A0574
Title: A unified mediation analysis framework for integrative cancer proteogenomics with clinical outcomes
Authors: Min Jin Ha - Yonsei University (Korea, South) [presenting]
Abstract: Multilevel molecular profiling of tumours and integrative analysis with clinical outcomes have enabled a deeper characterization of cancer treatment. Mediation analysis has emerged as a promising statistical tool to identify and quantify the intermediate mechanisms by which a gene affects an outcome. However, existing methods lack a unified approach to handle various types of outcome variables, making them unsuitable for high-throughput molecular profiling data with highly interconnected variables. A general mediation analysis framework is developed for proteogenomic data that includes multiple exposures and multivariate mediators on various effects scales as appropriate for continuous, binary and survival outcomes. The estimation method avoids imposing constraints on model parameters, such as the rare disease assumption while accommodating multiple exposures and high-dimensional mediators. Using kidney renal clear cell carcinoma proteogenomic data, it is identified genes that are mediated by proteins and the underlying mechanisms on various survival outcomes that capture short- and long-term disease-specific clinical characteristics.
