Inferring cell cycle feedback regulation from gene expression data

Authors:
Fulvia Ferrazzi;Felix B. Engel;Erxi Wu;Annie P. Moseman;Isaac S. Kohane;Riccardo Bellazzi;Marco F. Ramoni
Affiliations:
Dipartimento di Informatica e Sistemistica, Universití degli Studi di Pavia, Pavia, Italy and Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, ...;Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany;Department of Pharmaceutical Sciences, North Dakota State University, Fargo, USA;Immunology Program, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, USA;Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, USA;Dipartimento di Informatica e Sistemistica, Universití degli Studi di Pavia, Pavia, Italy;Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, USA
Venue:
Journal of Biomedical Informatics
Year:
2011

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Abstract

Feedback control is an important regulatory process in biological systems, which confers robustness against external and internal disturbances. Genes involved in feedback structures are therefore likely to have a major role in regulating cellular processes. Here we rely on a dynamic Bayesian network approach to identify feedback loops in cell cycle regulation. We analyzed the transcriptional profile of the cell cycle in HeLa cancer cells and identified a feedback loop structure composed of 10 genes. In silico analyses showed that these genes hold important roles in system's dynamics. The results of published experimental assays confirmed the central role of 8 of the identified feedback loop genes in cell cycle regulation. In conclusion, we provide a novel approach to identify critical genes for the dynamics of biological processes. This may lead to the identification of therapeutic targets in diseases that involve perturbations of these dynamics.