Mathematical Modeling and Deconvolution of Molecular Heterogeneity Identifies Novel Subpopulations in Complex Tissues.

Tissue heterogeneity is both a major confounding factor and an underexploited information source. While a handful of reports have demonstrated the potential of supervised methods to deconvolve tissue heterogeneity, these approaches require a priori information on the marker genes or composition of known subpopulations. To address the critical problem of the absence of validated marker genes for many (including novel) subpopulations, we develop a novel unsupervised deconvolution method, Convex Analysis of Mixtures (CAM), within a well-grounded mathematical framework, to dissect mixed gene expressions in heterogeneous tissue samples. To facilitate the utility of this method, we implement an R-Java CAM package that provides comprehensive analytic functions and graphic user interface (GUI).