A bioinformatics pipeline to uncover regulatory modules and their condition-specific regulators in human monocyte-to-macrophages differentiation and polarization
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1
University of Modena and Reggio Emilia, Center for Genome Research, Department of Life Sciences, Italy
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2
National Research Council (CNR), Pisa, Institute of Biomedical Technologies (ITB), Italy
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3
National Research Council (CNR), Milan, Institute of Biomedical Technologies (ITB), Italy
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4
University of Milan, Department of Medical Biotechnology and Translational Medicine, Italy
In healthy organisms, inflammation is the first line of defense against infections and other damage. Monocytes and macrophages are key players of this process. Since a deregulation of the activity of these cells is at the basis of several pathological conditions, elucidating the molecular mechanisms of monocyte/macrophage activation represents a major step to study inflammatory disorders and, eventually, develop new therapeutic strategies. However, these mechanisms and their interplay during monocyte/macrophage activation and M1/M2 polarization remain poorly characterized. Here we report the application of computational methods to reconstruct gene regulatory networks and decipher transcriptional modules in an in vitro model of physiological inflammation. Specifically, gene expression profiles of human blood monocytes, from normal healthy donors and exposed to combinations of factors reproducing normal inflammatory conditions, have been monitored during a time course of 48 hours and transcriptional data analyzed using an ad-hoc bioinformatics pipeline aimed at reconstructing gene regulatory modules. The computational process starts with the identification of clusters of co-regulated genes whose expression changes during the time course. Through enrichment analysis and scanning analysis of transcription factor (TF) binding site motifs, we identified subsets of inflammation related genes and TFs that can be considered as process controllers and, thus, further used as candidates to reconstruct regulatory modules. The bioinformatics analysis identified several member of the interleukin-1 family as master regulators of specific regulatory modules linked to the inflammation process.
Keywords:
Gene Regulatory Networks,
Transcriptional regulation,
physiological inflammation,
Macrophages,
Macrophage Differentiation and Polarization
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Mazza
E,
Italiani
P,
Valsoni
S,
Cifola
I,
Boraschi
D,
Battaglia
C and
Bicciato
S
(2013). A bioinformatics pipeline to uncover regulatory modules and their condition-specific regulators in human monocyte-to-macrophages differentiation and polarization.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01058
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Received:
30 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Emilia Maria Cristina Mazza, University of Modena and Reggio Emilia, Center for Genome Research, Department of Life Sciences, Modena, Italy, emilia.mazza@unimore.it