Priority-Elastic net for binary disease outcome prediction based on multi-omics data

Abstract

Abstract Background High-dimensional omics data integration has emerged as a prominent avenue within the healthcare industry, presenting substantial potential to improve predictive models. However, the data integration process faces several challenges, including data heterogeneity, priority sequence in which data blocks are prioritized for rendering predictive information contained in multiple blocks, assessing the flow of information from one omics level to the other and multicollinearity. Methods We propose the Priority-Elastic net algorithm, a hierarchical regression method extending Priority-Lasso for the binary logistic regression model by incorporating a priority order for blocks of variables while fitting Elastic-net models sequentially for each block. The fitted values from each step are then used as an offset in the subsequent step. Additionally, we considered the adaptive elastic-net penalty within our priority framework to compare the results. Results The Priority-Elastic net and Priority-Adaptive Elastic net algorithms were evaluated on a brain tumor dataset available from The Cancer Genome Atlas (TCGA), accounting for transcriptomics, proteomics, and clinical information measured over two glioma types: Lower-grade glioma (LGG) and glioblastoma (GBM). Conclusion Our findings suggest that the Priority-Elastic net is a highly advantageous choice for a wide range of applications. It offers moderate computational complexity, flexibility in integrating prior knowledge while introducing a hierarchical modeling perspective, and, importantly, improved stability and accuracy in predictions, making it superior to the other methods discussed. This evolution marks a significant step forward in predictive modeling, offering a sophisticated tool for navigating the complexities of multi-omics datasets in pursuit of precision medicine’s ultimate goal: personalized treatment optimization based on a comprehensive array of patient-specific data. This framework can be generalized to time-to-event, Cox proportional hazards regression and multicategorical outcomes. A practical implementation of this method is available upon request in R script, complete with an example to facilitate its application.

Keywords

• Adaptive-Elastic net
• Elastic-net
• High-dimensional data
• Logistic regression
• Multi-omics data
• Priority-Lasso