Distinguishing Cell Phenotype Using Cell Epigenotype
This work addresses the fundamental biophysical challenge of linking microscopic observations to macroscopic behavior in cell biology, representing an incremental step toward model-independent control strategies.
The authors tackled the problem of predicting cell type from macromolecular data despite human tissue diversity and data limitations, achieving this by applying k-nearest-neighbors after projecting data onto eigenvectors of correlation matrices from gene expression or chromatin conformation observations.
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 impact cell type, thereby supporting the cell type attractor hypothesis and representing the first step toward model-independent control strategies in biological systems.