and service.  Before this assignment, none of us had any idea about what grid computing is or how useful it can be to the scientific community.  It also made us realize that doing service work does not always require an extensive of amount of time and effort outside of our already busy schedules.  You can give back to your community in a big way by being aware of grid computing, downloading a program, and letting your computer do the rest.  We would like to thank Dr. Walker for opening our minds to grid computing and giving us this opportunity to make a difference!

Ebola Article Questions

Questions 1-6 are based on the PLoSOne article entitled “How Ebola Impacts Genetics of Western Lowland Gorilla Populations” by Le Gouar et. al (2009). 

1. In an evolutionary sense, why is it informative to study human influenza and its implications in gorillas? Describe and define the mechanisms that have increased the risk of interspecific disease transmission between humans and non-human apes.

a.      Great apes and humans share around 98% of their genetic material. This remarkable similarity means that gorillas are susceptible to many human viruses and vice versa. With this insight, scientists have been able to gain a better understanding of the mechanisms that allow the transmission of disease between humans and non-human apes. Transmission of disease between these two groups typically occurs through various forms of interaction. Tourist, conservation scientist, and poachers are just a few examples of ways in which humans and apes come in contact with one another and open a door for interspecific disease transmission. Censored humanly interaction is important in the future in order to prevent both humans and apes from further infection.

2. Generally speaking, what are the evolutionary consequences of bottlenecks caused by infectious disease outbreaks?

a.      Generally speaking, population bottlenecks arise when a population’s size decreases over the duration of at least one generation. Genetic drift acts at a faster rate to reduce genetic variation in small populations. Consequently, undergoing a bottleneck could potentially reduce a population’s genetic variation immensely, even if the bottleneck does not exist for many generations. Reduced genetic variation results in the population being unable to adapt to new selection pressures, like climatic change or a shift in available resources, because the genetic variation that selection would act on may have already drifted out of the population.

If there were to be an infectious disease outbreak in a species, this would immensely affect a population. The population would be extremely small due to the bottleneck, therefore the genetics of the population would be very similar. Thus, making an infectious disease very detrimental to a population that has undergone the bottleneck phenomena.    

3. What measures of variation did the authors use to assess variation in the gorilla populations pre- and post-outbreak?  What did they find?

a.      In order to assess the variation in the gorilla populations pre- and post-outbreak, the authors measured: marker polymorphism, impact of mortality events on genetic diversity, changes in allele frequencies, immigration, and selection pressure.  By the end of the study, the authors were able to conclude that although there was an absence of genetic diversity loss after the Ebola epidemic, there were some temporal changes of allele frequencies in the gorilla populations.  

The authors attribute social organization, migration of both sexes, and low genetic structure between populations to lack of genetic diversity loss after the demographic crash.  Although the state of genetic diversity remains stable for now, the authors believe that these results could change in the near future.  This positive result could have also resulted from the fact that there was a high enough effective population size during the short amount of time surveyed after the decline.  With more time and data, the authors would have been able to draw a more precise conclusion on the effect the Ebola outbreak had on the genetic diversity in the gorilla populations.

In regards to the temporal changes of allele frequencies in the gorilla populations, it is believed that the cost of sociality induced by Ebola and the sex-biased dispersal of the species could have been the cause.  Through social organization and migration of both sexes, the authors hope that the gorillas will be able to rebuild their population without extreme effects from the Ebola epidemic.

4. Why is genetic variation important to a population (hint: revisit the Crotaphytus paper)?

a.      The Western lowland gorilla, a critically endangered species, shows the consequences of the lack of variance in a population. The gorilla population lost its genetic diversity because of a disease around 300 years ago, this caused a bottleneck effect. This bottleneck effect caused the loss of genetic diversity through an increase of inbreeding and the fixation of alleles. If the Gorillas had more variance, a disease like Ebola wouldn’t wipe out the entire population because the population wouldn’t be identical. With more genetic variation the gorillas would also be more able to adapt to their environments. If there is no gene flow in the population, then variance can’t occur, which again would lead to the fixation of alleles.

5. Did evolution occur between pre- and post-epidemic gorilla populations?  How do you know?  Which evolutionary mechanism(s) is/are thought to be operating in these populations?

a.      In the Lokoué population both pairwise F_ST analyses and tests of temporal changes in allele frequencies agreed that no changes occurred and therefore there was no evolution that occurred in the Lokoué population. In contrast, the Lossi population experienced significant temporal changes in allele frequencies were revealed at for four loci (D1s550 n = 12, D4s243 n = 8, D16s2624 n = 13, and vWF n = 12). We know evolution occurred because for these loci Waples' temporal tests were performed to investigate whether sampling error and genetic drift alone could explain the heterogeneity in allele frequencies over time. A significant test implies that sampling error and genetic drift were not sufficient to explain the differences in allele frequencies. The tests were significant for D16s2624 and vWF for all the value of Ne tested and therefore genetic drift and sampling error. The tests for D1s550, and D4s243 loci in Lossi were not significant. Those results indicate that for the Lossi population and the loci D16s2624 and vWF other factors than sampling error and genetic drift were responsible for the observed allele frequency changes between the pre- and post-epidemic samples.
  There are a few explanations for the absence of genetic diversity loss. In the Lokoué population, the absence of loss of genetic diversity is hypotheisezed to be a result of immigration in post-epidemic population since genetic diversity levels were in the same range than those previously published on Western lowland gorilla. In the Lossi population, In Lossi, no immigration from the peripgery had been detected. Another likely explanation for the absence of allelic diversity loss is a high enough remnant effective population size and the short time elapsed after the decline.
  In contrast, temporal changes of allele frequencies were observed in the Lossi population. The temporal heterogeneity is small for some locus (D1s550 and D4s243) and can be explained by drift or sampling error. However, other factors than drift and sampling errors were responsible for the observed allele frequency changes between pre and post-epidemic samples for two loci (D16s2624 and vWF) of the Lossi population. One hypothesis for the change in allele frequency at the two speciiced locus is the Ebola disease induced a non random mortality through selection in the Lossi population. A second possibility for the changes in allele frequencies between pre and post-epidemic samples in the Lossi population could result from evolutionary survival bias. This survival bias could have led to a bias composition of sampled individuals in the post-epidemic sample.

6. Why is it important to study protein folding/misfolding in Ebola?

a.      It is important to study the protein folding/misfolding in Ebola because the protein folding/misfolding determines the structure of the protein. Since the structure of a protein determines its function, once the structure is determined drugs can be developed and used to disrupt the function of the Ebola protein. On the topic of Ebola protein structure Zygmunt Derewenda, a biophysicist at the University of Virginia in Charlottesville, says, “When you have a protein with a novel amino-acid sequence, you never know if the structure is going to fall into one of the known families or if it’s going to be something new.” The initial, basic research on Ebola’s structure is important because it will tell us how Ebola operates once it infects a host, and also more importantly how to combat the virus.

Article link: file:///C:/Users/Alyson/Downloads/Ebola%20paper.pdf