Mining the Past to Predict the Species Jump Event 19 April 2011 Richard H Scheuermann PhD Department of Pathology UT Southwestern Medical Center Flu pandemics of the 20 th and 21 ID: 934202
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Slide1
The Informatics Crystal Ball:Mining the Past to Predict the Species Jump Event
19 April 2011Richard H. Scheuermann, Ph.D.Department of PathologyU.T. Southwestern Medical Center
Slide2Flu pandemics of the 20th and 21
st centuries initiated by species jump events1918
flu pandemic (Spanish flu
)
subtype H1N1 (avian origin)
estimated
to have claimed between 2.5% to 5.0% of the world’s population (20 > 100 million deaths)
Asian
flu (1957
–
1958
)
subtype H2N2 (avian origin)
1 - 1.5 million deaths
Hong Kong flu (1968 – 1969)
subtype H3N2 (avian origin)
between 750,000 and 1 million deaths
2009 H1N1
subtype H1N1 (swine origin)
~ 16,000 deaths as of March 2010
Slide32009 Pandemic species jump
Slide4Pandemic stages
Adaptive drivers
Slide5Basic reproductive number (R0)Total number of secondary cases per caseReasonable surrogate of fitness
Characteristics of pandemic viruses:R0H >1, andIn genetic neighborhood of viruses with R0R>1 and R0H<1
Adaptive drivers
Pandemic Viruses
(R
0
H >1)
Stuttering viruses
(R
0
R>1 and R
0
H<1)
Reservoir virus
(R
0
R>1 and R
0
H<<1)
A1
A2
Slide6Adaptive drivers
Pepin KM et al. (2010) “Identifying genetics markers of adaptation for surveillance of viral host jump” Nature Reviews Microbiology 8: 802-814.
Slide7Stuttering transmission and adaptive driversStuttering transmission can reveal adaptive drivers by evidence of convergent evolutionOdds of finding the same neutral mutation by chance in multiple species jumps is lowTherefore, finding same mutation in multiple independent species jump events is strong evidence for adaptive driver
Slide8Genetic convergence during species jumpVirus isolate groups from IRDAvian H5N1 (PB2) from Southeast Asia* up to 2003 (260 records) – reservoirs of source viruses
Human H5N1 (PB2) from Southeast Asia 2003-present (165 records) – many examples of independent species jumpsAlign amino acid sequence and calculate conservation scoreIdentify highly conserved positions in avian records (≤1/260 variants) (557positions/759) – functionally restricted in reservoirSelect subset in which two or more human isolates contained the same sequence variant – either due to human-human transmission or convergent evolution
*China, Hong Kong, Indonesia, Thailand, Viet Nam
Slide9Strain Search – PB2 avian H5N1 Southeast Asia up to 2003
Slide10260 PB2 records
Slide11Sequence variation analysis
Slide12Position order
Slide13Order by conservation score
Slide14My Workbench
Slide15Convergent evolution candidates
d
d
d
Slide16Surface exposed
PB2_A/MEXICO/INDRE4487/2009(H1N1)
Conservation score
All convergent evolution
candidates
586, 591, 627, 629
Slide17Convergent evolution candidates
Slide18E627K
Slide19E627K and species jump
Slide20K660R
Slide21SummaryHuman influenza pandemics are initiated by species jump events followed by sustained human to human transmission (R0H>1)
Multiple independent occurrences of the same mutation during stuttering transmission is evidence of convergent evolution of adaptive drivers – hypotheses for experimental testingSurveillance for adaptive drivers in reservoir species could help anticipate the next pandemic
N01AI40041