Clinical trajectories estimated from bulk tumoral molecular profiles using elastic principal trees

Clinical trajectory is a clinically relevant sequence of ordered patient phenotypes representing consecutive states of a developing disease and leading to some final state. Extracting trajectories from large scale medical data is of great interest for dynamical phenotyping of various diseases but remains a challenge for machine learning methods, especially in the case of synchronic (with short follow up) observations. Here we describe an approach for trajectory-based analysis of cancer data using elastic principal trees and test it on a large collection of molecular tumoral profiles for breast cancer. We show that the disease progress quantified with pseudotime (the geodesic distance from the root) along a particular trajectory can serve as a significant prognostic factor, not redundant with gene expression-based predictors. We conclude that application of the elastic principal trees to transcriptomic data can be of interest for clinical applications.