Regulation of Epithelial–Mesenchymal Transition Pathway and Artificial Intelligence-Based Modeling for Pathway Activity Prediction.

Simple Summary: Molecular network pathways are activated or inactivated under various conditions. Previously, we revealed that epithelial–mesenchymal transition (EMT) is a feature of diffuse-type gastric cancer. Here, we modeled the activation states of EMT in the development pathway using molecular pathway images and artificial intelligence (AI). The regulation of EMT in the development pathway was activated in diffuse-type gastric cancer (GC) and inactivated in intestinal-type GC. AI modeling with molecular pathway images generated a highly accurate Elastic-Net Classifier models that was validated with 10 additional activated and 10 inactivated pathway images. Because activity of the epithelial–mesenchymal transition (EMT) is involved in anti-cancer drug resistance, cancer malignancy, and shares some characteristics with cancer stem cells (CSCs), we used artificial intelligence (AI) modeling to identify the cancer-related activity of the EMT-related pathway in datasets of gene expression. We generated images of gene expression overlayed onto molecular pathways with Ingenuity Pathway Analysis (IPA). A dataset of 50 activated and 50 inactivated pathway images of EMT regulation in the development pathway was then modeled by the DataRobot Automated Machine Learning platform. The most accurate models were based on the Elastic-Net Classifier algorithm. The model was validated with 10 additional activated and 10 additional inactivated pathway images. The generated models had false-positive and false-negative results. These images had significant features of opposite labels, and the original data were related to Parkinson's disease. This approach reliably identified cancer phenotypes and treatments where EMT regulation in the development pathway was activated or inactivated thereby identifying conditions where therapeutics might be applied or developed. As there are a wide variety of cancer phenotypes and CSC targets that provide novel insights into the mechanism of CSCs' drug resistance and cancer metastasis, our approach holds promise for modeling and simulating cellular phenotype transition, as well as predicting molecular-induced responses. [ABSTRACT FROM AUTHOR]