A novel strategy for integrating gene expression profiles derived from multiple publicly available datasets highlights novel hub genes and pathways in mouse models of allergic asthma
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1
San Raffaele Scientific Institute, Center for Translational Genomics and Bioinformatics, Italy
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2
University of Vienna, Department of Dermatology, Austria
There are 30 studies of gene expression profiling of lungs from mice with allergic asthma, which shed new light on the molecular mechanisms of disease, but the experimental designs between them differ. Nevertheless, relevant genes and pathways underlying disease pathogenesis may emerge from the integration of these datasets. From 12 publically available datasets, we selected 6 for meta-analysis on the basis of the microarray platform and in vivo experimental protocol. Our strategy was to combine a top down pathwaycentered and a bottom up genecentered analyses. The first approach consisted of selecting asthmaspecific pathways from a combination of ‘enriched biological terms’ in each individual study. Whereas, secondly, we combined differentially expressed genes from individual datasets to create a gene list. From 22,690 genes and 131 samples, we obtained a core-network of more than 300 interconnected genes unraveling known (STAT1, JAK2) and unknown hubs (PU.1, CDK1). Additionally, we successfully selected known and unknown disease-related pathways, such as Tcell activation during an immune response, Bcell mediated immunity, phagocytosis and complement activation. The power of this strategy is the possibility of uncovering key molecules underlying disease pathogenesis utilizing datasets derived from disparate experiments
Keywords:
Asthma,
Gene Expression,
Network analysis,
Meta-analysis,
pathway analysis
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Riba
M,
Garcia Manteiga
JM,
Bosniak
B,
Epstein
M and
Stupka
E
(2013). A novel strategy for integrating gene expression profiles derived from multiple publicly available datasets highlights novel hub genes and pathways in mouse models of allergic asthma.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00881
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Received:
20 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Michela Riba, San Raffaele Scientific Institute, Center for Translational Genomics and Bioinformatics, Milano, Italy, riba.michela@hsr.it