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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