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

Author:

Özgür Arzucan1,Xiang Zuoshuang234,Radev Dragomir R.15,He Yongqun234

Affiliation:

1. Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA

2. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109, USA

3. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA

4. Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA

5. School of Information, University of Michigan, Ann Arbor, MI 48109, USA

Abstract

Interferon-gamma (IFN-γ) regulates various immune responses that are often critical for vaccine-induced protection. In order to annotate the IFN-γ-related gene interaction network from a large amount of IFN-γresearch 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-γ(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-γrelatedness of 56 genes and vaccine development relatedness for 52 genes. This study also generated many new hypotheses worth further experimental studies.

Funder

National Institutes of Health

Publisher

Hindawi Limited

Subject

Health, Toxicology and Mutagenesis,Genetics,Molecular Biology,Molecular Medicine,General Medicine,Biotechnology

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