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He Lab Overview: Systems Biology Studies of Host-pathogen Interactions and Vaccines

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

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He Lab Overview: Systems Biology Studies of Host-pathogen Interactions and Vaccines

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  1. He Lab Overview: Systems Biology Studies of Host-pathogen Interactions and Vaccines (Workshop on Data, Text, Web & Social Network Mining) Yongqun “Oliver” HeUnit for Laboratory Animal MedicineDepartment of Microbiology and ImmunologyCenter for Computational Medicine and Bioinformatics University of Michigan Medical SchoolAnn 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 Caspase-2 mediated cell death of macrophages induced by Brucella vaccines but not by virulent Brucella strains Brucella vaccine-infected macrophages from Caspase-2 knockout mice Annexin V-PI fluorescence Light microscopy

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

  5. 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: …)

  6. 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

  7. 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

  8. 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

  9. Vaxign: Vaccine Design--the 1st web-based vaccine design system based on reverse vaccinologyhttp://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 domain • Allow computers to understand and analyze data • Support computer-assisted reasoning http://www.violinet.org/vaccineontology

  11. VO-based literature mining • VO-based SciMiner: to index vaccine literature based on VO terms. • Joint work with Junguk Hur, Eva Feldman • VO-based literature discover of IFNG interaction networks • Joint work with Arzucan Özgür, Dragomir R. Radev

  12. Acknowledgements 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 • 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) • … * ** *** * Dr. Fang Chen ** Andrew Hodges ***Zuoshuang “Allen” Xiang Not in picture: -- Sirarat Sarntivijai -- Keerthi S. Sannareddy Funding: NIH-NIAID, GLRCE, NCIBI University of Michigan

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