Detecting coordinated regulations of pathways by higher logic analysis

Non-small cell lung cancer (NSCLC) is a malignant tumor, and contains three major subtypes which are difficult to be distinguished at early stages of NSCLC. Many pathways work together to perform certain functions in cells. One might expect the high level of co-appearance or repression of pathways to distinguish different subtypes of NSCLC. However, it is difficult to detect coordinated regulations of pathways by existing methods. In our work, the coordinated regulations of pathways are detected using modified higher logic analysis of gene expression data. Specifically, we identify the genes whose regulation obeys a logic function by the modified higher logic analysis, which focuses on the relationships among the gene triplets that are not evident when genes are examined in a pairwise fashion. Then, the relationships among genes are mapped to pathways to predict the coordinated regulated relationships among pathways. By comparing coordinated regulations of pathways, we find that the regulation patterns of pathways which are associated with cell death are different in three subtypes of NSCLC. This method allows us to uncover co-appearance or repression of pathways in high level, and it has a potential to distinguish the subtypes for complex diseases.