Why do you think that this Ebola outbreak is spreading at rates so much higher than any other historical outbreak? Do you think that it is related to the fact that this outbreak is being transmitted from human to human with no continuous human-reservoir contact?
How prevalent are sequencing errors using the Next-Gen sequencing methods, and how are those errors found and fixed? In other words, what specifically constitutes a high-quality vs. low-quality genome when sequenced?
The authors worked to sequence the EBOV genomes of the EVD patients quickly in order to publish their work so that other scientists could pick the data up and move forward with it. What do you think the advantages and disadvantages of multiple parties being a part in pushing forward the research of the Ebola outbreak?
In the journal article, the authors stated "lineages of the three most recent outbreaks all diverged from a common ancestor at roughly the same time, around 2004." I am curious if any of the lineages have a higher mortality rate or have any signs of adaption to humans as the 'more common' reservoir/route of transmission, as of late.
What do you think was the point of sequencing cases that were suspected of EVD but tested negative? Those cases should not have contained the disease in the genome- why not just use an average person as a control?
Relative to the total genome of Ebola, the number of non-synonymous mutations found is very small. Given this information, do you think that the severity of the current Ebola outbreak is due to the new infrastructure of these developing countries or that these strains of Ebola are more potent?
From the Stephen, et al, article, how do you interpret Figure 4 D and E to show transmission clustering? Similarly, how does Figure 4 A and D represent the third Sierra Leone cluster?
Adding to Michaela's curiosity, if we are aware that the virus has multiple lineages from this single ancestor, is there a plan to address the issue that the disease may be evolving faster than we can find a concrete cure for even one lineage? Or can we assume that they are similar enough to be treated together, and therefore only have to worry about one lineage?
From the 'Camouflage and Misdirection' article, Ebola VP35 expression is shown to block protein kinase R (PKR) activity, causing enhanced expression of proteins leading to further ebola virus production. That being said, if PKR could be stimulated via an antibiotic, hormone or signal, could the spread and further production of the ebola virus be halted and eventually eliminated?
The paper states that there were 35 cases that were suspected for Ebola that tested negative for EBOV. Given the unique symptoms of EBV, what is the likely cause for these negatives? Is there a possibility that there are false negatives in their tests, and if so, does it affect the confidence in the results they propose?
In the first article, it discusses the extreme increase in cases in the 2014 outbreak compared to previous outbreaks. Do you believe this is due to a more virulent/transmissible strain or that the population is just denser and people are able to interact and come in contact with others easier? What does the given information in the article about the mutation rate indicate about the feasibility for a preventative measure such as a vaccine?
Even though Ebola is known for its high mutation rate, parts of the DNA sequence are often conserved, I noticed in the paper that they said they saw 8 mutations in normally conserved regions. Did you notice if they mentioned if how that affected those particular strains?
The Misasi & Sullivan paper noted that cytokine storms are characteristic of of fatal infection by Ebola. Do you think inhibition of specific cytokines (like TNF-alpha in this case) can balance out the immune response and prolong a patient's life? Or could that lead to further disruption of the immune response?
The main article states that Illumina sequencing was used to sequence these genomes and in the Next-Gen DNA sequencing paper it states that Illumina's dominant source of error is substitutions. What is the magnitude of error in such sequencing techniques and could it effect the fact that the researchers are honing in on single bp substitutions in between the patients?
From the Stephen, et al, article, ebola VP35 is shown to suppress cellular RNAi silencing and should splice viral RNA. Do you think that VP35 could be a possible target for drug therapy?
The first paper mentioned how they took 3 published sequences of the Guinean strain of Ebola and added them to their 78 Sierra Leonean sequences for a larger sample size, correcting what they believed to be "likely errors" from the other publication. How can they tell what are likely errors? Has there been any papers published in the past few months that cites and corrects this paper's sequences when adding it to their own sample size?
From the Gire, et al., reading, they mention how their genomic analysis identified other known pathogens (Lassa virus, HIV-1, etc.). Is it possible that the presence of these other pathogens could be influencing the Ebola outbreak rate?
From the Gire, et. al., reading, I noticed that five co-authors lost their lives in the making of this publication. Were any of their genomes subsequently sequenced? I wonder how their genomes would fit in with each of the 2 background lineages that originated in Guinea or if a similar transmission would result in similar/identical virus patterns.