Bioinformatics, systems biology, host-Brucella interaction, and vaccine research
Our laboratory performs dry-lab (bioinformatics lab) and wet-lab (microbiology and immunology lab) biomedical research
Our bioinformatics research has the following focuses: (1) Ontology development and applications. Dr. He founded and is a primary developer of the Vaccine Ontology (VO) and the Ontology of Adverse Events (OAE). We are also leading or involving the development of several other ontologies. In addition, we have developed many software programs (e.g., OntoFox and Ontobee) that are widely used for ontology reuse, ontology development, and ontology applications. (2) Literature mining, especially ontology-based literature mining. (3) Bayesian network (BN) modeling. BNs can model linear, nonlinear, combinatorial, and stochastic relationships among variables across multiple levels of biological organizations. We have developed new BN algorithms and tools for analysis of gene interaction networks using high throughput gene expression data.
More specific domains of our bioinformatics research include: (1) Vaccine Informatics. We have developed the VIOLIN vaccine database and analysis system. As a part of VIOLIN, we have developed Vaxign, the first web-based publically available vaccine target design tool based on bioinformatics analysis of genome sequences using the strategy of reverse vaccinology. (2) Analysis of host-microbe interactions. We are interested in developing and applying omics and systems biology-based approaches to study the intricate interactions between host (e.g., human and mouse) and microbes (pathogens or bacterial microbiota). (3) Analysis of vaccine and drug adverse event mechanisms. We are interested in developing and applying OAE-based ontology approaches to study the mechanisms of vaccine and drug-induced adverse events.
Our wet-lab research is focused on the study of Brucella, a facultative intracellular bacterium that causes brucellosis, one of the most common zoonotic diseases in the world in humans and a variety of animal species. Our Brucella research has two themes: (1) Analysis of the caspase-2 cell death pathway and its role in Brucella pathogenesis and immunity. Virulent Brucella survives inside macrophages and prevents macrophage cell death, while attenuated rough Brucella strains (e.g., B. abortus cattle vaccine RB51 and B. suis vaccine candidate VTRS1) cannot survive inside macrophages and induce a novel caspase-2-mediated proinflammatory cell death that is different from classical apoptosis or pyroptosis. We coined such a cell death as "caspase-2-mediated pyroptosis". Caspase-2 is critical in regulating cell death, DNA damage, stress, cancer, and microbial infections. Our research aims to elucidate the caspase-2-mediated proinflammatory cell death pathway and its biological effect on microbial pathogenesis, protective immunity, and vaccine development against brucellosis and other diseases. (2) Development of effective and safe Brucella vaccines potentially for human use. We are interested in applying reverse vaccinology and more effective adjuvant strategies for Brucella vaccine research and development.
Racz R, Chung M, Xiang Z, and He Y. Systematic annotation and analysis of "virmugens" - virulence factors whose mutants can be used as live attenuated vaccines. Vaccine. December 6, 2012. DOI: 10.1016/j.vaccine.2012.11.066. PMID: 23219434.
Sarntivijai S, Xiang Z, Shedden KA, Markel H, Omenn GS, Athey BD, and He Y. Ontology-based combinatorial comparative analysis of adverse events associated with killed and live influenza vaccines. PLoS ONE. 2012, 7(11): e49941. PMID: 23209624.
Hur J, Xiang Z, Feldman EL, He Y. Ontology-based Brucella vaccine literature indexing and systematic analysis of gene-vaccine association network. BMC Immunology. 2011 Aug 26; 12(1):49. PMID: 21871085.
Ozgur A, Xiang Z, Radev D, He Y. Mining of vaccine-associated IFN-γ gene interaction networks using the Vaccine Ontology. Journal of Biomedical Semantics. 2011, 2(Suppl 2):S8. PMID: 21624163.
Chen F, Ding X, Ding Y, Xiang Z, Li X, Ghosh D, Schurig GG, Sriranganathan N, Boyle SM, He Y. Proinflammatory caspase-2 mediated macrophage cell death induced by rough attenuated Brucella suis. Infection and Immunity. 2011 Jun;79(6):2460-9. PMID: 21464087.
He Y, Xiang Z, Mobley HLT. Vaxign: the first web-based vaccine design program for reverse vaccinology and an application for vaccine development. Journal of Biomedicine and Biotechnology. 2010;2010:297505. PMID: 20671958.
Hodges AP, Dai D, Xiang Z, Woolf P, Xi C, He Y. Bayesian network expansion identifies new ROS and biofilm regulators. PLoS ONE. 2010 Mar 3;5(3):e9513. PMID: 20209085.
Xiang Z, Todd T, Ku KP, Kovacic BL, Larson CB, Chen F, Hodges AP, Tian Y, Olenzek EA, Zhao B, Colby LA, Rush HG, Gilsdorf JR, Jourdian GW, He Y. VIOLIN: Vaccine Investigation and Online Information Network. Nucleic Acids Research. 2008, Vol. 36, Database issue D923-D928. PMID: 18025042.
Xiang Z, Minter RM, Bi X, Woolf PJ, He Y. miniTUBA: medical inference by network integration of temporal data using Bayesian analysis. Bioinformatics. 2007 Sep 15;23(18):2423-32.
Xiang Z, Tian Y, He Y. PHIDIAS: a pathogen-host interaction data integration and analysis system. Genome Biology. 2007 Jul 30;8(7):R150.