Identifying epigenetically dysregulated pathways from pathway–pathway interaction networks

• Epigenetic mechanisms like DNA Methylation regulate biological pathways.
• A novel framework to capture topological interactions between pathways is proposed.
• Experiments revealed epigenetically dysregulated pathways in various cancers.
• Epigenetic signatures identified can act as robust tumor molecular biomarkers.
• This research fosters recent efforts in Molecular Pathological Epidemiology.

Background: Identification of pathways that show significant difference in activity between disease and control samples have been an interesting topic of research for over a decade. Pathways so identified serve as potential indicators of aberrations in phenotype or a disease condition. Recently, epigenetic mechanisms such as DNA methylation are known to play an important role in altering the regulatory mechanism of biological pathways. It is reasonable to think that a set of genes that show significant difference in expression and methylation interact together to form a network of pathways. Existing pathway identification methods fail to capture the complex interplay between interacting pathways.Results: This paper proposes a novel framework to identify biological pathways that are dysregulated by epigenetic mechanisms. Experiments on four benchmark cancer datasets and comparison with state-of-the-art pathway identification methods reveal the effectiveness of the proposed approach.Conclusion: The proposed framework incorporates both topology and biological relationships of pathways. Comparison with state-of-the-art techniques reveals promising results. Epigenetic signatures identified from pathway interaction networks can help to advance Molecular Pathological Epidemiology (MPE) research efforts by predicting tumor molecular changes.

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