Conceptual Knowledge Discovery in Databases for Drug Combinations Predictions in Malignant Melanoma.

Journal: Studies in health technology and informatics
Published Date:

Abstract

The worldwide incidence of melanoma is rising faster than any other cancer, and prognosis for patients with metastatic disease is poor. Current targeted therapies are limited in their durability and/or effect size in certain patient populations due to acquired mechanisms of resistance. Thus, the development of synergistic combinatorial treatment regimens holds great promise to improve patient outcomes. We have previously shown that a model for in-silico knowledge discovery, Translational Ontology-anchored Knowledge Discovery Engine (TOKEn), is able to generate valid relationships between bimolecular and clinical phenotypes. In this study, we have aggregated observational and canonical knowledge consisting of melanoma-related biomolecular entities and targeted therapeutics in a computationally tractable model. We demonstrate here that the explicit linkage of therapeutic modalities with biomolecular underpinnings of melanoma utilizing the TOKEn pipeline yield a set of informed relationships that have the potential to generate combination therapy strategies.

Authors

  • Kelly Regan
    Department of Biomedical Informatics, The Ohio State University, Columbus, OH.
  • Satyajeet Raje
    Department of Computer Science and Engineering, The Ohio State University, Columbus, OH, USA.
  • Cartik Saravanamuthu
    Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
  • Philip R O Payne
    Institute for Informatics, Data Science and Biostatistics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.