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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 426479, 13 pages
Methodology Report

Literature-Based Discovery of IFN- and Vaccine-Mediated Gene Interaction Networks

1Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA
2Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
3Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA
4Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
5School of Information, University of Michigan, Ann Arbor, MI 48109, USA

Received 1 November 2009; Accepted 8 March 2010

Academic Editor: Rino Rappuoli

Copyright © 2010 Arzucan Özgür et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Interferon-gamma (IFN-) regulates various immune responses that are often critical for vaccine-induced protection. In order to annotate the IFN--related gene interaction network from a large amount of IFN- research reported in the literature, a literature-based discovery approach was applied with a combination of natural language processing (NLP) and network centrality analysis. The interaction network of human IFN- (Gene symbol: IFNG) and its vaccine-specific subnetwork were automatically extracted using abstracts from all articles in PubMed. Four network centrality metrics were further calculated to rank the genes in the constructed networks. The resulting generic IFNG network contains 1060 genes and 26313 interactions among these genes. The vaccine-specific subnetwork contains 102 genes and 154 interactions. Fifty six genes such as TNF, NFKB1, IL2, IL6, and MAPK8 were ranked among the top 25 by at least one of the centrality methods in one or both networks. Gene enrichment analysis indicated that these genes were classified in various immune mechanisms such as response to extracellular stimulus, lymphocyte activation, and regulation of apoptosis. Literature evidence was manually curated for the IFN- relatedness of 56 genes and vaccine development relatedness for 52 genes. This study also generated many new hypotheses worth further experimental studies.