Evaluation of Archetypal Analysis and Manifold Learning for Phenotyping of Acute Kidney Injury

Disease subtyping has been a critical aim of precision and personalized medicine. With the potential to improve patient outcomes, unsupervised and semi-supervised methods for determining phenotypes of subtypes have emerged with a recent focus on matrix and tensor factorization. However, interpretability of proposed models is debatable. Principal component analysis (PCA), a traditional method of dimensionality reduction, does not impose non-negativity constraints. Thus coefficients of the principal components are, in cases, difficult to translate to real physical units. Non-negative matrix factorization (NMF) constrains the factorization to positive numbers such that representative types resulting from the factorization are additive. Archetypal analysis (AA) extends this idea and seeks to identify pure types, archetypes, at the extremes of the data from which all other data can be expressed as a convex combination, or by proportion, of the archetypes. Using AA, this study sought to evaluate the sufficiency of AKI staging criteria through unsupervised subtyping. Archetype analysis failed to find a direct 1:1 mapping of archetypes to physician staging and also did not provide additional insight into patient outcomes. Several factors of the analysis such as quality of the data source and the difficulty in selecting features contributed to the outcome. Additionally, after performing feature selection with lasso across data subsets, it was determined that current staging criteria is sufficient to determine patient phenotype with serum creatinine at time of diagnosis to be a necessary factor.