Trajectories, bifurcations, and pseudo-time in large clinical datasets: applications to myocardial infarction and...

Large observational clinical datasets are becoming increasingly available for mining associations between various disease traits and administered therapy. These datasets can be considered as representations of the landscape of all possible disease conditions, in which a concrete disease state develops through stereotypical routes, characterized by "points of no return" and "final states" (such as lethal or recovery states). Extracting this information directly from the data remains challenging, especially in the case of synchronic (with a short-term follow-up) observations.

Here we suggest a semi-supervised methodology for the analysis of large clinical datasets, characterized by mixed data types and missing values, through modeling the geometrical data structure as a bouquet of bifurcating clinical trajectories. The methodology is based on application of elastic principal graphs, which can address simultaneously the tasks of dimensionality reduction, data visualization, clustering, feature selection, and quantifying the geodesic distances (pseudo-time) in partially ordered sequences of observations. The methodology allows a patient to be positioned on a particular clinical trajectory (pathological scenario) and the degree of progression along it to be characterized with a qualitative estimate of the uncertainty of the prognosis. We developed a tool ClinTrajan for clinical trajectory analysis implemented in the Python programming language. We test the methodology in 2 large publicly available datasets: myocardial infarction complications and readmission of diabetic patients data.

Our pseudo-time quantification-based approach makes it possible to apply the methods developed for dynamical disease phenotyping and illness trajectory analysis (diachronic data analysis) to synchronic observational data.