1. Introduction:
GenePool (Station X Inc) is a Software-­as-­a-­
Service platform that enables analysis of
patient-­derived genomics datasets and has
applications in research and clinical settings.
ImmPort is a database of immunology clinical
studies funded by NIAID. I had three main
objectives;; to develop a protocol for making
ImmPort data compatible with GenePool, to
validate the data by reproducing results of an
ImmPort study using GenePool, and to
potentially identify new findings. I developed a
protocol for transforming ImmPort data for
compatibility with GenePool, which may be
used to mirror the entire ImmPort repository
within GenePool. I was able to reproduce some
key results from the paper “Systems biology of
vaccination for seasonal influenza in humans”
by Nakaya et al. (2011) and identify some novel
results.
Meta-­Analysis of Studies Investigating Immune Response to Seasonal
Influenza Vaccination
Brittany Salazar, San Francisco, CA, Summer 2015
Project Overview: Acknowledgements
Many thanks to Sandeep Sanga (Station X Inc), Sanchita Bhatticharya
(UCSF), and Ravi Shankar (UCSF) for their help with the design of my
project and their helpful suggestions for putting together the
compatibility protocol.. Thank you to Richard Goold and Tod Klingler
and the rest of the team at Station X: Anish, Jeff, Edie, Adin, and
Antoanetta
Results:
Nakaya et al. Experimental Design:
Fig ure 1: Expe rimenta l d esign of t he Nakaya et a l. study (2011). (a) Sche ma tic
representation o f the experimen tal desi gn. Subjec ts were vaccina ted with the T IV
intram uscularly in three flu seasons, one cohor t was vaccinated wi th the L AIV intran asally
during the 2008-­20 09 flu season . Di fferen t assays and statis tical analyses were perfor med to
find molecular markers indicative of vaccine response.
Discussion:
Nakaya et al. found a negative correlation between
HAI response and CaMKIV expression levels, and
positive correlations between HAI response and
members of the LILR family, genes related to the
unfolded protein response, TNFRSF17, TNFSF13,
and CD38. TNFRSF17, TNFSF13, and CD38 have
roles in B-­cell development and differentiation – key
functions in the development of adaptive immunity. I
was able to replicate these findings to a certain
extent. The authors’ findings regarding CaMKIV
suggested to them that CaMKIV plays a role in B-­cell
differentiation, however, my analysis revealed a
modest at best correlation between CaMKIV levels
and HAI response. I found the correlation between
TXNDC5 and HAI response to be more significant,
however, TXNDC5 seems to play a less obvious role
in the development of immunity. Additionally, I was
successful in creating a protocol for adapting ImmPort
data for compatibility with GenePool.
References:
Nakaya, H.I., Wrammert, J., Lee, E.K., Racioppi, L., Marie-­Kunze, S., Haining,
W.N., Means, A.R., Kasturi, S.P., Khan, N., Li, G.M., et al. (2011). Systems
biology of vaccination for seasonal influenza in humans. Nat Immunol 12, 786-­
795.
a
b
Fig ure 2: Gene ex press ion thr ee days p ost vac cin atio n wit h TIV. G enePool software was
used to asses the expression levels o f various genes three days post vaccina tion w ith TIV.
Blue bars in dividuals wi th l ow H AI response– indica ting a p oor vaccine response – green b ars
indicate hi gh HAI responders. (a) levels o f Calciu m/cal modu lin depende nt kinase IV. Nakaya
et al . found a s tatistical ly signi ficant nega tive correla tion be tween C aM KIV expression and
HAI response. Here, that di fference seems less sign ifican t as ind icated by a high p-­value
(p>0.05) and th e b ar graph . (b) levels o f T XNDC5. Expression differences o f th is g ene seem
to be more statistically significant based on the low p-­value (p<0.005) and the bar graph.