Metastatic Site Prediction in Breast Cancer using Omics Knowledge Graph and Pattern Mining with Kirchhoff’s Law Traversal

Abstract

AbstractPrediction of metastatic sites from the primary site of origin is a impugn task in breast cancer (BRCA). Multi-dimensionality of such metastatic sites - bone, lung, kidney, and brain, using large-scale multi-dimensional Poly-Omics (Transcriptomics, Proteomics and Metabolomics) data of various type, for example, CNV (Copy number variation), GE (Gene expression), DNA methylation, path-ways, and drugs with clinical associations makes classification of metastasis a multi-faceted challenge. In this paper, we have approached the above problem in three steps; 1) Applied Linked data and semantic web to build Poly-Omics data as knowledge graphs and termed them as cancer decision network; 2) Reduced the dimensionality of data using Graph Pattern Mining and explained gene rewiring in cancer decision network by first time using Kirchhoff’s law for knowledge or any graph traversal; 3) Established ruled based modeling to understand the essential -Omics data from poly-Omics for breast cancer progression 4) Predicted the disease’s metastatic site using Kirchhoff’s knowledge graphs as a hidden layer in the graph convolution neural network(GCNN). The features (genes) extracted by applying Kirchhoff’s law on knowledge graphs are used to predict disease relapse site with 91.9% AUC (Area Under Curve) and performed detailed evaluation against the state-of-the-art approaches. The novelty of our approach is in the creation of RDF knowledge graphs from the poly-omics, such as the drug, disease, target(gene/protein), pathways and application of Kirchhoff’s law on knowledge graph to and the first approach to predict metastatic site from the primary tumor. Further, we have applied the rule-based knowledge graph using graph convolution neural network for metastasis site prediction makes the even classification novel.