1. 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

2. Overview

3. 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. Brucella vaccine- infected macrophages from wild type mice Brucella vaccine-infected macrophages from Caspase-2 knockout mice Light microscopy Annexin V-PI fluorescence Caspase-2 mediated cell death of macrophages induced by Brucella vaccines but not by virulent Brucella strains

4. miniTUBA: dynamic Bayesian network (BN) analysis system -- http://www.minituba.org/http://www.minituba.org/ Experimentally Confirmed: Casp2, Tnf, Nf-kb, Casp1 Predicted network of Brucella- induced macrophage cell death miniTUBA: A pipeline – - data input, - missing data prediction, - dynamic BN calculation, - prediction of future event, - output visualization

5. BN+1: Bayesian network expansion -- Iteratively test all possible genes Confirmed BN+1 identified new ROS and biofilm regulators (PMID: …) BN+1: find pathway hidden factors

6. Limix: Literature mining & curation system -- http://www.limix.orghttp://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

7. PHIDIAS: Pathogen-Host Interaction Data Integration and Analysis System -- http://www.phidias.us/http://www.phidias.us/ Focus: PHI – Pathogen-host interaction Statistics: ~60 pathogens, >700 genomes Model organism: Brucella

8. VIOLIN: Vaccine Investigation and Online Information Network -- http://www.violinet.orghttp://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

9. Vaxign: Vaccine Design --the 1 st web-based vaccine design system based on reverse vaccinology http://www.violinet.org/vaxign http://www.violinet.org/vaxign Reverse vaccinology: predict vaccine targets first from bioinformatics analysis of genomes Applications: UPEC, Brucella, Francisella, …

10. VO: Vaccine Ontology -- a community effort Vaccine Ontology (VO): Controlled vocabulary of terms and relations (“ontology”) in the vaccine domainVaccine Ontology (VO): Controlled vocabulary of terms and relations (“ontology”) in the vaccine domain Allow computers to understand and analyze dataAllow computers to understand and analyze data Support computer-assisted reasoningSupport computer-assisted reasoning http://www.violinet.org/vaccineontology

11. 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

12. Acknowledgements Funding: NIH-NIAID, GLRCE, NCIBI University of Michigan He Laboratory / U of Michigan (UM)UM Collaborators: Peter Woolf Brian Athey Harry Mobley Arzucan Özgür, Dragomir R. Radev Junguk Hur, Eva Feldman Dongjuan Dai, Chuanwu Xi * Dr. Fang Chen ** Andrew Hodges *** Zuoshuang “Allen” Xiang Not in picture: -- Sirarat Sarntivijai -- Keerthi S. Sannareddy *** * ** Vaccine Ontology Collaborators: Barry Smith (Buffalo) Lindsay Cowell (Duke) Bjoern Peters (La Jolla Institute) Alan Ruttenberg (Sci. Commons) Ryan Brinkman (BC, Canada) Melanie Courtot (BC, Canada) …