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Early Detection of
Highly Pathogenic
Viral Infections
Ignacio Sanchez Caballero
Wednesday, May 1, 13
Infection
Wednesday, May 1, 13
Viremia
Infection
Wednesday, May 1, 13
Viremia
Infection
Transcriptional changes
Wednesday, May 1, 13
Lassa
Marburg
17
1 2 3 4 5 6 7 8 9 10 11 120
4 6 3 6 3
15 3 3 3 3 3
Days post-exposure
Number of
Samples
Wednesday, May 1, 13
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Lassa Marburg
Samples taken at the same time have similar gene expression values
Wednesday, May 1, 13
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Combined
Samples taken at the same time have similar gene expression values
Wednesday, May 1, 13
30
High
expression
Low
expression
Days post-infection
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
30
High
expression
Low
expression
Days post-infection
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
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random
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30
High
expression
Low
expression
Days post-infection
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
Probably
random
Probably significant
30
High
expression
Low
expression
Days post-infection
Significant high magnitude change
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
High
expression
Low
expression
Days post-infection
Probably
random
Probably significant
Significant high magnitude change
30
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
High
expression
Low
expression
Days post-infection
Probably
random
Probably significant
Not significant high magnitude change
30
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
High
expression
Low
expression
Days post-infection
Probably
random
Probably significant
Not significant high magnitude change
30
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
High
expression
Low
expression
Days post-infection
Probably
random
Probably significant
Significant low magnitude change
30
Wednesday, May 1, 13
No change
Increase
in expression
Decrease
in expression
High
expression
Low
expression
Days post-infection
Probably
random
Probably significant
Significant low magnitude change
30
Wednesday, May 1, 13
A subset of probes is differentially expressed 3 days post-exposure
Wednesday, May 1, 13
A subset of probes is differentially expressed 3 days post-exposure
Wednesday, May 1, 13
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Wednesday, May 1, 13
Lassa
Marburg
4
1 2 3 4 5 6 7 8 9 10 11 120
2
1
Days post-exposure
Number of
Samples
1
Test data set
Wednesday, May 1, 13
Lassa
Marburg
4
1 2 3 4 5 6 7 8 9 10 11 120
2
1
Days post-exposure
Number of
Samples
1 βœ–
Test data set
Wednesday, May 1, 13
Aim 1: Early detection of highly pathogenic viral infections
Compare the early transcriptional response of Lassa and Marburgβœ“
Wednesday, May 1, 13
Aim 1: Early detection of highly pathogenic viral infections
Compare the early transcriptional response of Lassa and Marburgβœ“
Identify a set of candidate biomarker genesβœ“
Wednesday, May 1, 13
Validate the current set of biomarkers using qPCR
Aim 1: Early detection of highly pathogenic viral infections
Compare the early transcriptional response of Lassa and Marburgβœ“
Identify a set of candidate biomarker genesβœ“
Wednesday, May 1, 13
Validate the current set of biomarkers using qPCR
Compare the differences in using sequencing to measure gene expression
Aim 1: Early detection of highly pathogenic viral infections
Compare the early transcriptional response of Lassa and Marburgβœ“
Identify a set of candidate biomarker genesβœ“
Wednesday, May 1, 13
Validate the current set of biomarkers using qPCR
Compare the differences in using sequencing to measure gene expression
Incorporate additional viruses to the analysis
Aim 1: Early detection of highly pathogenic viral infections
Compare the early transcriptional response of Lassa and Marburgβœ“
Identify a set of candidate biomarker genesβœ“
