He Lab Overview:
Systems Biology Studies of Host-pathogen
Interactions and Vaccines
(Workshop on Data, Text, Web & Social Network Mining)
Yongqun “Oliver” He
Unit for Laboratory Animal Medicine
Department of Microbiology and Immunology
Center for Computational Medicine and Bioinformatics
University of Michigan Medical School
Ann Arbor, MI 48109
Overview
Brucella and Brucellosis
• Brucella: intracellular bacterium that causes
most common zoonotic brucellosis in humans
and animal
• Lab focuses: Brucella pathogenesis & vaccine
• Lab goal: Develop a human Brucella vaccine.
Caspase-2 mediated
cell death of
macrophages
induced by Brucella
vaccines but not by
virulent Brucella
strains
Brucella vaccineinfected
macrophages
from wild type
mice
Brucella
vaccine-infected
macrophages
from Caspase-2
knockout mice
Light
microscopy
Annexin V-PI
fluorescence
miniTUBA: dynamic Bayesian
network (BN) analysis system
-- http://www.minituba.org/
Brucella_wboA_mutation
Nfkb2
Casp1
Tnf
Nfkbia
Casp2
Il1b
Casp7
miniTUBA: A pipeline –
- data input,
- missing data prediction,
- dynamic BN calculation,
- prediction of future event,
- output visualization
Predicted network of Brucellainduced macrophage cell death
Irak2
Macrophage_death
Experimentally Confirmed:
Casp2, Tnf, Nf-kb, Casp1
BN+1: Bayesian network expansion
-- Iteratively test all possible genes
BN+1: find pathway hidden factors
Confirmed
BN+1 identified new ROS and
biofilm regulators (PMID: …)
Limix: Literature mining & curation system
-- http://www.limix.org
• Limix allows us to manually curate a large amount of
high quality data in a short period of time.
• Support: literature search; data input, edition and
submisison; data review before publication; versioning
PHIDIAS: Pathogen-Host Interaction
Data Integration and Analysis System
-- http://www.phidias.us/
• Focus: PHI – Pathogen-host interaction
• Statistics: ~60 pathogens, >700 genomes
• Model organism: Brucella
VIOLIN: Vaccine Investigation
and Online Information Network
-- http://www.violinet.org
• Overall goal: A vaccine research
database & vaccine data analysis system
• Manually curated 454 vaccines from 73
pathogens
• Many programs, e.g., Vaxign (Vaccine
Design) and VO (Vaccine Ontology)
VIOLIN web cover page
Vaxign: Vaccine Design
--the 1st web-based vaccine design system
based on reverse vaccinology
http://www.violinet.org/vaxign
Query
Web
Browser
Results
Input
(PHP/HTML)
Dynamic
Computation
Filter
or: Query
Output
(PHP/HTML)
Retrieve
Process
(PHP/SQL)
Subcellular
Localization
Transmembrance
Domains
Adhesin
Probability
MySQL
Database
PHP/SQL
MHC-Epitope
Binding
Sequence
Conservation
Functional
Analysis
(DAVID)
Transmembrance
Topology
(α-helix, b-barrel)
Similarity to
Host Proteins
Sequence
Exclusion
• Reverse vaccinology: predict vaccine targets first
from bioinformatics analysis of genomes
• Applications: UPEC, Brucella, Francisella, …
VO: Vaccine Ontology
-- a community effort
• Vaccine Ontology (VO): Controlled vocabulary of terms
and relations (“ontology”) in the vaccine domain
• Allow computers to understand and analyze data
• Support computer-assisted reasoning
http://www.violinet.org/vaccineontology
VO-based literature mining
• VO-based SciMiner: to index vaccine literature
based on VO terms.
o Joint work with Junguk Hur, Eva Feldman
• VO-based literature discover of IFNG interaction
networks
o Joint work with Arzucan Özgür, Dragomir R.
Radev
Acknowledgements
He Laboratory / U of Michigan (UM)
UM Collaborators:
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Peter Woolf
Brian Athey
Harry Mobley
Arzucan Özgür, Dragomir R. Radev
Junguk Hur, Eva Feldman
Dongjuan Dai, Chuanwu Xi
Vaccine Ontology Collaborators:
* **
***
* Dr. Fang Chen
** Andrew Hodges
*** Zuoshuang “Allen” Xiang
Not in picture:
-- Sirarat Sarntivijai
-- Keerthi S. Sannareddy
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Barry Smith (Buffalo)
Lindsay Cowell (Duke)
Bjoern Peters (La Jolla Institute)
Alan Ruttenberg (Sci. Commons)
Ryan Brinkman (BC, Canada)
Melanie Courtot (BC, Canada)
…
Funding:
NIH-NIAID, GLRCE, NCIBI
University of Michigan