Distinguishing cell phenotype using cell epigenotype

The relationship between microscopic observations and macroscopic behavior is a fundamental open question in biophysical systems. Here, we develop a unified approach that—in contrast with existing methods—predicts cell type from macromolecular data even when accounting for the scale of human tissue diversity and limitations in the available data. We achieve these benefits by applying a k-nearest-neighbors algorithm after projecting our data onto the eigenvectors of the correlation matrix inferred from many observations of gene expression or chromatin conformation. Our approach identifies variations in epigenotype that affect cell type, thereby supporting the cell-type attractor hypothesis and representing the first step toward model-independent control strategies in biological systems.