Wednesday, May 1, 13
Aim 2: Visualization of complex biological data
Develop a software tool to easily generate interactive plotsβœ“
Wednesday, May 1, 13
Aim 2: Visualization of complex biological data
Develop a software tool to easily generate interactive plotsβœ“
Make generating a dynamic plot as easy as a static one
Wednesday, May 1, 13
Aim 2: Visualization of complex biological data
Develop a software tool to easily generate interactive plotsβœ“
Make generating a dynamic plot as easy as a static one
Aim 3: Experimental training
Develop core skills in experimental virology
Wednesday, May 1, 13
Aim 2: Visualization of complex biological data
Develop a software tool to easily generate interactive plotsβœ“
Make generating a dynamic plot as easy as a static one
Aim 3: Experimental training
Develop core skills in experimental virology
Design and carry out experiments to determine viral and
host gene function
Wednesday, May 1, 13

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Early detection of highly pathogenic viral infections

  • 1. Early Detection of Highly Pathogenic Viral Infections Ignacio Sanchez Caballero Wednesday, May 1, 13
  • 5. Lassa Marburg 17 1 2 3 4 5 6 7 8 9 10 11 120 4 6 3 6 3 15 3 3 3 3 3 Days post-exposure Number of Samples Wednesday, May 1, 13
  • 6.          ο€ο€‚ο€ƒο€„ο€…ο€ƒο€†ο€‡ο€‚ο€ƒο€ƒο€‚ο€ˆο€‰ ο€„ο€ˆο€‡ο€Šο€‹ο€Œο€ο€Žο€ο€‹ο€ο€Š ο€†ο€‡ο€ˆο€‰ο€Šο€‹ο€‡ο€Œο€Šο€ο€… ο€†ο€‡ο€ˆο€‰ο€Šο€‹ο€‡ο€Œο€Šο€ο€Ž                    ο€… ο€… ο€…              ο€‡ο€†ο€„ο€ˆο€‰ο€Šο€‹ο€Œο€ο€‰ο€Žο€ˆ ο€†ο€‡ο€ˆο€‰ο€Šο€‹ο€‡ο€Œο€Šο€ο€‚ ο€†ο€‡ο€ˆο€‰ο€Šο€‹ο€‡ο€Œο€Šο€ο€Ž                                     Lassa Marburg Samples taken at the same time have similar gene expression values Wednesday, May 1, 13
  • 7.           ο€ο€‚ο€‚ο€ƒο€„ο€…ο€†ο€‡ο€„ο€†ο€ˆο€‰ο€‚ο€Šο€… ο€†ο€‡ο€ˆο€‰ο€Šο€‹ο€‡ο€Œο€Šο€ο€‚ ο€†ο€‡ο€ˆο€‰ο€Šο€‹ο€‡ο€Œο€Šο€ο€Ž                                          ο€… ο€…      ο€ˆ ο€ˆ ο€ˆ   ο€Šο€‹ο€Œο€Œο€‹ ο€ο€‹ο€Žο€ο€ο€Žο€‘ Combined Samples taken at the same time have similar gene expression values Wednesday, May 1, 13
  • 9. No change Increase in expression Decrease in expression 30 High expression Low expression Days post-infection Wednesday, May 1, 13
  • 10. No change Increase in expression Decrease in expression Probably random Probably significant 30 High expression Low expression Days post-infection Wednesday, May 1, 13
  • 11. No change Increase in expression Decrease in expression Probably random Probably significant 30 High expression Low expression Days post-infection Significant high magnitude change Wednesday, May 1, 13
  • 12. No change Increase in expression Decrease in expression High expression Low expression Days post-infection Probably random Probably significant Significant high magnitude change 30 Wednesday, May 1, 13
  • 13. No change Increase in expression Decrease in expression High expression Low expression Days post-infection Probably random Probably significant Not significant high magnitude change 30 Wednesday, May 1, 13
  • 14. No change Increase in expression Decrease in expression High expression Low expression Days post-infection Probably random Probably significant Not significant high magnitude change 30 Wednesday, May 1, 13
  • 15. No change Increase in expression Decrease in expression High expression Low expression Days post-infection Probably random Probably significant Significant low magnitude change 30 Wednesday, May 1, 13
  • 16. No change Increase in expression Decrease in expression High expression Low expression Days post-infection Probably random Probably significant Significant low magnitude change 30 Wednesday, May 1, 13
  • 17. A subset of probes is differentially expressed 3 days post-exposure Wednesday, May 1, 13
  • 18. A subset of probes is differentially expressed 3 days post-exposure Wednesday, May 1, 13
