SEPIRA

"SEPIRA" (Systems-Epigenomics Inference of Regulatory Activity) is a systems-epigenomics algorithm to infer the regulatory activity of transcription factors (TFs) in lung carcinogenesis from messenger RNA expression or DNA methylation (DNAm) profiles. Developed against the backdrop of identifying molecular alterations associated with smoking in normal and precursor lung cancer cells, SEPIRA leverages a vast RNA-sequencing expression compendium to provide insights into the landscape of lung-specific TF binding activity during the onset and progression of lung cancer.

A key finding from the application of SEPIRA is the preferential inactivation of lung-specific TFs in both lung and precursor lung cancer lesions. This observation can be made using only DNAm data. Among the inactivated regulatory factors identified are AHR (aryl hydrocarbon-receptor), which is crucial for a healthy immune response in the lung epithelium, and FOXJ1, a TF that supports the growth of airway cilia for adequate clearance of carcinogens from the lung airway epithelium.