PLASMA: Partial LeAst Squares for Multiomics Analysis

Background/Objectives: Recent growth in the number and applications of high-throughput "omics" technologies has created a need for better methods to integrate multiomics data. Much progress has been made in developing unsupervised methods, but supervised methods have lagged behind. Methods: Here we present the first algorithm, PLASMA, that can learn to predict time-to-event outcomes from multiomics data sets, even when some samples have only been assayed on a subset of the omics data sets. PLASMA uses two layers of existing partial least squares algorithms to first select components that covary with the outcome and then construct a joint Cox proportional hazards model. Results: We apply PLASMA to the stomach adenocarcinoma (STAD) data from The Cancer Genome Atlas. We validate the model both by splitting the STAD data into training and test sets and by applying them to the subset of esophageal cancer (ESCA) containing adenocarcinomas. We use the other half of the ESCA data, which contains squamous cell carcinomas dissimilar to STAD, as a negative comparison. Our model successfully separates both the STAD test set (p = 2.73 x 10-8) and the independent ESCA adenocarcinoma data (p = 0.025) into high-risk and low-risk patients. It does not separate the negative comparison data set (ESCA squamous cell carcinomas, p = 0.57). The performance of the unified multiomics model is superior to that of individually trained models and is also superior to an unsupervised method (Multi-Omics Factor Analysis; MOFA), which finds latent factors to be used as putative predictors in a post hoc survival analysis. Conclusions: Many of the factors that contribute strongly to the PLASMA model can be justified from the biological literature.