  • 19.            ο€ο€‚ο€ƒο€„ο€…ο€†ο€‡ο€ˆο€‰ο€ƒο€Šο€‹ ο€Œο€ο€‰ο€‰ο€ο€ƒο€†ο€…ο€ƒο€Žο€ο€…ο€‡ο€ο€…ο€ ο€†ο€‡ο€ˆο€ˆο€‡ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€• ο€–ο€‡ο€—ο€˜ο€™ο€—ο€”ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€• Wednesday, May 1, 13
  • 20.            ο€ο€‚ο€ƒο€„ο€…ο€†ο€‡ο€ˆο€‰ο€ƒο€Šο€‹ ο€Œο€ο€‰ο€‰ο€ο€ƒο€†ο€…ο€ƒο€Žο€ο€…ο€‡ο€ο€…ο€ ο€†ο€‡ο€ˆο€ˆο€‡ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€• ο€–ο€‡ο€—ο€˜ο€™ο€—ο€”ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€•            ο€ο€‚ο€ƒο€„ο€…ο€†ο€‡ο€ˆο€‰ο€ƒο€Šο€‹ ο€Œο€ο€‰ο€‰ο€ο€ƒο€†ο€…ο€ƒο€Žο€ο€…ο€‡ο€ο€…ο€ ο€†ο€‡ο€ˆο€ˆο€‡ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€• ο€–ο€‡ο€—ο€˜ο€™ο€—ο€”ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€• Wednesday, May 1, 13
  • 21.            ο€ο€‚ο€ƒο€„ο€…ο€†ο€‡ο€ˆο€‰ο€ƒο€Šο€‹ ο€Œο€ο€‰ο€‰ο€ο€ƒο€†ο€…ο€ƒο€Žο€ο€…ο€‡ο€ο€…ο€ ο€†ο€‡ο€ˆο€ˆο€‡ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€• ο€–ο€‡ο€—ο€˜ο€™ο€—ο€”ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€•            ο€ο€‚ο€ƒο€„ο€…ο€†ο€‡ο€ˆο€‰ο€ƒο€Šο€‹ ο€Œο€ο€‰ο€‰ο€ο€ƒο€†ο€…ο€ƒο€Žο€ο€…ο€‡ο€ο€…ο€ ο€†ο€‡ο€ˆο€ˆο€‡ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€• ο€–ο€‡ο€—ο€˜ο€™ο€—ο€”ο€‰ο€Šο€‹ο€Œο€ο€‡ο€Žο€‰ο€ο€‰ο€Œο€ο€‹ο€‰ο€‘ο€’ο€“ο€”ο€ƒο€•            ο€ο€‚ο€ƒο€„ο€…ο€†ο€‡ο€ˆο€‰ο€ƒο€Šο€‹ ο€Œο€ο€‰ο€‰ο€ο€ƒο€†ο€…ο€ƒο€Žο€ο€…ο€‡ο€ο€…ο€ ο€†ο€‡ο€ˆο€‰ο€Šο€‹ο€ˆο€Œο€ο€ˆο€Žο€ο€Šο€ο€Œο€‘ο€Œο€Žο€’ο€ˆο€Œο€“ο€”ο€•ο€‹ο€ƒο€– ο€—ο€ο€˜ο€˜ο€ˆο€‰ο€ˆο€ο€™ο€ˆο€Œο€ο€ο€Œο€ο€ˆο€Žο€ο€Šο€ο€Œο€‘ο€Œο€Žο€’ο€ˆο€Œο€“ο€”ο€•ο€‹ο€ƒο€– Wednesday, May 1, 13
  • 22. Lassa Marburg 4 1 2 3 4 5 6 7 8 9 10 11 120 2 1 Days post-exposure Number of Samples 1 Test data set Wednesday, May 1, 13
  • 23. Lassa Marburg 4 1 2 3 4 5 6 7 8 9 10 11 120 2 1 Days post-exposure Number of Samples 1 βœ– Test data set Wednesday, May 1, 13
  • 24. Aim 1: Early detection of highly pathogenic viral infections Compare the early transcriptional response of Lassa and Marburgβœ“ Wednesday, May 1, 13
  • 25. Aim 1: Early detection of highly pathogenic viral infections Compare the early transcriptional response of Lassa and Marburgβœ“ Identify a set of candidate biomarker genesβœ“ Wednesday, May 1, 13
  • 26. Validate the current set of biomarkers using qPCR Aim 1: Early detection of highly pathogenic viral infections Compare the early transcriptional response of Lassa and Marburgβœ“ Identify a set of candidate biomarker genesβœ“ Wednesday, May 1, 13
  • 27. Validate the current set of biomarkers using qPCR Compare the differences in using sequencing to measure gene expression Aim 1: Early detection of highly pathogenic viral infections Compare the early transcriptional response of Lassa and Marburgβœ“ Identify a set of candidate biomarker genesβœ“ Wednesday, May 1, 13
  • 28. Validate the current set of biomarkers using qPCR Compare the differences in using sequencing to measure gene expression Incorporate additional viruses to the analysis Aim 1: Early detection of highly pathogenic viral infections Compare the early transcriptional response of Lassa and Marburgβœ“ Identify a set of candidate biomarker genesβœ“ Wednesday, May 1, 13
  • 29. Aim 2: Visualization of complex biological data Develop a software tool to easily generate interactive plotsβœ“ Wednesday, May 1, 13
  • 30. Aim 2: Visualization of complex biological data Develop a software tool to easily generate interactive plotsβœ“ Make generating a dynamic plot as easy as a static one Wednesday, May 1, 13
  • 31. Aim 2: Visualization of complex biological data Develop a software tool to easily generate interactive plotsβœ“ Make generating a dynamic plot as easy as a static one Aim 3: Experimental training Develop core skills in experimental virology Wednesday, May 1, 13
  • 32. Aim 2: Visualization of complex biological data Develop a software tool to easily generate interactive plotsβœ“ Make generating a dynamic plot as easy as a static one Aim 3: Experimental training Develop core skills in experimental virology Design and carry out experiments to determine viral and host gene function Wednesday, May 1, 13